botanical research article

The Botanical Review

For more than half a century, The Botanical Review has been a leading international journal noted for its in-depth articles on a broad spectrum of botanical fields. Systematics, phytogeography, cladistics, evolution, physiology, ecology, morphology, paleobotany, and anatomy are but a few of the many subjects that have been covered. The Botanical Review draws together outstanding scientists in the field, synthesizes the current knowledge about a specific subject, and promotes the advancement of botany by indicating the gaps in our knowledge and providing new outlooks on the topic.

• Barbara A. Ambrose

Societies and partnerships

Latest issue

Volume 90, Issue 2

Latest articles

A typological and morphological analysis of the pleurothallidinae (orchidaceae) inflorescences.

• Gustavo Rojas-Alvarado
• Adam Karremans

Macrofungal Species Richness and Composition of Acre State, Amazon, Brazil: State of the Art

• Márcia de Araújo Teixeira-Silva
• Chirley Gonçalves da Silva
• Marcos Silveira

An Overview of Reproductive Allocation and Reproductive Costs in Bryophytes: Challenges and Prospects

• Wagner Luiz dos Santos
• Kátia Cavalcanti Pôrto
• Fábio Pinheiro

Polyembryony: A Potential Horticultural Trait, Reveals Complex Mechanism, Role of Molecular Markers and their Application in Fruit Crops

• Gurupkar Singh Sidhu
• Prashant Mohanpuria
• Harmanpreet Kaur

Computer Vision for Plant Disease Recognition: A Comprehensive Review

• Hanxiang Wang
• Tan N. Nguyen

Journal updates

Co-publisher information, journal information.

• Astrophysics Data System (ADS)
• Biological Abstracts
• CAB Abstracts
• Current Contents/Agriculture, Biology & Environmental Sciences
• Google Scholar
• Japanese Science and Technology Agency (JST)
• OCLC WorldCat Discovery Service
• Science Citation Index Expanded (SCIE)
• TD Net Discovery Service
• UGC-CARE List (India)

Rights and permissions

Editorial policies

© The New York Botanical Garden

• Find a journal
• Publish with us
• Track your research

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

• View all journals
• Explore content
• About the journal
• Publish with us
• Sign up for alerts
• Published: 01 June 2015

Expanding the role of botanical gardens in the future of food

• A. J. Miller 1 , 2 ,
• A. Novy 3 , 4 ,
• J. Glover 5 ,
• E. A. Kellogg 6 ,
• J. E. Maul 7 ,
• P. Raven 2 &
• P. Wyse Jackson 2 , 8  

Nature Plants volume  1 , Article number:  15078 ( 2015 ) Cite this article

1438 Accesses

19 Citations

30 Altmetric

Metrics details

• Agroecology
• Agriculture
• Natural variation in plants

Consistent with their historical focus on the functional utility of plants, botanical gardens have an important opportunity to help ensure global food and ecosystem security by expanding their living collections, research and education programmes to emphasize agriculture and its impacts.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Using botanical resources to select wild forage legumes for domestication in temperate grassland agricultural systems

• Brooke Micke
•  &  David Parsons

Agronomy for Sustainable Development Open Access 21 December 2022

Access options

Subscribe to this journal

Receive 12 digital issues and online access to articles

111,21 € per year

only 9,27 € per issue

Buy this article

• Purchase on Springer Link
• Instant access to full article PDF

Prices may be subject to local taxes which are calculated during checkout

Millennium Ecosystem Assessment Ecosystems and Human Well-being: Biodiversity Synthesis (World Resources Institute, 2005).

Foley, J. A. et al . Nature 478 , 337–342 (2011).

Article   CAS   Google Scholar  

The State of Food Insecurity in the World 2014. Strengthening the Enabling Environment for Food Security and Nutrition 14 (FAO, IFAD and WFP, 2014).

World Population Prospects: The 2012 Revision, Key Findings and Advance Tables Working Paper No. ESA/P/WP.227 (UN Department of Economic and Social Affairs, Population Division, 2013).

Ballyntyne, R., Packer, J. & Hughes, K. Tourism Manage. 29 , 439–444 (2008).

Article   Google Scholar  

De Koning, J. in The Botanical Garden of Padua 1545–1995 (ed. Minelli, A. ) Ch. 2 (Marsilio Editori, 1995).

Google Scholar  

Brockway, L. H. Science and Colonial Expansion: The Role of the British Royal Botanical Garden (Yale Univ. Press, 2002).

Britton, N. L. Science 4 , 284–293 (1896).

Blakeselee, A. F. Science 31 , 685–688 (1910).

Nabhan, G. P. The fatherland of apples. Orion magazine (May/June 2008)

Khoury, C. K. et al . Proc. Natl Acad. Sci. USA 111 , 4001–4006 (2014).

High Level Expert Forum — How to Feed the World in 2050 (FAO, 2009).

Food supply, Crops Primary Equivalent (FAOSTAT) (FAO, accessed 17 February 2011); http://go.nature.com/ZlMzj4

Nationwide Surveys Reveal Disconnect Between Americans and their Food (US Farmers and Ranchers Alliance Food Dialogues, 2011); http://go.nature.com/U71xsR

Cavigelli, M. A., Maul, J. E. & Szlavecz, K. in Soil Ecology and Ecosystem Services 1st edn (eds Wall, D. H. et al .) 337–356 Oxford Univ. Press, 2012).

Book   Google Scholar  

Download references

Author information

Authors and affiliations.

Department of Biology, Saint Louis University, St. Louis, 63103, Missouri, USA

A. J. Miller

Missouri Botanical Garden, St. Louis, 63110, Missouri, USA

A. J. Miller, P. Raven & P. Wyse Jackson

United States Botanic Garden, 20024, Washington DC, USA

Botany Department, Smithsonian Institution National Museum of Natural History, 20560, Washington DC, USA

United States Agency for International Development, 20004, Washington DC, USA

Donald Danforth Plant Science Center, St. Louis, 63132, Missouri, USA

E. A. Kellogg

United States Department of Agriculture, Agricultural Research Service, Sustainable Agricultural Systems Laboratory, Beltsville, 20705, Maryland, USA

Department of Biology, Washington University, St. Louis, 63130, Missouri, USA

P. Wyse Jackson

You can also search for this author in PubMed   Google Scholar

Corresponding authors

Correspondence to A. J. Miller or A. Novy .

Rights and permissions

Reprints and permissions

About this article

Cite this article.

Miller, A., Novy, A., Glover, J. et al. Expanding the role of botanical gardens in the future of food. Nature Plants 1 , 15078 (2015). https://doi.org/10.1038/nplants.2015.78

Download citation

Published : 01 June 2015

DOI : https://doi.org/10.1038/nplants.2015.78

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

This article is cited by

• David Parsons

Agronomy for Sustainable Development (2023)

Botanical gardens as valuable resources in plant sciences

• Leila Faraji
• Mojtaba Karimi

Biodiversity and Conservation (2022)

Botanical gardens as key resources and hazards for biosecurity

• Mesfin Wondafrash
• Michael J. Wingfield

Biodiversity and Conservation (2021)

An Ethnobotanical Study of the Genus Elymus1

• Emma S. Frawley
• Claudia Ciotir
• Allison J. Miller

Economic Botany (2020)

Quick links

• Explore articles by subject
• Guide to authors
• Editorial policies

Sign up for the Nature Briefing: Anthropocene newsletter — what matters in anthropocene research, free to your inbox weekly.

Botanical Studies

Featured articles

Morphology, mating system and taxonomy of Volvox africanus (Volvocaceae, Chlorophyceae) from Thailand

Genetic analysis toward more nutritious barley grains for a food secure world

• Most accessed
• Collections

C amellia neriifolia and Camellia ilicifolia (Theaceae) as separate species: evidence from morphology, anatomy, palynology, molecular systematics

Authors: Zhaohui Ran, Zhi Li, Xu Xiao and Ming Tang

An independent Taiwanese lineage of powdery mildew on the endemic host species Koelreuteria henryi

Authors: Yu-Wei Yeh and Roland Kirschner

New perspectives, additions, and amendments to plant endemism in a North African flora

Authors: Monier Abd El-Ghani, Hasnaa Hosni, Eman Shamso and Faten Ellmouni

Phylogenomics identifies parents of naturally occurring tetraploid bananas

Authors: Yu-En Lin, Hui-Lung Chiu, Chung-Shien Wu and Shu-Miaw Chaw

Evaluating local plant species for effective fall armyworm management strategies in Taiwan

Authors: Yuan-Ching Tsai, Pei-Qi Luo, Chang-Lin Sung, Yi Li, Fang-Yu Hu, Chih-Lu Wang, Yi-Ning Chen, Ju-Hsin Hsu, Chien-En Liao, Shyh-Rong Chang and Wen-Po Chuang

Most recent articles RSS

View all articles

Occurrence, types and distribution of calcium oxalate crystals in leaves and stems of some species of poisonous plants

Authors: Sevil Tütüncü Konyar, Necla Öztürk and Feruzan Dane

How plants cope with heavy metals

Authors: Katrin Viehweger

Lead heavy metal toxicity induced changes on growth and antioxidative enzymes level in water hyacinths [ Eichhornia crassipes (Mart.)]

Authors: Srinivasan Malar, Sahi Shivendra Vikram, Paulo JC Favas and Venkatachalam Perumal

Study on the effect of magnetic field treatment of newly isolated Paenibacillus sp.

Authors: Jie Li, Yanli Yi, Xilei Cheng, Dageng Zhang and Muhammad Irfan

Effects of yam dioscorin interventions on improvements of the metabolic syndrome in high-fat diet-induced obese rats

Authors: Shen-Liang Shih, Yin-Shiou Lin, Shyr-Yi Lin and Wen-Chi Hou

Most accessed articles RSS

Special issue Taxonomic and ecological studies on Ascomycota, with emphasis on xylariaceous fungi - A special issue dedicated to Prof. Jack D. Rogers Edited by Yu-Ming Ju and Julia Kerrigan

Thematic series Orchid conservation Guest edited by Yung-I Lee

Announcing the launch of In Review

Botanical Studies , in partnership with Research Square, is now offering  In Review.  Authors choosing this free optional service will be able to:

• Share their work with fellow researchers to read, comment on, and cite even before publication
• Showcase their work to funders and others with a citable DOI while it is still under review
• Track their manuscript - including seeing when reviewers are invited, and when reports are received 

Featured article collections

Taxonomic and ecological studies on Ascomycota, with emphasis on xylariaceous fungi—A special issue dedicated to Prof. Jack D. Rogers Edited by Yu-Ming Ju and Julia Kerrigan

Orchid conservation Guest edited by Yung-I Lee

Editorial Team

Editor-in-chief.

Senior Editors

Dr. Pi-Fang Chang, Department of Plant Pathology, National Chung Hsing Universiy, Taiwan Dr. Hong-yong Fu, Institute of Plant and Microbial Biology, Academia Sinica, Taiwan Dr. Chih-Horng Kuo, Institute of Plant and Microbial Biology, Academia Sinica, Taiwan Dr. Cheng-Ruei Lee, Institute of Ecology and Evolutionary Biology, National Taiwan University, Taiwan Dr. Shih-Long Tu, Institute of Plant and Microbial Biology, Academia Sinica, Taiwan

Aims and scope

Botanical Studies is an open access journal that encompasses all aspects of botany, including but not limited to taxonomy, morphology, development, genetics, evolution, reproduction, systematics, and biodiversity of all plant groups, algae, and fungi. The journal is affiliated with the Institute of Plant and Microbial Biology, Academia Sinica, Taiwan.

Society affiliation

Why do some trees lose their leaves and others don’t? The Conversation’s Curious Kids podcast

Eloise Stevens , The Conversation

Digging into the colonial roots of gardening

Vinita Srivastava , The Conversation and Ateqah Khaki , The Conversation

Curious Kids: why do trees have bark?

Gregory Moore , The University of Melbourne

Cranberries can bounce, float and pollinate themselves: The saucy science of a Thanksgiving classic

Serina DeSalvio , Texas A&M University

Take a break from your screen and look at plants − botanizing is a great way to engage with life around you

Jacob S. Suissa , University of Tennessee and Ben Goulet-Scott , Harvard University

French botanist Théodore Leschenault travelled to Australia in 1800-1803 . His recently recovered journal contains a wealth of intriguing information

Paul Gibbard , The University of Western Australia

Why does grass grow more slowly in winter?

Colonialism has shaped scientific plant collections around the world – here’s why that matters

Daniel Park , Purdue University

The world’s first flowers were pollinated by insects

Ruby E. Stephens , Macquarie University ; Hervé Sauquet , UNSW Sydney ; Lily Dun , UNSW Sydney ; Rachael Gallagher , Western Sydney University , and Will Cornwell , UNSW Sydney

Native raspberries, limes and geraniums: how did these curious plants end up in Australia?

Decolonize your garden: This long weekend, dig into the complicated roots of gardening — Listen

Learn to think like a plant: five questions to think about if you want to keep your houseplants healthy

Chris Thorogood , University of Oxford

I’ve created a monstera! How to care for the ‘Swiss cheese plant’ in your life

Climate change threatens spring wildflowers by speeding up the time when trees leaf out above them

Richard B. Primack , Boston University ; Benjamin R. Lee , University of Pittsburgh , and Tara K. Miller , University of Virginia

Once the Callery pear tree was landscapers’ favorite – now states are banning this invasive species and urging homeowners to cut it down

Ryan W. McEwan , University of Dayton

Some houseplants take in nutrients from roots outside the soil – and it may change how we care for them

Amanda Rasmussen , University of Nottingham

A new discovery shows major flowering plants are 150 million years older than previously thought

Byron Lamont , Curtin University

I spent a year squeezing leaves to measure their water content. Here’s what I learned

Tomás I. Fuenzalida , Australian National University

Botanists are disappearing – just when the world needs them most

Sebastian Stroud , University of Leeds

How to grow plants on the moon – new study

Monica Grady , The Open University

Related Topics

• Climate change
• Horticulture
• Native plants
• Photosynthesis
• Plant science

Top contributors

Senior Research Associate, School of Ecosystem and Forest Sciences, The University of Melbourne

Vice President of Academic Affairs and Dean of the College, Grinnell College

Professeur, Biologie et Biochimie végétales, IUF, Université de Lorraine

Founder of Msit No’kmaq

PhD Candidate, Social Justice Education, Ontario Institute for Studies in Education, University of Toronto

Henslow Research Fellow, University of Cambridge

Chair of ARC Centre of Excellence for Quantum Biotechnology, The University of Queensland

Research Associate Professor in Evolutionary Biology, The University of Western Australia

Senior Research Professor, Curtin University

Professor of Planetary and Space Sciences, The Open University

Associate Professor in Ecology and Evolution, UNSW Sydney

Research botanist at the Botanic Gardens and State Herbarium of South Australia/Environment Institute, University of Adelaide

Author and Research Fellow, UNSW Sydney

Professor of Plant Science, Lancaster University

Senior Zoologist and Botanical Curator, Queensland Herbarium

• X (Twitter)
• Unfollow topic Follow topic

Global Plants

Jstor global plants, explore historic collections, partner resources.

Download Global Plants promotional media, articles, presentations, and more.

Get Connected

A globally connected community of botanists collaborating to advance taxonomy and science.

Champion Plant Preservation

Give an herbarium in a developing nation access to the world's largest digitized collection of plants.

Featured Herbarium Universidad De Guadalajara

Keep current with global plants.

300+ contributing partners and growing

MSU Libraries

Research guides.

• Need help? Ask a Librarian

Botanical and Plant Biology Research Guide: Article Research

Article research.

• Catalog and Book Search
• eTextbooks, OER and Other Digital Works
• MSU and Michigan Resources
• Websites of interest
• Michigan Botanist / Great Lakes Botanist
• Mich. Acad. of Science, Arts, and Letters
• Plants for Bees and Pollinators
• Image Repositories

Article Research at MSUL

Articles contain the most current information published in a field of study.

Most professors and researchers prefer articles that are "scholarly" in nature.  Characteristics of scholarly journals are that they have the following qualities:

• The articles contain original research (such as scientific experiments, surveys and research studies)
• A list of references or sources is provided at the end of each article
• An editorial board, composed of experts in the field, reviews articles to decide whether they should be accepted; this is also known as "refereed," "peer-reviewed," "professional," or "academic".
• Uses a specialized vocabulary for that field.
• Contain few if any advertisements. If included, they are highly specialized and specific to scholarly discipline (i.e. specific laboratory equipment, medical tools and drugs).
• If you are uncertain about the scholarly nature of a journal, you all look up the title or ISSN in the periodical database Ulrichs Periodical Directory (UlrichsWeb) .  This database will tell you about the journal including the nature, it's audience, and in which databases it is indexed and abstracted.

The Library Catalog contains the TITLES to all of the print and electronic format journals to which we have access .  The Catalog does not list the articles within the journals. The individual articles can be found in the many article databases to which we subscribe.

Citation searching:

If you have a citation to an article, the easiest way to locate the article is to look up the title of the journal in the catalog .  Identify whether we own the journal and the format, print or electronic.  If in electronic format, do we have that year/volume? If yes, you can click on the link provided to go directly to the online articles and find the one you need.  If it is not online, do we have it in print?  If so, identify the call number and go to the stacks to find the proper volume and issue.  If we do not own the journal or issue, you can request the article through Interlibrary Services .

Article databases - 2nd choices

• Tree Species Range Maps from "Atlas of United States Trees" Maps of the ranges of tree species in North America compiled by Elbert Little, of the U.S. Department of Agriculture, Forest Service, and others (see references below) were digitized for use in USGS' vegetation-climate modeling studies. These digital map files are available as maps in PDF format and also as shapefiles for download.

Plant Sciences Librarian

Herbaria Specimens

JSTOR Global Plants JSTOR Global Plants (formerly JSTOR Plant Science) offers access to botanical and other resources from around the world including: •The world’s largest database of plant type specimens representing the botanical diversity of the planet. More than 600,000 specimens are available today. When complete, there will be an estimated 2.2 million. •Over 175,000 scientific research articles and other content dating back hundreds of years from leading academic journals including Kew Bulletin, Mycologia, International Journal of Plant Sciences, Science, PNAS, and others. •Foundational reference works and books such as The Useful Plants of West Tropical Africa, Flowering Plants of South Africa, and illustrations from Curtis's Botanical Magazine. •A significant set of correspondence, including Kew’s Directors' Correspondence which included hand-written letters and memorandum from the senior staff of Kew from 1841 to 1928. •More than 20,000 paintings, photographs, drawings, and other images.

Print indexes

• Index to American botanical literature, 1886-1966. by Torrey Botanical Club. Call Number: Z5351 .T6 v.1-4 Publication Date: 1969 A reproduction of an index published serially since 1886 in the Bulletin of the Torrey Botanical Club.
• Plant science catalog; botany subject index by National Agricultural Library Call Number: Z5351 .U5 v.1-15 Publication Date: 1958 15 volumes. Title on spine: Botany subject index.
• Bibliography of agriculture. Section D, Plant science.
• Next: Catalog and Book Search >>
• Last Updated: May 29, 2024 2:57 PM
• URL: https://libguides.lib.msu.edu/botany

The father-and-son duo Leopold and Rudolf Blaschka crafted thousands of scientifically accurate models of plants and sea creatures as teaching aids. 

The Cactus Hunters: Desire and Extinction in the Illicit Succulent Trade

• Harold W. Keller

Plant collectors and enthusiasts are attracted to cacti and succulents in part because of their showy flowers in comparison to body size for many species. For example, the cactus genus Mammillaria, among others, is often found in cactus collections. Nevertheless, this human attraction for the collection and growing of cacti has led to an extensive illegal trade of cacti well documented in this book. Cacti over collecting coupled with the fact that 31%, or about1500 cacti species, are considered threatened, results in harvesting pressure that creates environmental concerns for the preservation of these plants. Margulies’s book raises awareness to the problem of cactus collection, trading, and selling both legally and illegally.

How to Cite

• Endnote/Zotero/Mendeley (RIS)

Copyright (c) 2024 Botanical Research Institute of Texas

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License .

Most read articles by the same author(s)

• Brian A. Perry, Harold W. Keller, Edward D. Forrester, Billy G. Stone, A new corticolous species of Mycena sect. Viscipelles (Basidiomycota: Agaricales) from the bark of a Living American elm tree in Texas, U.S.A. , Journal of the Botanical Research Institute of Texas: Vol. 14 No. 2 (2020): Journal of the Botanical Research Institute of Texas
• Harold W. Keller, Relf L. Price, Billy G. Stone, Edward D. Forrester, Arcyria versicolor of western mountains, U.S.A. (Myxomycetes: Trichiales: Trichiaceae): a morphological and taxonomic study with observations of nivicolous species , Journal of the Botanical Research Institute of Texas: Vol. 14 No. 2 (2020): Journal of the Botanical Research Institute of Texas
• Harold W. Keller, Vanessa M. Marshall, A new iridescent corticolous myxomycete species (Licea: Liceaceae: Liceales) and crystals on American elm tree bark in Texas, U.S.A. , Journal of the Botanical Research Institute of Texas: Vol. 13 No. 2 (2019): Journal of the Botanical Research Institute of Texas
• Harold W. Keller, Amanitas of North America , Journal of the Botanical Research Institute of Texas: Vol. 15 No. 1 (2021): Journal of the Botanical Research Institute of Texas
• Harold W. Keller, Appalachian Mushrooms , Journal of the Botanical Research Institute of Texas: Vol. 15 No. 1 (2021): Journal of the Botanical Research Institute of Texas
• Harold W. Keller, Hogs Are Up , Journal of the Botanical Research Institute of Texas: Vol. 15 No. 1 (2021): Journal of the Botanical Research Institute of Texas
• Harold W. Keller, Echinacea: Herbal Medicine with a Wild History , Journal of the Botanical Research Institute of Texas: Vol. 11 No. 2 (2017): Journal of the Botanical Research Institute of Texas
• Harold W. Keller, The Restless and Relentless Mind of Wes Jackson , Journal of the Botanical Research Institute of Texas: Vol. 15 No. 1 (2021): Journal of the Botanical Research Institute of Texas
• Harold W. Keller, Trees, Shrubs, and Woody Vines in Kansas, Revised and Expanded Edition , Journal of the Botanical Research Institute of Texas: Vol. 16 No. 1 (2022): Journal of the Botanical Research Institute of Texas
• Harold W. Keller, Wild DFW: Explore the Amazing Nature in and Around Dallas-Fort Worth , Journal of the Botanical Research Institute of Texas: Vol. 17 No. 2 (2023): Journal of the Botanical Research Institute of Texas

Subscription

Login to access subscriber-only resources.

• Français (Canada)
• Français (France)
• Español (España)

Journal of the Botanical Research Institute of Texas ISSN 1934-5259 (print) | ISSN 2644-1608 (online) Copyright 2024 Botanical Research Institute of Texas

Published by  BRIT Press Email: [email protected] Call: 1-817-332-4441 Social Media: Twitter @JofBRIT , Instagram @journalofbrit Address: BRIT Press, 1700 University Drive, Fort Worth, TX 76107-3400

• University of Michigan Library
• Research Guides
• Articles & Databases
• Getting Started
• Journals & Ebooks
• Web Resources
• Books & Microform
• Research Facilities

Library Contact

Accessing Databases

Sometimes you may have trouble accessing a database, whether on campus or off.  A link may direct you to a page asking for login information, or payment information.

The University Library has already paid for your access to many databases.  If you run into problems, the link may not be running through the proxy server.  Try putting the proxy prefix in front of your link - http://proxy.lib.umich.edu/login?url=

Articles can also be obtained through Interlibrary Loan (ILL) if the Library does not have a subscription to a specific journal.

Already Have a Citation?

Databases for botanical research - articles & species data.

• PLANT SPECIES....................

The following databases are divided by topic into Plant Species , General Species Data , Agriculture and Forestry , and General Science/Ecology .

• International Plant Names Index (IPNI) Database of the names and associated basic bibliographical details of all seed plants. Product of the Royal Botanic Gardens (Kew), the Harvard University Herbaria, and the Australian National Herbarium. IPNI is an amalgam of Index Kewensis, the Gray Card Index, and the Australian Plant Names Index.
• JSTOR Global Plants This link opens in a new window JSTOR Global Plants (formerly JSTOR Plant Science) is a community-contributed database where worldwide herbaria can share their plant type specimens, experts can determine and update naming structures, students can discover and learn about plants in context, and a record of plant life can be preserved for future generations.
• UM Herbarium Databases Databases of plant species created by the University of Michigan Herbarium researchers, including type collections of vascular plants, bryophytes, fungi, and algae.
• GENERAL SPECIES DATA....................
• Encyclopedia of Life (EOL) The Encyclopedia of Life is a collaborative effort among several internationally known natural history institutions, with the goal of providing detailed information about all 1.8 million species of organisms on Earth via a single, free web portal. Content is synthesized from published literature and verified by volunteer scientists. Most of the content is text, although multimedia and interactive content is available for some entries.
• AGRICULTURE AND FORESTRY....................
• AGRICOLA A bibliographic database of the agricultural literature, containing records of materials acquired by the National Agriculture Library (NAL) and cooperating institutions. Index to articles in agriculture, soil sciences, forestry, and related areas.
• Biological and Agricultural Index Plus Biological and Agricultural Index is a bibliographic database that cites articles from more than 300 periodicals. Periodical coverage includes a wide range of scientific journals, from popular to professional, that pertain to biology, agriculture, forestry and ecology. It indexes English-language periodicals published in the United States and elsewhere.
• GENERAL SCIENCE/ECOLOGY....................
• Web of Science Combines three citation indexes--Arts & Humanities, Science Expanded, and Social Sciences--which permit searching for articles that cite a known author or work, as well as searching by subject, author, journal, and author address. Covers 8,400+ journals.
• Biosis Previews Comprehensive index to life sciences research literature. Covers journals (5000+), reports, meetings (1500+), reviews, and books in all areas of biology. Weekly email alerts available.
• Annual Reviews Provides access to authoritative, analytic reviews of research in 29 focused disciplines within the Biological & Medical, Physical, and Social Sciences. Permits searching within these three broad categories or across all 29 titles.
• BioOne Abstracts and Indexes This BioOne bibliographic database is an indexed and fully-searchable collection of abstracts that link to the fulltext articles available from the BioOne organization. BioOne provides a unique aggregation of over 65 high-impact bioscience research journals from more than 50 publishers.
• Ecology Abstracts Covers relevant papers on evolutionary biology, economics, and systems analysis as they relate to ecosystems or the environment.

Related Guides

Other resource guides that may be helpful...

• Biology Resources for basic research in biology, including: molecular, developmental, and cell biology; ecology and evolutionary biology; botany; and zoology.
• Finding Species Information A guide for finding factual information about particular plant and animal species.
• Environment and Sustainability U-M Libraries supports research in natural resources and environmental science through a variety of materials, both print and electronic.

UM Quick Links

• University of Michigan
• Matthaei Botanical Gardens and Nichols Arboretum
• Shapiro Library

100+ Botany Research Topics [Updated 2024]

Botany, the scientific study of plants, holds the key to understanding the intricate and fascinating world of flora that surrounds us. As we delve into the realm of botany research, we uncover a vast array of botany research topics that not only contribute specifically to our scientific knowledge but also play an important role in addressing real-world challenges. 

In this blog, we will embark on a journey through the rich landscape of botany research, exploring various captivating topics that researchers are delving into.

How to Select Botany Research Topics?

Table of Contents

Selecting an appropriate and engaging botany research topic is a crucial step in the research process. Whether you are a student working on a thesis, a scientist planning a research project, or someone passionate about exploring the wonders of plant biology, the right choice of topic can significantly impact the success and enjoyment of your research. 

Here are some guidelines on how to select botany research topics:

• Identify Your Interests:
• Start by reflecting on your own personal interests within the field of botany. Consider the aspects of plant biology that fascinate you the most. 
• Whether it’s plant physiology, taxonomy, ecology, genetics, or any other subfield, choosing a topic aligned with your interests can make the research process more enjoyable.
• Review Literature:
• Conduct a thorough review and it will be of existing literature in botany. Explore recent research articles, journals, and books to identify gaps in knowledge, emerging trends, and areas where further investigation is needed. 
• This can help you find inspiration and identify potential research questions.
• Consider Relevance:
• Assess the relevance of your chosen topic to the current state of botany and its applications. Consider how your research could contribute to addressing real-world challenges, advancing scientific knowledge, or informing practical solutions. 
• Relevant research topics often garner more attention and support.
• Evaluate Feasibility:
• Evaluate all possible feasibility of your chosen topic in terms of available resources, time constraints, and research capabilities. 
• Consider the accessibility of study sites, the availability of equipment and materials, and the level of expertise required. A feasible research topic is one that aligns with your resources and constraints.
• Collaborate and Seek Guidance:
• Discuss your ideas with mentors, professors, or colleagues in the field. 
• Collaborative discussions can provide valuable insights, help refine your research questions, and guide you toward topics that align with current research priorities.
• Consider working with a professional academic editor to review your work after you’ve finished writing it.
• Explore Emerging Technologies:
• Consider incorporating emerging technologies and methodologies in your research. This not only adds a contemporary dimension to your study but also opens up new possibilities for exploration. 
• Technologies like CRISPR-Cas9, high-throughput sequencing, and remote sensing have revolutionized botany research.
• Think Interdisciplinary:
• Botany often intersects with various other disciplines, such as ecology, genetics, molecular biology, environmental science, and more. 
• Consider interdisciplinary approaches to your research, as this can lead to innovative and comprehensive insights.
• Address Global Challenges:
• Botany research can play a crucial role in addressing global challenges like climate change, food security, and biodiversity loss. 
• Choosing a topic that contributes to solving or mitigating these challenges adds societal relevance to your work.
• Explore Local Flora:
• If applicable, explore the flora of your local region. Investigating plant species native to your area can have practical implications for local conservation, biodiversity studies, and environmental management.
• Stay Inquisitive and Open-Minded:
• Keep an open mind and stay curious. Scientific research often involves unexpected discoveries, and being open to exploration can lead to novel and exciting findings. 
• Be willing to adapt your research questions based on your findings and new insights.

100+ Botany Research Topics For All Students

Plant physiology.

• The Role of Plant Hormones in Growth and Development
• Mechanisms of Photosynthesis: A Comprehensive Study
• Impact of Environmental Stress on Plant Physiology
• Water Use Efficiency in Plants: Regulation and Adaptation
• Nutrient Uptake and Transport in Plants
• Signaling Pathways in Plant Defense Mechanisms
• Regulation of Flowering Time in Plants
• Physiological Responses of Plants to Climate Change
• Role of Mycorrhizal Associations in Plant Nutrition
• Stress Tolerance Mechanisms in Halophytic Plants

Plant Taxonomy

• Phylogenetic Analysis of a Plant Family: Case Study
• Integrating Molecular Systematics in Plant Taxonomy
• Plant DNA Barcoding for Species Identification
• Revision of a Plant Genus: Taxonomic Challenges
• Cryptic Species in Plant Taxonomy: Detection and Implications
• Floristic Diversity in a Specific Geographic Region
• Evolutionary Trends in Angiosperms
• Ethnobotanical Contributions to Plant Taxonomy
• Application of GIS in Plant Taxonomy
• Conservation Status Assessment of Endangered Plant Species

Plant Ecology

• Ecosystem Services Provided by Plants
• Dynamics of Plant-Animal Interactions in a Habitat
• Impact of Invasive Plant Species on Native Flora
• Plant Community Composition Along Environmental Gradients
• Ecological Consequences of Plant-Pollinator Decline
• Microbial Interactions in the Rhizosphere
• Plant Responses to Fire: Adaptation and Recovery
• Climate Change Effects on Plant Phenology
• Restoration Ecology: Reintroducing Native Plants
• Plant-Soil Feedbacks and Ecosystem Stability

Plant Pathology

• Molecular Mechanisms of Plant-Pathogen Interactions
• Emerging Plant Diseases: Causes and Consequences
• Integrated Disease Management in Agriculture
• Fungal Pathogens: Diversity and Control Strategies
• Plant Immunity and Defense Mechanisms
• Resistance Breeding Against Viral Pathogens
• Bacterial Diseases in Crop Plants: Diagnosis and Management
• Impact of Climate Change on Plant Pathogen Dynamics
• Biocontrol Agents for Plant Disease Management
• Genetic Basis of Host Susceptibility to Plant Pathogens

Ethnobotany

• Traditional Medicinal Plants: Documentation and Validation
• Cultural Significance of Plants in Indigenous Communities
• Ethnobotanical Survey of a Specific Region
• Sustainable Harvesting Practices of Medicinal Plants
• Traditional Plant Use in Rituals and Ceremonies
• Plant-Based Foods in Indigenous Diets
• Ethnopharmacological Studies on Antimicrobial Plants
• Conservation of Ethnobotanical Knowledge
• Ethnobotanical Contributions to Modern Medicine
• Indigenous Perspectives on Plant Conservation

Genetic and Molecular Biology

• CRISPR-Cas9 Applications in Plant Genome Editing
• Epigenetics in Plant Development and Stress Response
• Functional Genomics of Plant Responses to Abiotic Stress
• Genetic Diversity in Crop Plants and its Conservation
• Genetic Mapping and Marker-Assisted Selection in Plant Breeding
• Genome Sequencing of Non-Model Plant Species
• RNA Interference in Plant Gene Regulation
• Comparative Genomics of Plant Evolution
• Genetic Basis of Plant Adaptation to Extreme Environments
• Plant Epigenome Editing: Methods and Applications

Plant Anatomy and Morphology

• Comparative Anatomy of C3 and C4 Plants
• Xylem and Phloem Development in Plants
• Leaf Anatomy and Adaptations to Photosynthesis
• Morphological Diversity in Plant Reproductive Structures
• Evolution of Floral Symmetry in Angiosperms
• Root Architecture and its Functional Significance
• Stem Cell Dynamics in Plant Meristems
• Comparative Morphology of Succulent Plants
• Tissue Regeneration in Plants: Mechanisms and Applications
• Wood Anatomy and Tree-Ring Analysis in Dendrochronology

Climate Change and Plant Responses

• Impact of Global Warming on Alpine Plant Communities
• Plant Responses to Elevated CO2 Levels
• Drought Tolerance Mechanisms in Plants
• Shifts in Plant Phenology Due to Climate Change
• Climate-Induced Changes in Plant-Pollinator Interactions
• Carbon Sequestration Potential of Forest Ecosystems
• Ocean Acidification Effects on Seagrass Physiology
• Plant Responses to Increased Frequency of Extreme Events
• Alpine Plant Adaptations to Harsh Environments
• Climate-Driven Changes in Plant Distribution and Biogeography

Emerging Technologies in Botany Research

• Application of Machine Learning in Plant Phenotyping
• Nanotechnology in Plant Science: Current Status and Future Prospects
• Metagenomics in Studying Plant Microbiomes
• Remote Sensing for Monitoring Plant Health
• High-Throughput Sequencing in Plant Genomics
• CRISPR-Based Gene Drives for Ecological Restoration
• Advances in Plant Imaging Techniques
• Synthetic Biology Approaches in Plant Engineering
• Augmented Reality Applications in Plant Biology Education
• Digital Herbariums: Integrating Technology in Plant Taxonomy

Misc Botany Research Topics

• Metabolic Pathways in Plant Secondary Metabolism: Regulation and Significance
• Population Genomics of Endangered Plant Species: Implications for Conservation
• Impact of Soil Microbes on Plant Health and Productivity
• Evolutionary Dynamics of Plant-Pathogen Coevolution: Insights from Molecular Data
• Application of CRISPR-Based Gene Editing for Improving Crop Traits
• Phytochemical Profiling of Medicinal Plants for Drug Discovery
• Investigating the Role of Epigenetic Modifications in Plant Stress Responses
• Role of Plant Volatile Organic Compounds (VOCs) in Ecological Interactions
• Biotic and Abiotic Factors Influencing Plant Microbiome Composition
• Molecular Basis of Plant-Microbe Symbiosis: Lessons from Nitrogen-Fixing Associations

How to Make Botany Research Successful?

Conducting successful botany research involves a combination of careful planning, effective execution, and thoughtful analysis. Whether you are a student, a researcher, or someone conducting independent studies, here are key tips to ensure the success of your botany research:

• Establish Clear Objectives: Clearly articulate the goals and objectives of your research. What specific inquiries do you intend to address? A well-defined research focus serves as a guiding framework, ensuring your efforts remain purposeful and on course.
• Conduct an In-Depth Literature Review: Immerse yourself in the existing body of literature within your field of study. Identify gaps, discern trends, and pinpoint areas where your research could contribute significantly. A thorough literature review lays a robust groundwork for shaping your research design.
• Choose an Appropriate Research Topic: Select a research topic that resonates with your interests, aligns with your expertise, and addresses the current needs of the scientific community. Ensure that the chosen topic is not only feasible but also harbors the potential for impactful outcomes.
• Develop a Sound Research Plan: Create a detailed research plan outlining the methodologies, timelines, and resources required. A well-structured plan helps in efficient execution and minimizes the risk of unforeseen challenges.
• Utilize Cutting-Edge Technologies:  Stay updated with the latest technologies and methodologies in botany research. Incorporate advanced tools such as high-throughput sequencing,  CRISPR-Cas9 , and remote sensing to enhance the precision and efficiency of your research.
• Collaborate and Seek Guidance: Collaborate with experts in the field, seek mentorship, and engage in discussions with colleagues. Networking and collaboration can provide valuable insights, guidance, and potential avenues for collaboration.
• Ensure Ethical Considerations: Adhere to ethical guidelines and standards in your research. Obtain necessary approvals for human subjects, follow ethical practices in plant experimentation, and ensure the responsible use of emerging technologies.
• Implement Robust Experimental Design: Design experiments with attention to detail, ensuring that they are replicable and provide statistically significant results. Address potential confounding variables and incorporate controls to enhance the reliability of your findings.
• Collect and Analyze Data Thoughtfully: Implement systematic data collection methods. Use appropriate statistical analyses to interpret your results and draw meaningful conclusions. Transparent and well-documented data analysis enhances the credibility of your research.
• Regularly Review and Adapt: Periodically review your progress and be open to adapting your research plan based on emerging findings. Flexibility and responsiveness to unexpected results contribute to a dynamic and successful research process.
• Communicate Your Research Effectively: Share your findings through publications, presentations, and other relevant channels. Effective communication of your research results contributes to the broader scientific community and enhances the impact of your work.
• Foster a Collaborative Research Environment: Encourage collaboration within your research team. A collaborative environment fosters creativity, diverse perspectives, and a collective effort towards achieving research goals.
• Contribute to Sustainable Practices: If your research involves fieldwork or plant collection, adhere to sustainable practices. Consider the impact on local ecosystems and strive to minimize any negative consequences.
• Stay Resilient: Research can have its challenges, setbacks, and unforeseen obstacles. Stay resilient, remain focused on your goals, and view challenges as opportunities for growth and learning.
• Celebrate Achievements and Learn from Failures: Acknowledge and celebrate your achievements, no matter how small. Learn from any setbacks or failures and use them as lessons to refine and improve your research approach.

In the vast and diverse field of botany research, scientists are continually unraveling the mysteries of the plant kingdom. From the intricate processes of photosynthesis to the challenges posed by emerging plant diseases and the potential of cutting-edge technologies, botany research is a dynamic and ever-evolving field. 

As we delve deeper into the green secrets of the plant world, our understanding grows, offering not only scientific insights but also solutions to address pressing global challenges such as food security, biodiversity loss, and climate change. 

The exploration of botany research topics is a journey of discovery, paving the way for a sustainable and harmonious coexistence with the plant life that sustains our planet.

Related Posts

Step by Step Guide on The Best Way to Finance Car

The Best Way on How to Get Fund For Business to Grow it Efficiently

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

• Advanced Search
• Journal List
• Front Pharmacol
• PMC10569491

Current state of research on the clinical benefits of herbal medicines for non-life-threatening ailments

Sandra salm.

1 Institute of Pharmaceutical Biology, Goethe University, Frankfurt, Germany

2 Institute of General Practice, Goethe University, Frankfurt, Germany

Jochen Rutz

3 Department of Urology and Pediatric Urology, University Medical Center Mainz, Mainz, Germany

Marjan van den Akker

4 Department of Family Medicine, Care and Public Health Research Institute, Maastricht University, Maastricht, Netherlands

5 Department of Public Health and Primary Care, Academic Centre of General Practice, KU Leuven, Leuven, Belgium

Roman A. Blaheta

Beatrice e. bachmeier.

Marilena Gilca , Carol Davila University of Medicine and Pharmacy, Romania

Associated Data

The original contributions presented in the study are included in the article/ Supplementary Material , further inquiries can be directed to the corresponding author.

Herbal medicines are becoming increasingly popular among patients because they are well tolerated and do not exert severe side effects. Nevertheless, they receive little consideration in therapeutic settings. The present article reviews the current state of research on the clinical benefits of herbal medicines on five indication groups, psychosomatic disorders, gynecological complaints, gastrointestinal disorders, urinary and upper respiratory tract infections. The study search was based on the database PubMed and concentrated on herbal medicines legally approved in Europe. After applying defined inclusion and exclusion criteria, 141 articles were selected: 59 for psychosomatic disorders (100% randomized controlled trials; RCTs), 20 for gynecological complaints (56% RCTs), 19 for gastrointestinal disorders (68% RCTs), 16 for urinary tract infections (UTI, 63% RCTs) and 24 for upper respiratory tract infections (URTI) (79% RCTs). For the majority of the studies, therapeutic benefits were evaluated by patient reported outcome measures (PROs). For psychosomatic disorders, gynecological complaints and URTI more than 80% of the study outcomes were positive, whereas the clinical benefit of herbal medicines for the treatment of UTI and gastrointestinal disorders was lower with 55%. The critical appraisal of the articles shows that there is a lack of high-quality studies and, with regard to gastrointestinal disorders, the clinical benefits of herbal medicines as a stand-alone form of therapy are unclear. According to the current state of knowledge, scientific evidence has still to be improved to allow integration of herbal medicines into guidelines and standard treatment regimens for the indications reviewed here. In addition to clinical data, real world data and outcome measures can add significant value to pave the way for herbal medicines into future therapeutic applications.

1 Introduction

Plant derived drugs have been used since humans have started treating physical and mental illnesses. They are part of Traditional Medicine in different cultures all over the world ( Yuan et al., 2016 ). Since then, medicine and treatment procedures have evolved and while in Traditional Medicine a holistic approach of life focusing on health and its maintenance was common philosophy, present Modern Medicine has a clear emphasis on unravelling the changes leading to disease and eradiating it ( Fries, 2019 ). Traditional medicine has a rigorous algorithm of identifying the root of the disease, which is based on traditional concepts, which, unfortunately, are considered obsolete nowadays, despite their practical longevity (e.g., acupuncture, ayurveda). The problem is that this traditional medical epistemology is not fully understood and science has limited tools to “translate” it into modern terms.

With the success of synthetic drugs along with the design of targeted therapies interfering specifically with the respective disease-related signaling pathways, herbal medicines have been eliminated from modern rational treatment strategies. The most important obstacles for the use in novel therapy strategies is that markers to measure clinical efficacy of herbal medicine have not been developed so far. Markers of efficacy of herbal drugs could also be useful to distinguish between patients who could benefit from a therapy with herbal medicines from those who will not. First preclinical studies already indicate that those markers or “signatures” (e.g., mRNA, miRNA) could be found in the future ( Bachmeier et al., 2007 ; Bachmeier et al., 2008 ; Bachmeier et al., 2009 ; Bachmeier et al., 2010 ; Killian et al., 2012 ; Kronski et al., 2014 ).

In the last years, more and more patients report on the perceived efficacy of herbal drugs and praise the absence of undesired side effects and the good tolerability.

The following section provides insights into the standard therapies of selected ailments for which herbal medicines may be a rational alternative.

1.1 Indications suitable for treatment with herbal medicines

Herbal medicines are in particular suitable for the treatment of non-life-threatening conditions for which knowledge from traditional use is available pointing to their clinical benefits in treating the respective ailment ( Wachtel-Galor and Benzie, 2011 ). This applies especially to psychosomatic disorders, gynecological complaints, and upper respiratory tract infections. However also for other diseases like gastrointestinal diseases, urinary tract infections herbal medicines have been clinically applied and—as we will show in this review—with some success.

Standard Care of psychosomatic disorders comprises the application of synthetic psychotropic drugs and psychotherapy ( Laux, 2021 ). Psychotropic drugs are used not only for the treatment of depressive disorders and anxiety, but also for sleep disorders, excitation and chronic pain ( Gründer and Benkert, 2012 ). However undesired adverse events having negative impact on quality of life can occur like, e.g., weight gain, sexual dysfunction, sedation, headache and tremor ( Grunze et al., 2017 ). In addition their use, in particular benzodiazepines, can lead to addiction and drug abuse ( Soyka and Mann, 2018 ) and interactions with other medication has to be taken into consideration especially in older multimorbid patients ( Burkhardt and Wehling, 2010 ). About 23% of all over 70-year-old people have psychosomatic disorders with about 40% requiring therapy ( Haupt and Vollmar, 2008 ). In this context herbal medicines represent an interesting alternative to avoid the above-mentioned problems with standard synthetic drugs. However, they do not belong to standard therapy-options and therefore are underrepresented in therapy-guidelines ( Bittel et al., 2022 ). Nevertheless they play an important role in self-medication of patients ( Stange, 2014 ) probably due to their favorable ratio between benefit and side-effects.

Gynecological complaints include, e.g., menopausal and premenstrual symptoms. According to the German medical guideline for post- and perimenopause, vasomotor symptoms of the peri- and post-menopause such as hot flushes and sweating should be treated with hormone therapy for menopause (hormone replacement therapy; HRT), if not contraindicated ( AWMF, 2020 ). The side effects of HRT include edema, joint pain, psychological symptoms or even thrombosis and breast cancer ( Maclennan et al., 2004 ). Herbal medicines, on the other hand, are characterized by a low risk of adverse events which increases patients’ adherence and in consequence prevents therapy discontinuations ( AWMF, 2020 ). Premenstrual syndrome (PMS) is characterized by recurring physical and psychological symptoms in the days before menstruation. There are currently no medical guidelines in German-speaking countries for the treatment of PMS. Systematic reviews on hormonal treatments (oral contraceptives, progesterone and estrogen) ( Ford et al., 2006 ; Lopez et al., 2007 ; Naheed et al., 2013 ; Kwan and Onwude, 2015 ) and acupuncture/acupressure ( Armour et al., 2018 ) point to ambiguous evidence. Treatment with serotonin reuptake inhibitors was shown to be effective but was associated with frequent side effects, e.g., nausea and asthenia ( Marjoribanks et al., 2013 ).

Gastrointestinal diseases include several conditions like irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), liver disease (hepatitis), and functional dyspepsia (FD).

Beside dietary changes, stress management and psychotherapy, severe cases of IBS and IBD require additional medication to reduce inflammation or to slow down the intestinal irritations. However patients often complain about the side effects of medical treatment like, e.g., dizziness or weight gain (particularly caused by steroids), or undesired fatigue, headache, and/or tiredness associated with the intake of methotrexate ( Feagan et al., 1995 ). Common types of hepatitis are viral hepatitis B and C. Antiviral therapy represents the treatment of choice to fight the virus caused disease. However, poor tolerability and significant adverse effects that include, for example, headaches, dizziness, depression, and irritability often lead to treatment discontinuation, further decreasing response rates ( Cornberg et al., 2002 ). FD is a common gastrointestinal disorder treated by proton pump inhibitors (PPI) or H2 receptor antagonist, and/or treatment with tricyclic antidepressants or prokinetic agents. As in all cases, adverse side effects may occur ranging from dizziness to the development of diabetes mellitus type 2 ( Yuan et al., 2021 ).

Urinary tract infections (UTI) with estimated 150 million cases worldwide each year reflect the most common outpatient infections ( Zavala-Cerna et al., 2020 ). Women are more susceptible than men with a lifetime incidence of 50%–60%. Application of antibiotics represents the standard treatment regimen to overcome the infection. However, serious side effects, predominantly exerted on the digestive system, may outweigh the benefits of this drug class. Most importantly, routine use of antibiotics bears the risk to trigger the selection of resistant strains. Hence, avoiding antibiotic treatment of UTI has gained high priority among the urologic community ( Jung et al., 2023 ). Lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) requires a medical therapy which aims to reduce the BPH-related complications. A range of synthetic drugs is available to treat this condition. However, these have a range of side effects, including postural hypotension, dizziness, asthenia, abnormal ejaculation, intraoperative floppy iris syndrome (α1-blocker), or decreased libido, gynecomastia, and erectile dysfunction (5α-reductase inhibitors) ( Cheng et al., 2020 ). Due to this, patients often discontinue treatment.

The most common acute upper respiratory infections include bronchitis, rhinosinusitis and common cold. Common cold or acute viral rhinosinusitis is triggered by a viral infection/inflammation of the nose and by definition has a duration up to 10 days. According to Jaume and co-workers ( Jaume et al., 2020 ) the recommended therapy (mainly symptomatic) contains of paracetamol, NSAIDs, second-generation antihistamines to reduce symptoms the first 2 days; nasal decongestants with small effect in nasal congestion in adults; combination of analgesics and nasal decongestants; ipratropium bromide for reducing rhinorrhea; probiotics; zinc when administered the first 24 h after the onset of symptoms; nasal saline irrigations; and some herbal medicines. About 5% of adults have an episode of acute bronchitis each year. An estimated 90% of these seek medical advice for the same ( Saust et al., 2018 ). Acute bronchitis is caused by infection of the large airways commonly due to viruses and is usually self-limiting. Bacterial infection is uncommon. Still, often antibiotics are prescribed, despite lacking effectiveness ( Tanner and Karen Roddis, 2018 ). Most medical guidelines advice a “wait-and-see” policy, the use of antihistamines and cough medicines is discouraged.

1.2 Objectives

In the last decade we experienced a renaissance of herbal medicines with a rising demand especially for the treatment of the before-mentioned indications. This implicates that there is an urgent need for a scientific progress towards a rational phytotherapy, which will combine the benefits of “Modern Medicine” with the “Traditional Knowledge” on the therapeutic benefits of herbal medicines.

In order to create a basis of knowledge to build upon novel interdisciplinary research ideas towards the establishment of herbal medicines into rational therapeutic strategies, we extracted information from clinical studies. Thereby we aimed to get an overview on.

• - which herbal medicines have been studied so far for which ailment
• - which outcomes have been studied
• - what quality level (level of evidence) the published studies have

Answering these questions, we create a comprehensive critical picture of the current knowledge on clinical efficacy and benefits as well as on failures and possible adverse events. Based on the results of these studies we give recommendations for practitioners and patients.

2.1 Search strategy and selection of scientific reports

Information on the therapeutic use of herbal medicines in different ailments was collected from scientifically published articles by conducting a search in the database PubMed for each of the five indication groups according to the following inclusion and exclusion criteria.

2.1.1 Inclusion criteria

• 1. Herbal Medicine
• a.Psychosomatic symptoms (depressive disorder, sleeping disorders/insomnia, anxiety, cognitive impairment)
• b.Gynecological complaints (climactic symptoms, menstrual symptoms, premenstrual syndrome)
• c.Gastrointestinal disorders/dyspepsia
• d.Urinary tract infections
• e.Upper respiratory tract infections
• 3. Clinical Trial
• Exclusion criteria
• a. Reports in languages other than German or English language
• b. No full-text available
• c. Study protocols
• d. Traditional medicine (e.g., Traditional Chinese Medicine, Ayurveda, etc. ),
• e. Aroma therapy
• f. Dietary supplements
• g. Self-made extracts and preparations
• h. Adjuvant treatment with herbal medicine
• i. Herbal medicines without market access in the EU
• j. In vivo / in vitro studies (pre-clinical studies)
• k. Homeopathy
• l. Acupuncture/acupressure
• m. Children and youth (under the age of 18 years)
• n. Healthy volunteers
• o. Primary preventive interventions (incl. Pre-post-operative complaints)
• p. Predominant comorbidities
• q. Case studies/case reports
• r. Televised, internet-based or web-based trials

Reasons for exclusion criteria:

a, b: Authors should be able to read and understand the full text; c: clinical results should have been obtained from a study; d, e, f, g, h, i: selected in order to filter all available information on legally approved (in Europe in particular in Germany) herbal medicines or the respective standardized extract (HMPC Monographs of the European Medical Agency - EMA) only; j: preclinical evidence should be excluded; k, l: alternative naturopathic therapy forms should be excluded; m: children should be excluded due to different drug metabolism; n, o: healthy volunteers should be excluded in order to obtain information on clinical therapeutic benefits; p: predominant comorbidities should be excluded because they can affect the efficacy of the herbal drug in particular when co-administered with other drugs; q; clinical benefits from single cases are difficult to generalize; r: excluded for methodological reasons, e.g., data interpretation.

2.2 Data extraction and quality assessment of scientific reports

To get an overview on the characteristics of all included articles, a table was created for each indication group containing information on the publication, the study design, the population and treatment duration, the indication and the primary outcome, the herbal medicine and comparison treatment (comparator) as well as the results. Furthermore, we performed a quality assessment of the collected reports according to the following scoring method.

• • 1 point for an observational study or a pre-post observational comparison
• • 2 points for a clinical trial
• • 3 points for a randomized controlled trial plus 1 additional point for blinding

Thereby, a score between 1 and 4 was obtained indicating the quality for all scientific reports; respectively publications with the highest level of evidence (RCT + blinded) had a scoring value of four points (see Figures 1 – 5 ).

Numbers of studies and outcomes.

3.1 Psychosomatic disorders

A search for publications with the terms “psychosomatic disorder” and “herbal medicine” yielded only 64 results. Therefore, the search was extended with more specific terms (see inclusion criteria) yielding in 4.440 hits for depressive disorder, 1.907 hits for sleeping disorders, 2.380 hits for anxiety and 1.374 hits for cognitive impairment including Alzheimer’s disease. After eliminating all publications according to the exclusion criteria 59 publications remained. Among those, 39 studies were related to depressive disorders, 4 to sleeping disorders, 6 to anxiety and 10 to cognitive impairment and Alzheimer’s disease (neurological disorders). Most of them were double blind randomized controlled trials (quality group 4). For the treatment of depressive disorders predominantly Hypericum perforatum L (St. John’s Wort; SJW) was used and only few studies examined the clinical benefits of Rhodiola rosea L (Rosewood). Valeriana officinalis L (Valerian Root) and Humulus lupulus L (Hops) extracts were preferred for the treatment of sleeping disorders, while for anxietyextracts of Lavandula angustifolia (Lavender) were studied. Extracts of Ginkgo biloba L (Maidenhair Tree) were used in clinical studies with patients having neurological disorders (cognitive impairment and Alzheimer’s disease). Supplementary Table S1 provides an overview of the studies, their characteristics and results (see also Figure 1 ).

3.1.1 Depressive disorders

The use of herbal medicines in depressive disorders is well examined and in particular the clinical benefits of SJW are well supported by clinical studies of high quality. All 37 selected studies on the use of SJW in depressive disorders ranging from mild to severe forms have been double-blind randomized controlled trials (quality group 4). Study duration was predominantly between 4 and 8 weeks and only few studies examined the effects for longer time periods of up to 6 months. The majority of the studies reported positive therapeutic effects concerning Hamilton depression rating scale (HAMD) as primary outcome parameter and only 5 of them ( Shelton et al., 2001 ; Davidson et al., 2002 ; Bjerkenstedt et al., 2005 ; Moreno et al., 2006 ; Rapaport et al., 2011 ) did not demonstrate superiority as compared to placebo or pre-post.

In six studies (published predominantly before the year 2000) comparing SJW with tricyclic anti-depressive drugs the clinical benefits of the herbal drug in respect to placebo or in pre-post comparison was at least equal to the synthetic drug no matter if it was imipramine ( Vorbach et al., 1994 ; Vorbach et al., 1997 ; Philipp et al., 1999 ; Woelk, 2000 ), maprotiline ( Harrer et al., 1994 ) or amitriptyline ( Wheatley, 1997 ). However, with regards to tolerability, SJW was clearly superior to any of the tricyclic antidepressants.

The more recent studies compared the efficacy of SJW with the selective serotonin reuptake inhibitors (SSRI) paroxetine, sertraline, citalopram and fluoxetine. In most of the 18 studies the therapeutic benefits of SJW were at least equal to those of the SSRIs ( Harrer et al., 1999 ; Berger et al., 2000 ; Brenner et al., 2000 ; Friede et al., 2001 ; van Gurp et al., 2002 ; Bjerkenstedt et al., 2005 ; Gastpar et al., 2005 ; Szegedi et al., 2005 ; Anghelescu et al., 2006 ; Gastpar et al., 2006 ; Sarris et al., 2012 ). In two studies SJW was even superior to fluoxetine ( Fava et al., 2005 ) or paroxetine ( Seifritz et al., 2016 ) in reducing depressive symptoms. In one study the responders of a previous study were included in a further RCT testing the efficacy of SJW against citalopram. Here the numbers of patients with relapse was lower in the SJW group as compared to citalopram ( Singer et al., 2011 ). The results of one study indicated that SJW was less efficacious than both fluoxetine and placebo, however in this study the group on SJW had the lowest remission rates ( Moreno et al., 2006 ). In two studies no statistical differences in HAMD scores between SJW, placebo and citalopram ( Rapaport et al., 2011 ) or sertraline ( Davidson et al., 2002 ) could be found with adverse effects in the SJW and the SSRI groups.

In most of the above-mentioned studies, comparing the efficacy of SJW to standard therapy, a placebo group was included. However, in 13 studies SJW was tested exclusively against placebo whereby two of these studies examined the efficacy of different dosages of SJW extract ( Laakmann et al., 1998 ; Kasper et al., 2006 ). In these studies, the higher concentrations had the better clinical benefits. In a continuation study of the effect of SJW in long term treatment a higher dosage (1,200 mg/d) was not superior to the lower one (600 mg/d) ( Kasper et al., 2007 ). Interestingly the higher dosages were still well tolerated although mild adverse events related to gastrointestinal disorders were observed in a small portion of the patients ( Kasper et al., 2006 ). In only one of our selected studies SJW was not effective in comparison to placebo for the treatment of major depression but safe and well tolerated ( Shelton et al., 2001 ). In all other studies SJW was superior to placebo no matter if given in low ( Laakmann et al., 1998 ; Lecrubier et al., 2002 ; Randlov et al., 2006 ), medium ( Kasper et al., 2006 ; Kasper et al., 2007 ; Mannel et al., 2010 ) or in high ( Hansgen et al., 1994 ; Harrer et al., 1994 ; Sommer and Harrer, 1994 ; Kalb et al., 2001 ; Uebelhack et al., 2004 ; Kasper et al., 2006 ; Kasper et al., 2007 ; Kasper et al., 2008 ) dosages.

For the efficacy of Rhodiola rosea in treatment of depressive disorders only few studies were performed so far. Therefore, a clear conclusion cannot be drawn, especially as the outcomes are not homogenous. While one study investigating the efficacy of R. rosea against placebo and the SSRI sertraline reported on a statistically not-significant inferiority of the herbal medicine ( Mao et al., 2015 ) another study demonstrated clinical benefits concerning the symptoms of depression, insomnia, emotional instability and somatization against placebo. In this study two dosages of R. rosea were tested and the higher dose (680 mg/d) showed even positive effects on self-esteem ( Darbinyan et al., 2007 ).

3.1.2 Sleeping disorder

Interestingly the search for qualitatively high clinical studies (according to our inclusion and exclusion criteria) revealed only few studies. The majority of them investigated the efficacy of valerian alone ( Donath et al., 2000 ) or in combination with hops ( Koetter et al., 2007 ) compared to placebo ( Donath et al., 2000 ; Koetter et al., 2007 ) or to oxazepam ( Dorn, 2000 ; Ziegler et al., 2002 ). All studies reported clinical benefits, however while the one research group reported that valerian alone was efficacious against insomnia ( Donath et al., 2000 ) the other group reported on clinical benefits only in combination with hops ( Koetter et al., 2007 ). Both study designs were placebo-controlled. In comparison to oxazepam valerian was not inferior and both therapy options improved sleep quality (SF-B) in a similar fashion ( Dorn, 2000 ; Ziegler et al., 2002 ).

3.1.3 Anxiety

Herbal Medicines with lavender extracts were clinically studied for the treatment of anxiety. Between 2010 and 2019 six qualitatively high studies performed in Germany, Austria and Switzerland reported on the beneficial effects of lavender against symptoms of anxiety with improvements on the Hamilton anxiety rating (HAMA) scale as primary outcome ( Kasper et al., 2010 ; Woelk and Schlafke, 2010 ; Kasper et al., 2014 ; Kasper et al., 2015 ; Kasper et al., 2016 ; Seifritz et al., 2019 ) and all studies used the same extract (WS1265). Four of the 6 studies were performed by the same group, however the study design differed. In these studies the efficacy of lavender was either compared to placebo ( Anghelescu et al., 2006 ; Kasper et al., 2010 ; Kasper et al., 2016 ; Seifritz et al., 2016 ) and/or to paroxetine ( Kasper et al., 2014 ) and lorazepam ( Woelk and Schlafke, 2010 ). Overall, the lavender preparation was regarded as efficacious and safe.

3.1.4 Neurological disorders (cognitive impairment and Alzheimer)

We selected 10 studies investigating the efficacy of ginkgo biloba extract in the treatment of cognitive impairment and Alzheimer’s Disease (AD) with 8 of them testing against placebo ( Le Bars et al., 1997 ; Le Bars et al., 2002 ; Le Bars, 2003 ; van Dongen et al., 2003 ; Schneider et al., 2005 ; Napryeyenko et al., 2007 ; Gavrilova et al., 2014 ; Gschwind et al., 2017 ), one against rivastigmine ( Nasab et al., 2012 ) and one against donepezil ( Mazza et al., 2006 ). In three of the studies two different ginkgo extracts did not show superiority over placebo regarding the primary outcome. In detail 5 of the studies showed that extracts of ginkgo biloba lead to a decrease in NPI composite score ( Gavrilova et al., 2014 ) improved significantly ADAS-Gog and GERRI ( Le Bars et al., 1997 ; Le Bars et al., 2002 ; Le Bars, 2003 ), or the SKT test battery ( Napryeyenko et al., 2007 ) as outcome parameters. In three studies ginkgo extracts did not show superiority over placebo regarding the primary outcome parameters ADAS-cog ( Schneider et al., 2005 ), gait analyses ( Gschwind et al., 2017 ) or SKT test-battery ( van Dongen et al., 2003 ), whereby in one of these studies the primary outcome parameter ADAS-cog also declined in the placebo group rendering the results of the study inconclusive ( Schneider et al., 2005 ). With respect to the AD conventional medication rivastigmine, ginkgo biloba extract was inferior regarding the primary outcome parameters MMSE and SKT test-battery ( Nasab et al., 2012 ). Finally one study in which gingko biloba was more efficacious than placebo and equal to the second generation cholinesterase inhibitor donepezil ( Mazza et al., 2006 ) was heavily criticized by two other groups ( Corrao et al., 2007 ; Korczyn, 2007 ), making it difficult to estimate if the use of ginkgo containing herbal medicines are justified for the treatment of mild to moderate AD.

3.2 Gynecological complaints

Of 383 search hits, 20 articles met the inclusion criteria. Eleven studies were related to menopausal symptoms and nine to PMS. Most were double-blind randomized controlled trials or observational studies ( Figure 2 ). The studies on menopausal symptoms reported mainly positive results and the results concerning PMS were exclusively positive ( Figure 2 ). The tested phytopharmaceuticals contained Cimicifuga racemosa (L.) (Black cohosh) (10 studies) and Salvia officinalis (Sage) (1 study) for the treatment of menopausal symptoms and Vitex agnus-castus L (VAC, Chaste tree) (8 studies) and SJW (1 study) for PMS. Supplementary Table S2 provides an overview of the study characteristics and results.

3.2.1 Menopausal symptoms

In studies examining the clinical benefits of black cohosh for the treatment of menopausal symptoms, sample sizes ranged from n = 62 to n = 6,141. Treatment duration was between 12 weeks and 9 months. The herbal drug dosages ranged from 20 to 127.3 mg.

In comparison to HRT, the benefit-risk-balance points to significant non-inferiority and superiority of black cohosh ( Bai et al., 2007 ). In three other studies menopausal complaints improved overall, but differences between black cohosh and HRT were not significant ( Wuttke et al., 2003 ; Nappi et al., 2005 ; Friederichsen et al., 2020 ). The combination of black cohosh with SJW significantly reduced menopausal complaints and was superior to transdermal estradiol ( Briese et al., 2007 ). Independent of a high or low dose, menopausal complaints decreased significantly ( Liske et al., 2002 ; Drewe et al., 2013 ). Adverse events rates were lower in the low dose group ( Drewe et al., 2013 ) or similar to the high dose group ( Liske et al., 2002 ). Menopausal symptoms decreased significantly more for black cohosh compared to placebo ( Osmers et al., 2005 ). In another study with 62 participants, the difference between the symptom scores just approached significance ( Wuttke et al., 2003 ). Interestingly, this also applies to the comparison of conjugated estrogens and placebo. Adverse events rates did not differ significantly between black cohosh and placebo ( Wuttke et al., 2003 ; Osmers et al., 2005 ). Significant and clinically relevant reductions in menopausal symptoms ( Vermes et al., 2005 ) or higher quality of life ( Julia Molla et al., 2009 ) were observed after treatment with black cohosh compared to therapy start. Sage taken for 8 weeks significantly decreased the number of menopausal hot flushes from week to week ( Bommer et al., 2011 ). Observed treatment-related adverse events were mild and occurred in only one person. However, no comparison was made to another treatment or placebo.

3.2.2 Premenstrual syndrome

Eight studies dealt with the treatment of PMS with VAC. The sample sizes ranged from n = 43 to n = 1,634. Treatment duration was three cycles; Berger et al. (2000) added three subsequent cycles without treatment. The administered dosages ranged from 1.6 to 20 mg extract.

Results of studies comparing VAC with pyridoxine or placebo were similar. PMS symptom reduction was significantly more pronounced for VAC compared to pyridoxine ( Lauritzen et al., 1997 ) or placebo ( Schellenberg, 2001 ; Bachert et al., 2009 ; Barrett et al., 2010 ; Schellenberg et al., 2012 ). Rates of adverse events were similar between groups in each study ( Loch et al., 2000 ; Schellenberg, 2001 ; Barrett et al., 2010 ; Schellenberg et al., 2012 ). Schellenberg et al. (2012) compared a VAC reference dose to a lower and higher dose; the results were in favor for the reference dose compared to the low dose. No significant differences between the high and reference dose emerged. The number of participants with adverse events was slightly elevated for the high dose. In single-arm studies, symptoms of PMS significantly decreased after three cycles of VAC treatment ( Berger et al., 2000 ; Loch et al., 2000 ; Momoeda et al., 2014 ). Only mild PMS-like adverse events were observed. Berger et al. demonstrated a gradual symptom return after therapy completion ( Berger et al., 2000 ). PMS symptoms were significantly higher compared to the end of the treatment, but still 20% lower than at baseline.

A clinical study testing the efficacy of SJW in treating mild PMS ( Canning et al., 2010 ) demonstrated significant improvements in physical (e.g., food craving) and behavioral (e.g., confusion) symptoms compared to placebo. The effect on mood (e.g., irritability) and pain (e.g., cramps) was not significant.

3.3 Gastrointestinal disorders

A search for publications with the search terms “gastrointestinal disorder” and “herbal medicine” yielded a total of 19 results after applying the exclusion criteria. Of these, eight studies were related to hepatic disorders, three publications dealt with IBD, two studies focused on IBS, and six studies had been done on FD. Most of them were done in a double-blinded randomized controlled manner ( n = 12) ( Figure 3 ). Silybum marianum (L.) Gaertn (Silymarin, milk thistle) was used in patients suffering from a hepatic disease. Patients with IBD were treated with Artemisia absinthium L (wormwood) or Potentilla erecta (tormentil). The standardized extract STW 5 containing Iberis amara (bitter candytuft), Glycyrrhiza glabra L (Liquorice), Carum carvi L (caraway), Mentha × piperita (peppermint), Melissa officinalis L (lemon balm) , Matricaria chamomilla (chamomile) , Angelica archangelica (wild celery), Chelidonium majus (greater celandine) and milk thistle has been applied in IBS and FD. The same has been done with the standardized extract STW 5-II which in contrast to STW 5 is free of wild celery, greater celandine, and milk thistle. SJW has been used to treat patients suffering from IBS. A combination of the standardized extracts WS 1340 (peppermint oil) and WS 1520 (caraway oil) was used for patients with FD. Supplementary Table S3 and Figure 3 provide an overview of the study characteristics and results.

3.3.1 Hepatic disease

Trials on steatohepatitis, cirrhosis and different kinds of hepatitis ( n = 18) included patient cohorts ranging from 14 to 200 participants, all of them aged >18 years. Patients were treated with silymarin orally or intravenously ( Pares et al., 1998 ; Tanamly et al., 2004 ; Ferenci et al., 2008 ; Hawke et al., 2010 ; Fried et al., 2012 ; Adeyemo et al., 2013 ; Fathalah et al., 2017 ; Tanwar et al., 2017 ) with dosages ranging from 280 to 2,100 mg/day or 5–20 mg/kg/day, respectively. Six studies compared the HM group to a placebo group ( Pares et al., 1998 ; Tanamly et al., 2004 ; Hawke et al., 2010 ; Fried et al., 2012 ; Adeyemo et al., 2013 ; Tanwar et al., 2017 ). Silymarin did not reduce virus titers and/or serum alanine transaminase (ALT) in patients with Hepatitis C and non-alcoholic Steatohepatitis C, compared to placebo ( Adeyemo et al., 2013 ). The same observation has been made by others ( Hawke et al., 2010 ). Furthermore, the integration of silymarin into a PEGylated (Peg)-interferon based regimen did not improve the outcome of HCV patients in terms of HCV RNA suppression and Enhanced Liver Fibrosis score performance ( Tanamly et al., 2004 ). There was also no effect of silymarin on HCV patients who were previously unsuccessfully treated with interferon (multicenter, double-blind, placebo-controlled trial) ( Fried et al., 2012 ). Although HCV-patients reported to “feel better” after 12 months of silymarin therapy in a further study, symptoms and quality of life (QOL) scores did not differ between the silymarin and the placebo group ( Tanamly et al., 2004 ). Treatment with silymarin was also well tolerated over a period of 2 years. However, the course of liver cirrhosis in this patient cohort has not been improved ( Pares et al., 1998 ). Contrasting these results, dose escalating studies on HCV cirrhotic patients revealed positive effects of silymarin or silibinin (also milk thistle), in a way that high-dosed silymarin (1,050 mg/day) improved QOL and biochemical parameters of chronic HCV-decompensated cirrhotic patients with no serious adverse events ( Ferenci et al., 2008 ; Fathalah et al., 2017 ) compared to low-dosed silymarin (420 mg/day). Notably, silibinin exerted a dose-dependent antiviral effect on Peg-interferon/ribavirin non-responders ( Ferenci et al., 2008 ; Fathalah et al., 2017 ).

3.3.2 Inflammatory bowel disease (IBD)

Between 2007 and 2009, three clinical trials on CD or IBD have been conducted, two in Germany (quality groups 1 and 2) and one in the United States (quality group 4) ( Huber et al., 2007 ; Omer et al., 2007 ; Krebs et al., 2010 ). Patients were treated with wormwood or tormentil for 3–10 weeks. A total of 30 patients were treated with wormwood or placebo ( Omer et al., 2007 ; Krebs et al., 2010 ). In this context, wormwood decreased tumor necrosis factor alpha levels and the CD activity index score, whilst scores for IBD questionnaire and Hamilton depression scale have been improved, compared to the controls ( Omer et al., 2007 ; Krebs et al., 2010 ). Daily intake of tormentil reduced clinical activity index scores in all patients, however, during the wash out phase scores increased again. Tormentil has been proven to be safe for ulcerative colitis patients in dosages up to 3,000 mg/day ( Huber et al., 2007 ).

3.3.3 Irritable bowel syndrome (IBS)

Symptoms of IBS were treated with STW 5 and STW 5-II or SJW (both studies were quality group 4) ( Madisch et al., 2004b ; Saito et al., 2010 ). The clinical trial carried out by Madisch et al. compared the effects of the treatment group with those of bitter candytuft mono-extract and placebo. STW 5 and STW 5-II (60 drops/day over 4 weeks) significantly reduced the total abdominal pain and the IBS score compared to placebo and bitter candytuft mono-extract ( Madisch et al., 2004b ). The study carried out by Saito and others investigated the clinical efficacy of SJW pointing to a lower effect as compared to placebo ( Saito et al., 2010 ).

3.3.4 Functional dyspepsia (FD)

Six studies on patients suffering from FD were performed, including treatment with either a WS 1520/WS 1340 combination ( n = 3) ( Madisch et al., 1999 ; Rich et al., 2017 ; Storr and Stracke, 2022 ) or with STW 5 ( von Arnim et al., 2007 ) and/or STW 5-II ( n = 3) ( Rösch et al., 2002 ; Madisch et al., 2004a ). WS 1340/WS 1520 was documented to be a “valuable” ( Storr and Stracke, 2022 ) or an “effective” therapeutic regimen ( Rich et al., 2017 ), as it relieved pain and improved disease-specific QOL, compared to placebo. The primary outcome of WS 1340/WS 1520 was also proven to be comparable to the prokinetic agent cisapride ( Madisch et al., 1999 ).

It is to be noted that the use of cisapride has meanwhile be restricted by the EMA due to the risk of potentially life-threatening cardiac arrhythmia [ https://www.ema.europa.eu/en/medicines/human/referrals/cisapride ].

Similar results have been presented in the STW 5 and STW 5-II trials. The gastrointestinal symptom score was significantly lowered when compared to the placebo group ( Madisch et al., 2004a ; von Arnim et al., 2007 ), with a therapeutic response comparable to cisapride ( Rösch et al., 2002 ).

3.4 Urinary tract infection (UTI) and lower urinary tract symptoms (LUTS)

Initial search on herbal drugs in urologic clinical trials pointed to 263 manuscripts published between 1983 and 2022. Narrowing the search to “herbal medicine” (HM) 18 relevant publications were identified. One publication was nearly identical to another one and, therefore, has not been taken care of in this chapter, one article only reviewed former trials (16 publications remaining). All of them were related to lower urinary tract infection (UTI), or acute uncomplicated cystitis, respectively. Four different HM have been applied, either compared to placebo or guideline-based treatment ( n = 12).

3.4.1 Urinary tract infections (UTI)

Several studies investigated the standardized herbal extract BNO 1045 which contains Centaurium erythraea Rafin, herba (Centaury); Levisticum officinale Koch, radix (Lovage); and Rosmarinus officinalis L., folium (Rosemary). In two studies, the clinical benefits of BNO 1045 in preventing UTI in high-risk women undergoing urodynamic studies (UDS) ( Miotla et al., 2018 ) or urogynecological surgeries ( Wawrysiuk et al., 2022 ) was evaluated. High-risk women were defined as: age over 70, elevated postvoid residual urine>100 mL, recurrent UTI, pelvic organ prolapse (POP) ≥II in POP-Q scale, and neurogenic bladder. No statistical differences in UTI incidence were found between patients receiving antibiotics or BNO 1045. No superiority of antibiotics over BNO 1045 has been confirmed as well in a subsequent prospective study on postoperative UTI after midurethral sling surgery (MUS) ( Rechberger et al., 2020 ). In another study, an herbal mixture based on D-mannose, Arctostaphylos uva-ursi, Betula pendula, and Berberis aristata was compared to BNO 1045 in reducing symptoms of UTI after MUS ( Rechberger et al., 2022 ). The rationale was based on the EAU 2022 guidelines which recommended D-mannose as prophylaxis of UTI. In this context, BNO 1045 was proven to be similar effective, compared to the herbal mixture. The use of BNO 1045 has been documented here to be a potential and valuable alternative to antibiotics for UTI prevention. All four trials have been carried out in the same institution involving the same main investigators which were (partially) associated with the manufacturer of BNO 1045.

A randomized, double-blind, multicenter Phase III clinical trials compared the efficacy and of BNO 1045 to antibiotics concerning symptoms and recurrence rates in women with uncomplicated UTI. Based on the endpoints “UTI-recurrence” and “additional antibiotics use”, BNO 1045 was proven to be non-inferior to antibiotic treatment ( Wagenlehner et al., 2018 ). In a retrospective cohort study, data from outpatients in Germany with at least one diagnosis of acute cystitis or UTI and a prescription of either BNO 1045 or standard antibiotics were analyzed ( Holler et al., 2021 ). Compared to antibiotics, BNO 1045 was associated with significantly fewer recurrence rates of UTI and with reduced additional antibiotic prescription. BNO 1045 was propagated to be an effective and safe symptomatic treatment option for acute cystitis or UTI.

In an open-labeled, randomized, controlled trail the effect of BNO 1045 to prevent recurrences of cystitis in younger women was evaluated ( Sabadash and Shulyak, 2017 ). All patients received an antibacterial therapy, the test group was additionally treated with BNO 1045. The integration of BNO 1045 prevented bacteriuria and recurrent cystitis episodes more frequently (primary outcome), compared to the control group without BNO 1045. This may indicate superiority of the combination therapy. However, interpretation of the results of the study is limited due to the lack of blinding on both sides - patients and physicians. A further study without any involvement of the manufacturer (no conflicts of interest noted) included younger women with acute uncomplicated cystitis. All patients received the same therapy, the nonsteroidal anti-inflammatory drug ketoprofen in combination with BNO 1045 ( Kulchavenya, 2018 ). Quite interestingly, although the majority of the patients responded well to the therapy, the investigators also observed patients who only slightly responded, or did not respond to treatment at all. The authors concluded that uncomplicated cystitis might be cured by BNO 1045 instead of antibiotics which may be required only in minor cases. Still, the data seems to be over-interpreted, since patients were treated with both ketoprofen and BNO 1045 which does not allow to conclude to one drug alone.

Aside from BNO 1045, further herbal medicines have been investigated in clinical studies. Tablets with a standardized herbal extract containing Armoraciae rusticanae radix (Horseradish root) (80 mg) and Tropaeoli majoris herba (Nasturtium) (200 mg) have been applied to patients suffering from chronically recurrent UTI symptoms, with the result that recurrent UTI symptoms were less, compared to the placebo group ( Albrecht et al., 2007 ). However, a subsequent trial failed to demonstrate non-inferiority of this extract to antibiotics due to a poor recruitment rate ( Stange et al., 2017 ). Actually, no respective clinical trials with sufficient statistical power are underway.

3.4.2 Lower urinary tract symptoms LUTS

Clinical studies have also been conducted with an herbal medicine containing the standardized extracts WS 1473 Sabal serrulata Schult.f (Sabal fruit) (160 mg) and WS1031 Urtica dioica L (Urtica root) (120 mg). All studies were related to the treatment of lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH). The study protocols (placebo-controlled, double-blind, multicentric) were similar in all trials with the International Prostate Symptom Score (I-PSS), quality of life index, uroflow and sonographic parameters as the outcome measures for treatment efficacy. In one study ( Lopatkin et al., 2005 ) patients were randomized to either the herbal medicine (WS 1473 and WS1031) (treatment group) or placebo (control group) while in another study patients received either WS 1473 and 1031 or the α1-adrenoceptor antagonist tamsulosin ( Engelmann et al., 2011 ). A further study was based on the previous mentioned study ( Lopatkin et al., 2005 ), whereby all patients were offered participation in a further 48-week follow-up with WS 1473/1031 ( Lopatkin et al., 2007 ). Independent on the study design, it was concluded that WS 1473/1031 is superior to the placebo, and not inferior to tamsulosin in the treatment of LUTS. In a later re-evaluation of the data sets, WS 1473/1031 was shown to significantly improve nocturnal voiding frequency compared to placebo, with similar effects compared to tamsulosin or the 5α-reductase inhibitor finasteride ( Oelke et al., 2014 ). No further studies have been enrolled since then. However, a database search in 2022 including 3,000 private practices in Germany revealed a significant association between WS 1473/1031 prescription and reduced incidence of urinary incontinence and urinary retention compared to tamsulosin and tamsulosin/dutasteride (5α-reductase blocker), as well as reduced incidence of erectile dysfunction compared to dutasteride ( Madersbacher et al., 2023 ). In all four studies the manufacturer of the extract was involved.

One observational study was investigating the effectiveness of a standardized herbal extract containing a combination of Cucurbita pepo L (Marrow), Rhus aromatica bark (Fragrant sumac), and hops, in women with overactive bladder ( Gauruder-Burmester et al., 2019 ). Of the 113 patients included, nearly the half (61 patients) used concomitant medications (e.g., antihypertensive, levothyroxine, lipid/cholesterol lowering agents, low dose ASS, NSAIDS) within the frame of a routine clinical setting. Considering the noninterventional character of this study, the herbal combination was demonstrated to improve overactive bladder symptoms and quality of life. A controlled study has not yet been initiated.

3.5 Upper respiratory tract infections (URTI)

The search on herbal medicines for the indication Upper Respiratory Infections revealed 24 publications.

The most common indications studied for the effectiveness of herbal medications were sinusitis, viral acute Rhisosinusitis (ARS) and common cold (N = 13), bronchitis (N = 8), and less frequently on acute cough (N = 2) and Acute lower and upper tract respiratory infections (N = 1) and chronic rhinosinusitis (N = 1). Most of them (N = 18) were double-blind randomized placebo-controlled trials, there were also randomized controlled trials that compared herbal medication to other herbal medication (N = 2) or to antibiotics (N = 1). Other study designs involved prospective cohorts (N = 3) and one retrospective cohort.

3.5.1 Sinusitis/common cold and chronic rhinosinusitis

Studies on treatment of acute sinusitis and acute rhinosinusitis used a follow-up period between 7 and 14 days, with the (adapted) Sinusitis Severity Score (SSS) (N = 2), the Major Symptom Score (MSS) (N = 4), the Total Symptom Score (N = 1) and facial pain relief (N = 1) as primary endpoints. All studies reported significantly improvement of the intervention group over the placebo or control group.

The treatment of acute sinusitis and acute rhinosinusitis with Eps 7630 (standardized root extract of Pelargonium sidoides DC (Pelargonium) was studied in two double blind randomised placebo controlled trials ( Bachert et al., 2009 ; Dejaco et al., 2019 ) and in one prospective ( Perić et al., 2020 ), randomized, open-label, non-inferiority study comparing study medication to Amoxicillin All three studies reported a significant superiority resp. Non-inferiority for Eps 7630. The use of the standardized herbal extract BNO 1016 ( Primulae flos (Primrose), Gentiana lutea Ruiz and Pav. Ex G.Don (Yellow gentian), Rumicis herba (Sorrel), Sambuci flos (Elderflower) and verbenae herba (Vervain) was tested in two randomised placebo controlled trials ( Jund et al., 2015 ), one of which was blinded ( Jund et al., 2015 ). Both studies showed stronger impact on the symptom score for BNO 1016 compared to placebo. One more study tested BNO 1016 in a multicenter, prospective, open-label study comparing its effect to intranasal fluticasone furoate, with patients in both groups showing improvement ( Passali et al., 2015 ). ELOM-080 (standardized herbal drug preparation containing specially destilled oils from Eucalyptus (Eucalypt) and Citrus ×sinensis (Sweet orange) and Myrtus (Myrtle) and Citrus limon (L.) Osbeck (Lemon oil)) was evaluated once in a double blind randomised placebo controlled trial ( Federspil et al., 1997 ) and once in a prospective, non-interventional parallel-group trial where the control group received BNO 1016 ( Gottschlich et al., 2018 ). In both studies BNO 1016 showed superior results.

The use of extracts containing Echinacea for the treatment of common cold was positively tested in two studies, reporting on total number of facial tissues used in three to 7 days after intervention start ( Naser et al., 2005 ) and on the Total Daily Symptom Scores (TDSS) after 7 days ( Goel et al., 2004 ). No statistically significant differences were observed between treatment groups for the total symptom score (SS) after 14 days. In two other studies testing capsules/pills containing Echinacea angustifolia root and Echinacea purpurea root and E. purpurea herb there was no statistically significant difference between the intervention and placebo group concerning severity and duration of self-reported symptoms ( Barrett et al., 2002 ) or global severity ( Barrett et al., 2010 ).

In a double blind randomised placebo controlled trial BNO 1016 was tested for the treatment of chronic rhinosinusitis. The results reveal that the herbal drug was not superior over placebo regarding the Major Symptom Score (MSS) in week 8 and week 12 ( Palm et al., 2017 ).

3.5.2 Bronchitis

For bronchitis, nine studies were included, of which six were double-blind randomized placebo-controlled trials, testing EPs 7630 (N = 5) ( Matthys et al., 2003 ; Chuchalin et al., 2005 ; Matthys and Heger, 2007 ; Matthys et al., 2010 ; Kähler et al., 2019 ) or ELOM-080 (N = 1) ( Gillissen et al., 2013 ). The prospective observational studies included a standardized syrup of Hedera helix L (Ivy leaves) (N = 1) ( Fazio et al., 2009 ), pills with ethanolic Ivy-leaves dry extracts (N = 1) ( Hecker et al., 2002 ) and EPs 7630 (N = 1) ( Matthys and Heger, 2007 ).

Using a follow-up period of 7 days to 4 weeks, all but one (double-blinded placebo controlled trial) ( Matthys et al., 2003 ) reported positive effects of the study medication on either Bronchitis Severity Scores, change of symptoms and coughing frequency.

3.5.3 Acute cough

The treatment of acute cough with EA-575 (standardized extract from H. helix L.) was tested against placebo in one double blind randomized placebo controlled trial and reported a significantly better improvement of cough severity (CS) assessed by Visual Analogue Scale (VAS) in the intervention group after 1 week as compared to placebo ( Schaefer et al., 2016 ).

3.5.4 Acute lower and upper tract respiratory infections

We included one retrospective cohort study comparing people with acute lower and upper tract respiratory infections who were prescribed a phytopharmaceutical to those who were not prescribed such drugs. They found that extract EPs 7630 (description see 3.5.1) (odds ratio (OR) 0.49 [95% CI: 0.43–0.57]) and thyme extract (OR 0.62 [0.49–0.76]) compared to no phytopharmaceutical prescription exhibited the strongest decrease in antibiotics prescriptions among patients treated by general practitioners ( Martin et al., 2020 ).

4 Discussion

The aim of this review is to depict the current evidence for the therapeutic efficacy of herbal medicines. Therefore, we conducted a literature search with defined inclusion and exclusion criteria in particular to select information from clinical studies with high levels of evidence and legally approved (in Europe) herbal medicines. Certainly, life-threatening disease are not suitable for the treatment with herbal medicines. This is the reason why we limited our perspective on psychosomatic disorders, gynecological complaints, gastrointestinal disorders and common infectious diseases of the urinary and the upper respiratory tract. Additionally, we concentrated on clinical trials with adult patients. It is to be emphasized that respective studies using herbal drugs have also been done in children with psychosomatic diseases ( Verlaet et al., 2017 ; Schloss et al., 2021 ), IBS ( Menon et al., 2023 ), gastrointestinal disorders ( Michael et al., 2022 ), UTIs ( Ching, 2022 ), and URIs ( Mancak Karakus et al., 2023 ) to mention only some examples.

The use of herbal medicines in the treatment of psychosomatic disorders is widespread and accordingly a high number of clinical studies was available for our analysis. In our literature search, the term “psychosomatic disorders” has been chosen. This term has not been clearly defined but is related to diseases which involve both physical and psychological illness. In other words, the respective symptoms are caused by mental processes and not directly by a physical disorder. The hits we got are based on this “terminology”. In contrast, the term “mental illnesses” which also includes psychological or behavioral manifestations is strictly defined as “health conditions with changes in emotion, thinking or behavior” ( Stein et al., 2021 ). However, even this definition is problematic, since there are concerns about specific conditions, the discrimination between independent biological entities or value-laden social constructs, and the defined indicators of dysfunction ( Stein et al., 2021 ). Independent on these concerns, we did not apply this search term. Therefore, we cannot exclude that (very few) articles have not been discovered with our search strategy.

For the treatment of depressive disorders, St. John’s wort is well-established and the studies we selected were predominantly positive regarding improvement of symptoms. Concurrently, SJW is well tolerated and in the majority of the studies at least equal to conventional medication like tricyclic anti-depressants and selective serotonin reuptake inhibitors, which exhibit in part notable adverse events impacting patients’ quality of life of ( Voican et al., 2014 ; Jakobsen et al., 2017 ).

In contrast evidence for insomnia and anxiety was thinner. It would be worthwhile to study the use of herbal drugs as alternative medication for the treatment of sleeping disorders, as for elderly people or long term use conventional hypnotics are not always the best option ( Wortelboer et al., 2002 ; Cheng et al., 2020 ). All the studies we included were using valerian root extract alone or in combination with Humulus lupulus extract and showed positive effects on sleep without notable side effects. The few studies we selected for anxiety demonstrated efficacy of lavender extract (Lavandula angustifolia) and also here we had a homogenous picture of good efficacy along with good tolerability.

Several years ago, consistent beneficial effects of Ginkgo biloba for patients with cerebral insufficiency were proven in a systematic review ( Kleijnen and Knipschild, 1992 ). However, the methodologic quality of many trials was considered to be poor. Moreover, the studies entailed a heterogeneous collection of target health problems, ranging from overt dementia to noncognitive manifestations of brain dysfunction, such as vertigo and tinnitus. More recently, the results of several new Ginkgo biloba trials have been published, most of them focusing on dementia, and showing positive effects. Probably the most talked about is the trial of the North American EGb Study Group, which was published in the JAMA in 1997 and showed a modest improvement of the cognitive performance and the social functioning of the demented patients involved ( Le Bars et al., 1997 ), which is well in line with the studies we have collected.

In addition, menopausal symptoms and premenstrual syndrome are suitable for treatment with herbal medicines. In the here collected studies, no overall negative effects were observed and adverse events did not occur more frequently than in the comparison groups. A consistent picture emerged when comparing herbal treatment with synthetic drugs or placebo: while herbal drugs and treatment with, e.g., HRT or pyridoxine showed equal efficacy, herbal treatment was in general superior to placebo administration, except for one study.

Effective treatment of menopausal symptoms with black cohosh is supported with multiple study designs. Regardless of the study quality, there are no contradictory results.

The evidence for the treatment of PMS with VAC initially appears similar to that of black cohosh for menopausal symptoms. However, the sample sizes have been insufficient and there was a complete lack of comparisons of VAC with other therapies. Also of interest are the hints on the importance of the dose and continuous administration. A higher dosage did not have a higher efficacy compared to the standard dosage, but slightly more participants experienced adverse events ( Momoeda et al., 2014 ). This suggests a preference for the standard dosage of VAC. Continuous use of VAC is recommended, as it has been shown that symptoms increase significantly, even if they are still lower than before therapy ( Bachert et al., 2009 ).

However, further research is needed for both gynecological indications. Only one study each on sage for menopausal symptoms and SJW for premenstrual symptoms was found ( Lauritzen et al., 1997 ; Lauritzen et al., 1997 ; Adeyemo et al., 2013 ). The trend-setting results point to positive effects which have to be confirmed.

For gastrointestinal disorders herbal drugs were, at least partially, shown to be similar efficacious as the standard treatment. Selected, non-toxic plant derived natural compounds may, therefore, replace synthesized drugs which are associated with undesired negative side effects and the therapeutic potential of the compounds may depend on both the plant extract and the type of disease to be treated. Indeed, SJW was not efficacious in treating IBS, whereas WS 1340/WS 1520 and STW 5 and STW 5-II showed efficacy in both IBS and FD. Considering the broad spectrum of gastrointestinal complaints, therapy of severe liver disease may require more effort than treatment of moderate dyspepsia and, hence, herbal medicine may not replace standard therapy.

As no standard therapy has so far been established for FD ( Madisch et al., 2018 ) and IBS ( Lacy et al., 2021 ) the design of clinical studies is difficult, making it impossible to compare the phytodrug group with a “reference” cohort, and to finally assess the value of the phytodrugs.

Particular attention should be given to STW 5 containing greater celandine which has been related to liver and biliary tract disorders ( Zielińska et al., 2018 ). Therefore, careful preclinical examination of potential toxic properties of a compound of question is necessary before starting clinical trials.

Overall, most of the studies were well designed (multicenter, double-blind, placebo-controlled trials) with large cohorts. Considering the low side effects and often significant improvements, it might be useful to conduct further studies to either gain more detailed information about herbal medicine or to transfer the knowledge to diseases with a similar cluster of symptoms, so that distinct ailments might particularly benefit from herbal medicine ( Chey et al., 2015 ).

With respect to urinary tract infections (UTI), herbal medicines have been proven to be similar effective as antibiotics. Undoubtedly, the data encourages further research on herbal medicines as alternatives to antibiotics in acute lower uncomplicated UTI ( Wagenlehner et al., 2018 ). The use of herbal medicines has also been considered to be a good and safe alternative to perioperative antibiotic prophylaxis ( Miotla et al., 2018 ). However, whether herbal medicines may reduce or even replace antibiotics in future guideline-based regimen requires more prospective studies conducted on large groups of participants ( Wawrysiuk et al., 2022 ).

It is important to note in this context that one study discriminated between HM responders and non-responders ( Kulchavenya, 2018 ). This phenomenon is highly important, since it indicates that the application of HM in general might be restricted to a subset of patients. Unfortunately, no ongoing trials have been enrolled in this matter, and none of the publications cited here discussed the problem of acquired or innate resistance, at least from a theoretical point of view.

LUTS caused by BPH was treated differently than UTI, since the complications of BPH, namely, urinary incontinence, polyuria, urinary retention, and erectile dysfunction, have to be targeted. The clinical trials published so far point to the benefit of herbal medicines in reducing BPH symptoms. However, it is not clear yet whether the integration of herbal medicines may allow to reduce or even to avoid the use of standard medical therapeutics in this case.

Overall, several clinical studies conducted in the last years document a beneficial role of herbal medicines in the treatment of UTI and LUTS.

Upper Respiratory Infections (URIs) are a frequent cause of troublesome symptoms, that might be appropriately treated with herbal medicine. Most studies included in this paper evaluated herbal medicines for the treatment of acute bronchitis or common cold and acute sinusitis or rhinosinusitis.

The majority of the studies we included for the treatment of acute bronchitis tested P. sidoides against placebo and reported a statistically significant decrease of bronchitis symptoms and/severity. This is in line with the results of a systematic review and meta-analysis ( Agbabiaka et al., 2008 ), although a more recent systematic review judged that the evidence was of low quality ( Timmer et al., 2013 ). Evidence for other herbal medicines in the treatment of acute bronchitis was scarce.

For the treatment of common cold we found some indications of effectiveness of P. sidoides , Eucalyptus, sweet orange, myrtle and lemon oil (ELOM-080) and for Gentianae radix, Primulae flos, Sambuci flos, Rumicis herba and verbenae herba (BNO 1016). A recent systematic review with network meta-analysis, showed very little solid evidence of herbal medicine versus placebo for common cold, with only P. sidoides and Andrographis paniculata showing a reliable decrease of symptoms. Better results were found for herbal medicine versus placebo concerning health related quality of life (HRQoL) (in particular Spicae aetheroleum ) and for symptoms (Cineole and P. sidoides ) ( Hoang et al., 2023 ). A further systematic review reported on the efficacy of P. sidoides (liquid and tablet preparation) for the treatment of acute bronchitis, showing a positive results with, however, low evidence quality ( Timmer et al., 2013 ).

Although herbal medicines are considered to be safe in principle, this might not always be the case. Some herbal compounds are suspected to be carcinogenic and/or hepatotoxic. Herbal products have also been shown to inhibit and/or induce drug-metabolizing enzymes ( Moreira et al., 2014 ). This has to be taken into account, since herbal medicines are often used in combination with conventional drugs. In this context, preparations with SJW may reduce the efficacy of chemotherapy and of anticoagulants but enhance the one of certain consciousness-lowering agents (e.g., sedative medicines, antidepressants) ( Nicolussi et al., 2020 ; Scholz et al., 2021 ). Due to potential liver toxicity of chelidonium majus, preparations containing more than 2.5 mg daily dose of whole chelidonium alkaloids had to be withdrawn, and for all preparations with lower daily doses, their instruction leaflet must include warnings on liver toxicity ( Rosien, 2019 ). Therefore, the drug’s safety must always be carefully investigated and guaranteed by the producers and the regulatory authorities.

The analysis of the outcomes in the selected disorders reflects that herbal medicines are most efficacious for the treatment of URTI ( Figure 5 ), followed by gynecological complaints ( Figure 2 ) and psychosomatic disorders ( Figure 1 ). For the treatment of urological diseases ( Figure 4 ) in particular UTI and LUTS, we could select only 16 studies according to our strict inclusion/exclusion criteria and therefore more studies of high quality have to be performed to gain a better insight into the efficacy of herbal drugs for these ailments. Gastrointestinal diseases hold a special position as only the added value of the phytodrugs to the conventional therapy was tested. In addition, the number of studies we selected was small ( Figure 3 ), making it difficult to judge the efficacy of herbal drugs for this indication.

This report on the current state of research on the clinical benefits of herbal medicines for non-life-threatening ailments has some limitations.

• 1. The literature search had to be restricted to Pubmed, because other relevant databases like e.g., EMBASE or CINAHL have not been accessible to the authors.
• 2. Further limitations are the small cohorts in some of the studies
• 3. Or that the results/outcomes of some studies have been re-analyzed from previous studies.
• 4. A general obstacle of data interpretation is that for some indications, in particular for gastrointestinal diseases, herbal medicines are predominantly co-administered with standard therapy, which makes it difficult to estimate the clinical benefit of the phytodrug alone.

5 Perspective

Our literature research gives insights into applied herbal medicines for selected indications, the study outcomes and their quality. Based on our results, we (the authors) provide an overview for patients and healthcare practitioners which extracts can be recommended for the treatment if which disorder/complaint ( Supplementary Table S1 ).

In this context we recommend in particular H. perforatum L. for depressive disorder, V. agnus castus L. for menstrual complaints, Cimicifica racemose (L.) for menopausal symptoms, a combination of I. amara L., M. chamomilla L., Mentha × piperita L., C. carvi L., G. glabra L. and M. officinalis L., for functional dyspepsia, a combination of C. erythraea , Levisticum officinale W.D.J.Koch and Rosmarinus officinalis L. for uncomlicated urinary tract infections, P. sidoides DC. for bronchitis and sinusitis and finally H. helix for cough ( Supplementary Table S1 ). These recommendations are based on studies with the highest levels of evidence (RCTs).

However, evidence for efficacy of herbal medicines is still not satisfying in order to integrate them in conventional medicine guidelines and standard treatment regimen, which is the reason why statutory health insurances do not reimburse the costs. In fact, herbal medicines are highly popular and accepted among patients, since their application is safe since they do not exert severe side-effects. Especially when conventional medical therapies fail due to undesired side effects having a negative impact on the quality of life, patients are willing to purchase herbal medicines at their own expense. Often doctors do not know about the self-medication activities of their patients and in consequence cannot monitor the treatment with herbal medicines and possible interactions with other drugs.

The discrepancy between available results from clinical research and the use of herbal medicines under everyday conditions shows that we need to perform more interdisciplinary research studies in the future in order to collect scientific sound evidence on their benefits. Clinical research can provide information on the efficacy of phytodrugs and the importance of genetic dispositions and metabolism as well as possible interactions with other medicines. For effectiveness under everyday conditions (from bedside to practice), methods of health services research are necessary. With the help of these, the outcomes of herbal medicines can be recorded from different perspectives, in particular those of the patients (patient-reported outcomes (PROs)). For longitudinal observations, analyses of health insurance and sales volume data are also relevant, using prescriptions and the over-the-counter sales to get a picture on the needs of the patients and the acceptance of phytotherapy by healthcare practitioners. In order to pave the way for the integration of herbal medicines into therapy guidelines and regimens, findings from clinical studies should be carefully evaluated for their transferability to everyday healthcare within the scope of health services research. This way could lead to novel rational efficacious therapy strategies with less side-effects and better compliance of the patients.

Data availability statement

Author contributions.

SS: Investigation, Formal analysis, Writing–Original Draft. JR: Investigation, Formal analysis, Writing–Original Draft, Visualization. MA: Methodology, Investigation, Formal analysis, Writing–Original Draft. RB: Investigation, Formal analysis, Writing–Original Draft. BB: Conceptualization, Methodology, Investigation, Formal analysis, Writing–Original Draft, Supervision. All authors contributed to the article and approved the submitted version.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Supplementary material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fphar.2023.1234701/full#supplementary-material

• Adeyemo O., Doi H., Rajender Reddy K., Kaplan D. E. (2013). Impact of oral silymarin on virus- and non-virus-specific T-cell responses in chronic hepatitis C infection . J. Viral Hepat. 20 , 453–462. 10.1111/jvh.12050 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Agbabiaka T. B., Guo R., Ernst E. (2008). Pelargonium sidoides for acute bronchitis: A systematic review and meta-analysis . Phytomedicine 15 , 378–385. 10.1016/j.phymed.2007.11.023 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Albrecht U., Goos K. H., Schneider B. (2007). A randomised, double-blind, placebo-controlled trial of a herbal medicinal product containing Tropaeoli majoris herba (Nasturtium) and Armoraciae rusticanae radix (Horseradish) for the prophylactic treatment of patients with chronically recurrent lower urinary tract infections . Curr. Med. Res. Opin. 23 , 2415–2422. 10.1185/030079907X233089 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Anghelescu I. G., Kohnen R., Szegedi A., Klement S., Kieser M. (2006). Comparison of Hypericum extract WS 5570 and paroxetine in ongoing treatment after recovery from an episode of moderate to severe depression: Results from a randomized multicenter study . Pharmacopsychiatry 39 , 213–219. 10.1055/s-2006-951388 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Armour M., Ee C. C., Hao J., Wilson T. M., Yao S. S., Smith C. A. (2018). Acupuncture and acupressure for premenstrual syndrome . Cochrane Database Syst. Rev. 8 , CD005290. 10.1002/14651858.CD005290.pub2 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• AWMF (2020). Peri- and postmenopause – diagnosis and interventions. Guideline of the DGGG, SGGG and OEGGG (S3 level, AWMF registry No. 015-062, january 2020) . Marburg, Germany: Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V. [ Google Scholar ]
• Bachert C., Schapowal A., Funk P., Kieser M. (2009). Treatment of acute rhinosinusitis with the preparation from Pelargonium sidoides EPs 7630: A randomized, double-blind, placebo-controlled trial . Rhinology 47 , 51–58. [ PubMed ] [ Google Scholar ]
• Bachmeier B. E., Iancu C. M., Killian P. H., Kronski E., Mirisola V., Angelini G., et al. (2009). Overexpression of the ATP binding cassette gene ABCA1 determines resistance to Curcumin in M14 melanoma cells . Mol. Cancer 8 , 129. 10.1186/1476-4598-8-129 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Bachmeier B. E., Mirisola V., Romeo F., Generoso L., Esposito A., Dell'eva R., et al. (2010). Reference profile correlation reveals estrogen-like trancriptional activity of Curcumin . Cell Physiol. Biochem. 26 , 471–482. 10.1159/000320570 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Bachmeier B. E., Mohrenz I. V., Mirisola V., Schleicher E., Romeo F., Hohneke C., et al. (2008). Curcumin downregulates the inflammatory cytokines CXCL1 and -2 in breast cancer cells via NFkappaB . Carcinogenesis 29 , 779–789. 10.1093/carcin/bgm248 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Bachmeier B., Nerlich A. G., Iancu C. M., Cilli M., Schleicher E., Vene R., et al. (2007). The chemopreventive polyphenol Curcumin prevents hematogenous breast cancer metastases in immunodeficient mice . Cell Physiol. Biochem. 19 , 137–152. 10.1159/000099202 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Bai W., Henneicke-Von Zepelin H. H., Wang S., Zheng S., Liu J., Zhang Z., et al. (2007). Efficacy and tolerability of a medicinal product containing an isopropanolic black cohosh extract in Chinese women with menopausal symptoms: A randomized, double blind, parallel-controlled study versus tibolone . Maturitas 58 , 31–41. 10.1016/j.maturitas.2007.04.009 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Barrett B., Brown R., Rakel D., Mundt M., Bone K., Barlow S., et al. (2010). Echinacea for treating the common cold: A randomized trial . Ann. Intern. Med. 153 , 769–777. 10.7326/0003-4819-153-12-201012210-00003 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Barrett B. P., Brown R. L., Locken K., Maberry R., Bobula J. A., D'alessio D. (2002). Treatment of the common cold with unrefined echinacea. A randomized, double-blind, placebo-controlled trial . Ann. Intern Med. 137 , 939–946. 10.7326/0003-4819-137-12-200212170-00006 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Berger D., Schaffner W., Schrader E., Meier B., Brattstrom A. (2000). Efficacy of Vitex agnus castus L. extract Ze 440 in patients with pre-menstrual syndrome (PMS) . Arch. Gynecol. Obstet. 264 , 150–153. 10.1007/s004040000123 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Bittel M., Rakoczy T., Fröhlich A., Langhorst J. (2022). Phytotherapie bei psychischen Erkrankungen in medizinischen Leitlinien . Z. für Phytother. 43 , 112–120. 10.1055/a-1716-9651 [ CrossRef ] [ Google Scholar ]
• Bjerkenstedt L., Edman G. V., Alken R. G., Mannel M. (2005). Hypericum extract LI 160 and fluoxetine in mild to moderate depression: A randomized, placebo-controlled multi-center study in outpatients . Eur. Arch. Psychiatry Clin. Neurosci. 255 , 40–47. 10.1007/s00406-004-0532-z [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Bommer S., Klein P., Suter A. (2011). First time proof of sage's tolerability and efficacy in menopausal women with hot flushes . Adv. Ther. 28 , 490–500. 10.1007/s12325-011-0027-z [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Brenner R., Azbel V., Madhusoodanan S., Pawlowska M. (2000). Comparison of an extract of hypericum (li 160) and sertraline in the treatment of depression: A double-blind, randomized pilot study . Clin. Ther. 22 , 411–419. 10.1016/S0149-2918(00)89010-4 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Briese V., Stammwitz U., Friede M., Henneicke-Von Zepelin H. H. (2007). Black cohosh with or without St. John's wort for symptom-specific climacteric treatment-results of a large-scale, controlled, observational study . Maturitas 57 , 405–414. 10.1016/j.maturitas.2007.04.008 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Burkhardt H., Wehling M. (2010). [ Difficulties in pharmacotherapy of the elderly ]. Der Internist 51 , 737–747. 10.1007/s00108-010-2582-9 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Canning S., Waterman M., Orsi N., Ayres J., Simpson N., Dye L. (2010). The efficacy of Hypericum perforatum (St john's wort) for the treatment of premenstrual syndrome: A randomized, double-blind, placebo-controlled trial . CNS Drugs 24 , 207–225. 10.2165/11530120-000000000-00000 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Cheng B., Liu Y., Tian J., Gao R., Liu Y. (2020). Complementary and alternative medicine for the treatment of insomnia: An overview of scientific evidence from 2008 to 2018 . Curr. Vasc. Pharmacol. 18 , 307–321. 10.2174/1570161117666190506111239 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Chey W. D., Kurlander J., Eswaran S. (2015). Irritable bowel syndrome: A clinical review . JAMA 313 , 949–958. 10.1001/jama.2015.0954 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Ching C. B. (2022). Non-antibiotic approaches to preventing pediatric UTIs: A role for D-mannose, cranberry, and probiotics? Curr. Urol. Rep. 23 , 113–127. 10.1007/s11934-022-01094-w [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Chuchalin A. G., Berman B., Lehmacher W. (2005). Treatment of acute bronchitis in adults with a pelargonium sidoides preparation (EPs 7630): A randomized, double-blind, placebo-controlled trial . Explore (New York, N.Y.) 1 , 437–445. 10.1016/j.explore.2005.08.009 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Cornberg M., Wedemeyer H., Manns M. P. (2002). Treatment of chronic hepatitis C with PEGylated interferon and ribavirin . Curr. Gastroenterol. Rep. 4 , 23–30. 10.1007/s11894-002-0034-y [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Corrao S., Scaglione R., Calvo L., Licata G. (2007). Methodological matters on an alzheimer's dementia trial: Is a double-blind randomized controlled study design sufficient to draw strong conclusions on treatment? Reply to Dr mazza and colleagues . Eur. J. Neurology 14 , e11; author reply e12–e11. 10.1111/j.1468-1331.2007.01713.x [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Darbinyan V., Aslanyan G., Amroyan E., Gabrielyan E., Malmstrom C., Panossian A. (2007). Clinical trial of Rhodiola rosea L. extract SHR-5 in the treatment of mild to moderate depression . Nordic J. Psychiatry 61 , 343–348. 10.1080/08039480701643290 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Davidson J. R. T., Gadde K. M., Fairbank J. A., Krishnan R. R., Califf R. M., Binanay C., et al. (2002). Effect of Hypericum perforatum (St John's wort) in major depressive disorder - a randomized controlled trial . Jama 287 , 1807–1814. 10.1001/jama.287.14.1807 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Dejaco D., Bocian-Sobkowska J., Szymanski W., Zacke G., Hockner V., Riechelmann H. (2019). Tavipec in acute rhinosinusitis: A multi-centre, doubleblind, randomized, placebo-controlled, clinical trial . Rhinology 57 , 367–374. 10.4193/Rhin19.089 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Donath F., Quispe S., Diefenbach K., Maurer A., Fietze I., Roots I. (2000). Critical evaluation of the effect of valerian extract on sleep structure and sleep quality . Pharmacopsychiatry 33 , 47–53. 10.1055/s-2000-7972 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Dorn M. (2000). Efficacy and tolerability of baldrian versus oxazepam in non-organic and non-psychiatric insomniacs: A randomised, double-blind, clinical, comparative study . Forsch Komplementarmed Klass. Naturheilkd 7 , 79–84. 10.1159/000021314 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Drewe J., Zimmermann C., Zahner C. (2013). The effect of a Cimicifuga racemosa extracts Ze 450 in the treatment of climacteric complaints-an observational study . Phytomedicine 20 , 659–666. 10.1016/j.phymed.2013.02.012 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Engelmann U., Walther C., Bondarenko B., Funk P., Schläfke S. (2011). Efficacy and safety of a combination of sabal and urtica extract in lower urinary tract symptoms. A randomized, double-blind study versus tamsulosin . Arzneimittelforschung 56 , 222–229. 10.1055/s-0031-1296714 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Fathalah W. F., Aziz M. A., Abou El Soud N. H., El Raziky M. E. (2017). High dose of silymarin in patients with decompensated liver disease: A randomized controlled trial . J. Interferon Cytokine Res. 37 , 480–487. 10.1089/jir.2017.0051 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Fava M., Alpert J., Nierenberg A. A., Mischoulon D., Otto M. W., Zajecka J., et al. (2005). A double-blind, randomized trial of St John's wort, fluoxetine, and placebo in major depressive disorder . J. Clin. Psychopharmacol. 25 , 441–447. 10.1097/01.jcp.0000178416.60426.29 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Fazio S., Pouso J., Dolinsky D., Fernandez A., Hernandez M., Clavier G., et al. (2009). Tolerance, safety and efficacy of Hedera helix extract in inflammatory bronchial diseases under clinical practice conditions: A prospective, open, multicentre postmarketing study in 9657 patients . Phytomedicine 16 , 17–24. 10.1016/j.phymed.2006.05.003 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Feagan B. G., Rochon J., Fedorak R. N., Irvine E. J., Wild G., Sutherland L., et al. (1995). Methotrexate for the treatment of crohn's disease. The North American crohn's study group investigators . N. Engl. J. Med. 332 , 292–297. 10.1056/NEJM199502023320503 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Federspil P., Wulkow R., Zimmermann T. (1997). [ Effects of standardized Myrtol in therapy of acute sinusitis-results of a double-blind, randomized multicenter study compared with placebo ]. Laryngo- rhino- Otol. 76 , 23–27. 10.1055/s-2007-997381 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Ferenci P., Scherzer T. M., Hofer H., Schniger-Hekele M., Steindl-Munda P. (2008). Silibinin is a potent antiviral agent in patients with chronic hepatitis C not responding to antiviral combination therapy . J. Hepatology 48 , S28. 10.1016/s0168-8278(08)60065-3 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Ford O., Mol B., Roberts H., Ford O. (2006). Progesterone for premenstrual syndrome . Cochrane Database Syst. Rev. 2012 , CD003415. 10.1002/14651858.CD003415.pub4 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Fried M. W., Navarro V. J., Afdhal N., Belle S. H., Wahed A. S., Hawke R. L., et al. (2012). Effect of silymarin (milk thistle) on liver disease in patients with chronic hepatitis C unsuccessfully treated with interferon therapy: A randomized controlled trial . JAMA 308 , 274–282. 10.1001/jama.2012.8265 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Friede M., Von Zepelin H. H. H., Freudenstein J. (2001). Differential therapy of mild to moderate depressive episodes (ICD-10 F 32.0; F 32.1) with St. John's wort . Pharmacopsychiatry 34 , S38–S41. 10.1055/s-2001-15459 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Friederichsen L., Nebel S., Zahner C., Butikofer L., Stute P. (2020). Effect of CIMicifuga racemosa on metaBOLIC parameters in women with menopausal symptoms: A retrospective observational study (CIMBOLIC) . Archives Gynecol. Obstetrics 301 , 517–523. 10.1007/s00404-019-05366-8 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Fries C. J. (2019). Healing health care: From sick care towards salutogenic healing systems . Soc. Theory and Health 18 , 16–32. 10.1057/s41285-019-00103-2 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Gastpar M., Singer A., Zeller K. (2006). Comparative efficacy and safety of a once-daily dosage of hypericum extract STW3-VI and citalopram in patients with moderate depression: A double-blind, randomised, multicentre, placebo-controlled study . Pharmacopsychiatry 39 , 66–75. 10.1055/s-2006-931544 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Gastpar M., Singer A., Zeller K. (2005). Efficacy and tolerability of hypericum extract STW3 in long-term treatment with a once-daily dosage in comparison with sertraline . Pharmacopsychiatry 38 , 78–86. 10.1055/s-2005-837807 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Gauruder-Burmester A., Heim S., Patz B., Seibt S. (2019). Cucurbita pepo-rhus aromatica-humulus lupulus combination reduces overactive bladder symptoms in women - a noninterventional study . Planta Med. 85 , 1044–1053. 10.1055/a-0946-2280 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Gavrilova S. I., Preuss U. W., Wong J. W., Hoerr R., Kaschel R., Bachinskaya N., et al. (2014). Efficacy and safety of ginkgo biloba extract EGb 761 in mild cognitive impairment with neuropsychiatric symptoms: A randomized, placebo-controlled, double-blind, multi-center trial . Int. J. Geriatr. Psychiatry 29 , 1087–1095. 10.1002/gps.4103 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Gillissen A., Wittig T., Ehmen M., Krezdorn H. G., Mey C. D. (2013). A multi-centre, randomised, double-blind, placebo-controlled clinical trial on the efficacy and tolerability of GeloMyrtol® forte in acute bronchitis . Drug Res. 63 , 19–27. 10.1055/s-0032-1331182 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Goel V., Lovlin R., Barton R., Lyon M. R., Bauer R., Lee T. D., et al. (2004). Efficacy of a standardized echinacea preparation (echinilin) for the treatment of the common cold: A randomized, double-blind, placebo-controlled trial . J. Clin. Pharm. Ther. 29 , 75–83. 10.1111/j.1365-2710.2003.00542.x [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Gottschlich S., Röschmann K., Candler H. (2018). Phytomedicines in acute rhinosinusitis: A prospective, non-interventional parallel-group trial . Adv. Ther. 35 , 1023–1034. 10.1007/s12325-018-0736-7 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Gründer G., Benkert O. (2012). Handbuch der Psychopharmakotherapie . Berlin, Heidelberg: Springer. [ Google Scholar ]
• Grunze A., Mago R., Grunze H. (2017). [ Side effects of psychotropic medication: Suggestions for clinical practice ]. DMW - Dtsch. Med. Wochenschr. 142 , 1690–1700. 10.1055/s-0043-110654 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Gschwind Y., Bridenbaugh S., Reinhard S., Granacher U., Monsch A., Kressig R. (2017). Ginkgo biloba special extract LI 1370 improves dual-task walking in patients with MCI: A randomised, double-blind, placebo-controlled exploratory study . Aging Clin. Exp. Res. 29 , 609–619. 10.1007/s40520-016-0699-y [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Hansgen K. D., Vesper J., Ploch M. (1994). Multicenter double-blind study examining the antidepressant effectiveness of the hypericum extract LI 160 . J. Geriatr. Psychiatry Neurol. 7 ( 1 ), S15–S18. 10.1177/089198879400700106 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Harrer G., Hubner W. D., Podzuweit H. (1994). Effectiveness and tolerance of the hypericum extract LI 160 compared to maprotiline: A multicenter double-blind study . J. Geriatr. Psychiatry Neurol. 7 ( 1 ), S24–S28. 10.1177/089198879400700108 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Harrer G., Schmidt U., Kuhn U., Biller A. (1999). Comparison of equivalence between the St. John's wort extract LoHyp-57 and fluoxetine . Arzneimittelforschung-Drug Res. 49 , 289–296. 10.1055/s-0031-1300417 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Haupt M., Vollmar H. C. (2008). “ Psychische Erkrankungen bei älteren Patienten ,” in Psychische erkrankungen in der Hausarztpraxis . Editors Schneider F, Niebling W. (Berlin, Heidelberg: Springer; ), 517–532. [ Google Scholar ]
• Hawke R. L., Schrieber S. J., Soule T. A., Wen Z. M., Smith P. C., Reddy K. R., et al. (2010). Silymarin ascending multiple oral dosing phase I study in noncirrhotic patients with chronic hepatitis C . J. Clin. Pharmacol. 50 , 434–449. 10.1177/0091270009347475 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Hecker M., Runkel F., Voelp A. (2002). [ Treatment of chronic bronchitis with ivy leaf special extract-multicenter post-marketing surveillance study in 1,350 patients ]. Forsch. Komplementarmedizin Klass. Naturheilkd. 9 , 77–84. 10.1159/000057269 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Hoang M. P., Seresirikachorn K., Chitsuthipakorn W., Snidvongs K. (2023). Herbal medicines for rhinosinusitis: A systematic review and network meta-analysis . Curr. Allergy Asthma Rep. 23 , 93–109. 10.1007/s11882-022-01060-z [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Holler M., Steindl H., Abramov-Sommariva D., Wagenlehner F., Naber K. G., Kostev K. (2021). Treatment of urinary tract infections with Canephron ® in Germany: A retrospective database analysis . Antibiot. (Basel) 10 , 685. 10.3390/antibiotics10060685 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Huber R., Ditfurth A. V., Amann F., Güthlin C., Rostock M., Trittler R., et al. (2007). Tormentil for active ulcerative colitis: An open-label, dose-escalating study . J. Clin. Gastroenterology 41 , 834–838. 10.1097/MCG.0b013e31804b2173 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Jakobsen J. C., Katakam K. K., Schou A., Hellmuth S. G., Stallknecht S. E., Leth-Møller K., et al. (2017). Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and Trial Sequential Analysis . BMC Psychiatry 17 , 58. 10.1186/s12888-016-1173-2 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Jaume F., Valls-Mateus M., Mullol J. (2020). Common cold and acute rhinosinusitis: Up-to-Date management in 2020 . Curr. Allergy Asthma Rep. 20 , 28. 10.1007/s11882-020-00917-5 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Julia Molla M. D., Garcia-Sanchez Y., Romeu Sarri A., Perez-Lopez F. R. (2009). Cimicifuga racemosa treatment and health related quality of life in post-menopausal Spanish women . Gynecol. Endocrinol. 25 , 21–26. 10.1080/09513590802404005 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Jund R., Mondigler M., Stammer H., Stierna P., Bachert C. (2015). Herbal drug BNO 1016 is safe and effective in the treatment of acute viral rhinosinusitis . Acta oto-laryngologica 135 , 42–50. 10.3109/00016489.2014.952047 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Jung N., Tometten L., Draenert R. (2023). Choosing Wisely internationally – helpful recommendations for antimicrobial stewardship! . Infection 51 , 567–581. 10.1007/s15010-023-02005-y [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Kähler C., Derezinski T., Bocian-Sobkowska J., Keckeis A., Zacke G. (2019). Spicae aetheroleum in uncomplicated acute bronchitis: A double-blind, randomised clinical trial . Wien. Med. Wochenschr. 169 , 137–148. 10.1007/s10354-017-0612-0 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Kalb R., Trautmann-Sponsel R. D., Kieser M. (2001). Efficacy and tolerability of Hypericum extract WS 5572 versus placebo in mildly to moderately depressed patients - a randomized double-blind multicenter clinical trial . Pharmacopsychiatry 34 , 96–103. 10.1055/s-2001-14280 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Kasper S., Anghelescu I., Dienel A. (2015). Efficacy of orally administered Silexan in patients with anxiety-related restlessness and disturbed sleep-A randomized, placebo-controlled trial . Eur. Neuropsychopharmacol. 25 , 1960–1967. 10.1016/j.euroneuro.2015.07.024 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Kasper S., Anghelescu I. G., Szegedi A., Dienel A., Kieser M. (2007). Placebo controlled continuation treatment with Hypericum extract WS 5570 after recovery from a mild or moderate depressive episode . Wien Med. Wochenschr 157 , 362–366. 10.1007/s10354-007-0441-7 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Kasper S., Anghelescu I. G., Szegedi A., Dienel A., Kieser M. (2006). Superior efficacy of St john's wort extract WS 5570 compared to placebo in patients with major depression: A randomized, double-blind, placebo-controlled, multi-center trial [ISRCTN77277298] . BMC Med. 4 , 14. 10.1186/1741-7015-4-14 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Kasper S., Gastpar M., Muller W. E., Volz H. P., Moller H. J., Dienel A., et al. (2010). Silexan, an orally administered Lavandula oil preparation, is effective in the treatment of 'subsyndromal' anxiety disorder: A randomized, double-blind, placebo controlled trial . Int. Clin. Psychopharmacol. 25 , 277–287. 10.1097/YIC.0b013e32833b3242 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Kasper S., Gastpar M., Muller W. E., Volz H. P., Moller H. J., Schlafke S., et al. (2014). Lavender oil preparation Silexan is effective in generalized anxiety disorder - a randomized, double-blind comparison to placebo and paroxetine . Int. J. Neuropsychopharmacol. 17 , 859–869. 10.1017/S1461145714000017 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Kasper S., Volz H. P., Dienel A., Schlafke S. (2016). Efficacy of Silexan in mixed anxiety-depression-A randomized, placebo-controlled trial . Eur. Neuropsychopharmacol. 26 , 331–340. 10.1016/j.euroneuro.2015.12.002 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Kasper S., Volz H. P., Moller H. J., Dienel A., Kieser M. (2008). Continuation and long-term maintenance treatment with Hypericum extract WS 5570 after recovery from an acute episode of moderate depression-a double-blind, randomized, placebo controlled long-term trial . Eur. Neuropsychopharmacol. 18 , 803–813. 10.1016/j.euroneuro.2008.06.006 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Killian P. H., Kronski E., Michalik K. M., Barbieri O., Astigiano S., Sommerhoff C. P., et al. (2012). Curcumin inhibits prostate cancer metastasis in vivo by targeting the inflammatory cytokines CXCL1 and -2 . Carcinogenesis 33 , 2507–2519. 10.1093/carcin/bgs312 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Kleijnen J., Knipschild P. (1992). Ginkgo biloba . Lancet 340 , 1136–1139. 10.1016/0140-6736(92)93158-j [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Koetter U., Schrader E., Kaufeler R., Brattstrom A. (2007). A randomized, double blind, placebo-controlled, prospective clinical study to demonstrate clinical efficacy of a fixed valerian hops extract combination (Ze 91019) in patients suffering from non-organic sleep disorder . Phytother. Res. 21 , 847–851. 10.1002/ptr.2167 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Korczyn A. D. (2007). Comments on the article by mazza et al. Concerning ginkgo biloba and donepezil: A comparison in the treatment of alzheimer's dementia in a randomized placebo-controlled double-blind study . Eur. J. Neurol. 14 , e9; author reply e10. 10.1111/j.1468-1331.2007.01710.x [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Krebs S., Omer T. N., Omer B. (2010). Wormwood (Artemisia absinthium) suppresses tumour necrosis factor alpha and accelerates healing in patients with Crohn’s disease – a controlled clinical trial . Phytomedicine 17 , 305–309. 10.1016/j.phymed.2009.10.013 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Kronski E., Fiori M. E., Barbieri O., Astigiano S., Mirisola V., Killian P. H., et al. (2014). miR181b is induced by the chemopreventive polyphenol curcumin and inhibits breast cancer metastasis via down-regulation of the inflammatory cytokines CXCL1 and -2 . Mol. Oncol. 8 , 581–595. 10.1016/j.molonc.2014.01.005 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Kulchavenya E. (2018). Acute uncomplicated cystitis: Is antibiotic unavoidable? Ther. Adv. Urol. 10 , 257–262. 10.1177/1756287218783644 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Kwan I., Onwude J. L. (2015). Premenstrual syndrome . BMJ Clin. Evid. 2015 , 0806. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Laakmann G., Schule C., Baghai T., Kieser M. (1998). St. John's wort in mild to moderate depression: The relevance of hyperforin for the clinical efficacy . Pharmacopsychiatry 31 ( 1 ), 54–59. 10.1055/s-2007-979346 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Lacy B. E., Pimentel M., Brenner D. M., Chey W. D., Keefer L. A., Long M. D., et al. (2021). ACG clinical guideline: Management of irritable bowel syndrome . Am. J. Gastroenterology 116 , 17–44. 10.14309/ajg.0000000000001036 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Lauritzen C., Reuter H. D., Repges R., Bohnert K. J., Schmidt U. (1997). Treatment of premenstrual tension syndrome with Vitex agnus castus controlled, double-blind study versus pyridoxine . Phytomedicine 4 , 183–189. 10.1016/S0944-7113(97)80066-9 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Laux G. (2021). “ Psychopharmakotherapie ,” in Duale Reihe Psychiatrie, Psychosomatik und Psychotherapie . Editors Falkai P. L, Gerd L., Deister A, Möller H. J. 7 ed (New York: Thieme; ). [ Google Scholar ]
• Le Bars P. L. (2003). Response patterns of EGb 761 in alzheimer's disease: Influence of neuropsychological profiles . Pharmacopsychiatry 36 ( 1 ), S50–S55. 10.1055/s-2003-40456 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Le Bars P. L., Katz M. M., Berman N., Itil T. M., Freedman A. M., Schatzberg A. F. (1997). A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. North American EGb Study Group . JAMA 278 , 1327–1332. 10.1001/jama.278.16.1327 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Le Bars P. L., Velasco F. M., Ferguson J. M., Dessain E. C., Kieser M., Hoerr R. (2002). Influence of the severity of cognitive impairment on the effect of the Ginkgo biloba extract EGb 761 ® in Alzheimer’s disease . Neuropsychobiology 45 , 19–26. 10.1159/000048668 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Lecrubier Y., Clerc G., Didi R., Kieser M. (2002). Efficacy of St. John's wort extract WS 5570 in major depression: A double-blind, placebo-controlled trial . Am. J. Psychiatry 159 , 1361–1366. 10.1176/appi.ajp.159.8.1361 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Liske E., Hanggi W., Henneicke-Von Zepelin H. H., Boblitz N., Wustenberg P., Rahlfs V. W. (2002). Physiological investigation of a unique extract of black cohosh (cimicifugae racemosae rhizoma): A 6-month clinical study demonstrates no systemic estrogenic effect . J. Womens Health Gend. Based Med. 11 , 163–174. 10.1089/152460902753645308 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Loch E. G., Selle H., Boblitz N. (2000). Treatment of premenstrual syndrome with a phytopharmaceutical formulation containing Vitex agnus castus . J. Womens Health Gend. Based Med. 9 , 315–320. 10.1089/152460900318515 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Lopatkin N., Sivkov A., Schlafke S., Funk P., Medvedev A., Engelmann U. (2007). Efficacy and safety of a combination of Sabal and Urtica extract in lower urinary tract symptoms-long-term follow-up of a placebo-controlled, double-blind, multicenter trial . Int. Urol. Nephrol. 39 , 1137–1146. 10.1007/s11255-006-9173-7 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Lopatkin N., Sivkov A., Walther C., Schlafke S., Medvedev A., Avdeichuk J., et al. (2005). Long-term efficacy and safety of a combination of sabal and urtica extract for lower urinary tract symptoms-a placebo-controlled, double-blind, multicenter trial . World J. Urol. 23 , 139–146. 10.1007/s00345-005-0501-9 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Lopez L. M., Kaptein A., Helmerhorst F. M., Lopez L. (2007). Oral contraceptives containing drospirenone for premenstrual syndrome . Cochrane Database Syst. Rev. 15 , CD006586. 10.1002/14651858.CD006586.pub4 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Maclennan A. H., Broadbent J. L., Lester S., Moore V. (2004). Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes . Cochrane database Syst. Rev. 2004 , CD002978. 10.1002/14651858.CD002978.pub2 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Madersbacher S., Rieken M., Reuber K., Kostev K. (2023). Association between PRO 160/120 prescriptions and incidence of benign prostatic hyperplasia complications in Germany: A retrospective cohort study . Postgrad. Med. 135 , 149–154. 10.1080/00325481.2022.2149156 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Madisch A., Andresen V., Enck P., Labenz J., Frieling T., Schemann M. (2018). The diagnosis and treatment of functional dyspepsia . Dtsch. Ärzteblatt Int. 115 , 222–232. 10.3238/arztebl.2018.0222 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Madisch A., Heydenreich C. J., Wieland V., Hufnagel R., Hotz J. (1999). Treatment of functional dyspepsia with a fixed peppermint oil and caraway oil combination preparation as compared to cisapride - a multicenter, reference-controlled double-blind equivalence study . Arzneimittel-Forschung-Drug Res. 49 , 925–932. 10.1055/s-0031-1300528 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Madisch A., Holtmann G., Mayr G., Vinson B., Hotz J. (2004a). Treatment of functional dyspepsia with a herbal preparation. A double-blind, randomized, placebo-controlled, multicenter trial . Digestion 69 , 45–52. 10.1159/000076546 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Madisch A., Holtmann G., Plein K., Hotz J. (2004b). Treatment of irritable bowel syndrome with herbal preparations: Results of a double-blind, randomized, placebo-controlled, multi-centre trial . Aliment. Pharmacol. Ther. 19 , 271–279. 10.1111/j.1365-2036.2004.01859.x [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Mancak Karakus M., Tapisiz A., Mutlu Karakas N., Deniz M., Koca Caliskan U. (2023). Use of herbal tea/herbal preparations for children with symptoms of viral upper respiratory infections . Turk J. Pharm. Sci. 20 , 8–15. 10.4274/tjps.galenos.2022.65475 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Mannel M., Kuhn U., Schmidt U., Ploch M., Murck H. (2010). St. John's wort extract LI160 for the treatment of depression with atypical features - a double-blind, randomized, and placebo-controlled trial . J. Psychiatr. Res. 44 , 760–767. 10.1016/j.jpsychires.2010.01.010 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Mao J. J., Xie S. X., Zee J., Soeller I., Li Q. S., Rockwell K., et al. (2015). Rhodiola rosea versus sertraline for major depressive disorder: A randomized placebo-controlled trial . Phytomedicine 22 , 394–399. 10.1016/j.phymed.2015.01.010 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Marjoribanks J., Brown J., O'brien P. M. S., Wyatt K. (2013). Selective serotonin reuptake inhibitors for premenstrual syndrome . Cochrane Database Syst. Rev. 2013 , CD001396. 10.1002/14651858.CD001396.pub3 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Martin D., Konrad M., Adarkwah C. C., Kostev K. (2020). Reduced antibiotic use after initial treatment of acute respiratory infections with phytopharmaceuticals-a retrospective cohort study . Postgrad. Med. 132 , 412–418. 10.1080/00325481.2020.1751497 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Matthys H., Eisebitt R., Seith B., Heger M. (2003). Efficacy and safety of an extract of Pelargonium sidoides (EPs 7630) in adults with acute bronchitis. A randomised, double-blind, placebo-controlled trial . Phytomedicine Int. J. phytotherapy Phytopharm. 10 ( 4 ), 7–17. 10.1078/1433-187x-00308 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Matthys H., Heger M. (2007). Treatment of acute bronchitis with a liquid herbal drug preparation from Pelargonium sidoides (EPs 7630): A randomised, double-blind, placebo-controlled, multicentre study . Curr. Med. Res. Opin. 23 , 323–331. 10.1185/030079906X167318 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Matthys H., Lizogub V. G., Malek F. A., Kieser M. (2010). Efficacy and tolerability of EPs 7630 tablets in patients with acute bronchitis: A randomised, double-blind, placebo-controlled dose-finding study with a herbal drug preparation from Pelargonium sidoides . Curr. Med. Res. Opin. 26 , 1413–1422. 10.1185/03007991003798463 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Mazza M., Capuano A., Bria P., Mazza S. (2006). Ginkgo biloba and donepezil: A comparison in the treatment of alzheimer's dementia in a randomized placebo-controlled double-blind study . Eur. J. Neurol. 13 , 981–985. 10.1111/j.1468-1331.2006.01409.x [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Menon J., Thapa B. R., Kumari R., Puttaiah Kadyada S., Rana S., Lal S. B. (2023). Efficacy of oral psyllium in pediatric irritable bowel syndrome: A double-blind randomized control trial . J. Pediatr. Gastroenterol. Nutr. 76 , 14–19. 10.1097/MPG.0000000000003622 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Michael R., Bettina V., Eckehard L. (2022). Functional gastrointestinal disorders in children: Effectivity, safety, and tolerability of the herbal preparation STW-5 (Iberogast®) in general practice . Complement. Ther. Med. 71 , 102873. 10.1016/j.ctim.2022.102873 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Miotla P., Wawrysiuk S., Naber K., Markut-Miotla E., Skorupski P., Skorupska K., et al. (2018). Should we always use antibiotics after urodynamic studies in high-risk patients? Biomed. Res. Int. 2018 , 1607425. 10.1155/2018/1607425 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Momoeda M., Sasaki H., Tagashira E., Ogishima M., Takano Y., Ochiai K. (2014). Efficacy and safety of Vitex agnus-castus extract for treatment of premenstrual syndrome in Japanese patients: A prospective, open-label study . Adv. Ther. 31 , 362–373. 10.1007/s12325-014-0106-z [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Moreira D. D. L., Teixeira S. S., Monteiro M. H. D., De-Oliveira A. C. a. X., Paumgartten F. J. R. (2014). Traditional use and safety of herbal medicines1 . Rev. Bras. Farmacogn. 24 , 248–257. 10.1016/j.bjp.2014.03.006 [ CrossRef ] [ Google Scholar ]
• Moreno R. A., Teng C. T., Almeida K. M., Tavares Junior H. (2006). Hypericum perforatum versus fluoxetine in the treatment of mild to moderate depression: A randomized double-blind trial in a Brazilian sample . Braz J. Psychiatry 28 , 29–32. 10.1590/s1516-44462006000100007 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Naheed B., O'brien P. M. S., Uthman O. A., O'mahony F., Naheed B. (2013). Non-contraceptive oestrogen-containing preparations for controlling symptoms of premenstrual syndrome . Cochrane Database Syst. Rev. 3 , CD010503. 10.1002/14651858.CD010503.pub2 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Nappi R. E., Malavasi B., Brundu B., Facchinetti F. (2005). Efficacy of Cimicifuga racemosa on climacteric complaints: A randomized study versus low-dose transdermal estradiol . Gynecol. Endocrinol. 20 , 30–35. 10.1080/09513590400020922 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Napryeyenko O., Borzenko I., Grp G. N. S. (2007). Ginkgo biloba special extract in dementia with neuropsychiatric features - a randomised, placebo-controlled, double-blind clinical trial . Arzneimittelforschung-Drug Res. 57 , 4–11. 10.1055/s-0031-1296579 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Nasab N. M., Bahrammi M. A., Nikpour M. R., Rahim F., Naghibis S. N. (2012). Efficacy of rivastigmine in comparison to ginkgo for treating Alzheimer's dementia . J. Pak Med. Assoc. 62 , 677–680. [ PubMed ] [ Google Scholar ]
• Naser B., Lund B., Henneicke-Von Zepelin H. H., Köhler G., Lehmacher W., Scaglione F. (2005). A randomized, double-blind, placebo-controlled, clinical dose-response trial of an extract of Baptisia, Echinacea and Thuja for the treatment of patients with common cold . Phytomedicine 12 , 715–722. 10.1016/j.phymed.2005.03.002 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Nicolussi S., Drewe J., Butterweck V., Meyer Zu Schwabedissen H. E. (2020). Clinical relevance of St. John's wort drug interactions revisited . Br. J. Pharmacol. 177 , 1212–1226. 10.1111/bph.14936 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Oelke M., Berges R., Schlafke S., Burkart M. (2014). Fixed-dose combination PRO 160/120 of sabal and urtica extracts improves nocturia in men with LUTS suggestive of BPH: Re-evaluation of four controlled clinical studies . World J. Urol. 32 , 1149–1154. 10.1007/s00345-014-1338-x [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Omer B., Krebs S., Omer H., Noor T. O. (2007). Steroid-sparing effect of wormwood (Artemisia absinthium) in crohn's disease: A double-blind placebo-controlled study . Phytomedicine 14 , 87–95. 10.1016/j.phymed.2007.01.001 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Osmers R., Friede M., Liske E., Schnitker J., Freudenstein J., Henneicke-Von Zepelin H. H. (2005). Efficacy and safety of isopropanolic black cohosh extract for climacteric symptoms . Obstet. Gynecol. 105 , 1074–1083. 10.1097/01.AOG.0000158865.98070.89 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Palm J., Steiner I., Abramov-Sommariva D., Ammendola A., Mitzenheim S., Steindl H., et al. (2017). Assessment of efficacy and safety of the herbal medicinal product BNO 1016 in chronic rhinosinusitis . Rhinology 55 , 142–151. 10.4193/Rhin16.103 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Pares A., Planas R., Torres M., Caballeria J., Viver J. M., Acero D., et al. (1998). Effects of silymarin in alcoholic patients with cirrhosis of the liver: Results of a controlled, double-blind, randomized and multicenter trial . J. Hepatology 28 , 615–621. 10.1016/s0168-8278(98)80285-7 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Passali D., Loglisci M., Passali G. C., Cassano P., Rodriguez H. A., Bellussi L. M. (2015). A prospective open-label study to assess the efficacy and safety of a herbal medicinal product (Sinupret) in patients with acute rhinosinusitis . ORL J. Otorhinolaryngol. Relat. Spec. 77 , 27–32. 10.1159/000370123 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Perić A., Gaćeša D., Barać A., Sotirović J., Perić A. V. (2020). Herbal drug EPs 7630 versus Amoxicillin in patients with uncomplicated acute bacterial rhinosinusitis: A randomized, open-label study . Ann. otology, rhinology, laryngology 129 , 969–976. 10.1177/0003489420918266 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Philipp M., Kohnen R., Hiller K. O. (1999). Hypericum extract versus imipramine or placebo in patients with moderate depression: Randomised multicentre study of treatment for eight weeks . Br. Med. J. 319 , 1534–1538. 10.1136/bmj.319.7224.1534 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Randlov C., Mehlsen J., Thomsen C. F., Hedman C., Von Fircks H., Winther K. (2006). The efficacy of St. John's Wort in patients with minor depressive symptoms or dysthymia - a double-blind placebo-controlled study . Phytomedicine 13 , 215–221. 10.1016/j.phymed.2005.11.006 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Rapaport M. H., Nierenberg A. A., Howland R., Dording C., Schettler P. J., Mischoulon D. (2011). The treatment of minor depression with St. John's Wort or citalopram: Failure to show benefit over placebo . J. Psychiatric Res. 45 , 931–941. 10.1016/j.jpsychires.2011.05.001 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Rechberger E., Rechberger T., Wawrysiuk S., Miotla P., Kulik-Rechberger B., Kuszka A., et al. (2020). A randomized clinical trial to evaluate the effect of canephron N in comparison to ciprofloxacin in the prevention of postoperative lower urinary tract infections after midurethral sling surgery . J. Clin. Med. 9 , 3391. 10.3390/jcm9113391 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Rechberger E., Wrobel A., Kulik-Rechberger B., Miotla P., Rechberger T. (2022). Femistina versus Canephron as a prevention of urinary tract infections after midurethral sling surgery - non-inferiority study . Eur. J. Obstet. Gynecol. Reprod. Biol. 277 , 71–76. 10.1016/j.ejogrb.2022.08.009 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Rich G., Shah A., Koloski N., Funk P., Stracke B., Köhler S., et al. (2017). A randomized placebo-controlled trial on the effects of Menthacarin, a proprietary peppermint- and caraway-oil-preparation, on symptoms and quality of life in patients with functional dyspepsia . Neurogastroenterol. Motil. 29 , e13132. 10.1111/nmo.13132 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Rösch W., Vinson B., Sassin I. (2002). A randomised clinical trial comparing the efficacy of a herbal preparation STW 5 with the prokinetic drug cisapride in patients with Dysmotility type of functional dyspepsia . Z. für Gastroenterol. 40 , 401–408. 10.1055/s-2002-32130 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Rosien U. (2019). Iberogast® causes potentially life-threatening liver damages: Finally, warning notices are included in the use instructions by Bayer . Arzneiverordnung der Praxis 46 , 5–7. [ Google Scholar ]
• Sabadash M., Shulyak A. (2017). Canephron® N in the treatment of recurrent cystitis in women of child-bearing age: A randomised controlled study . Clin. Phytoscience 3 , 9. 10.1186/s40816-017-0046-7 [ CrossRef ] [ Google Scholar ]
• Saito Y. A., Rey E., Almazar-Elder A. E., Harmsen S. W., Zinsmeister A. R., Locke R. G., et al. (2010). A randomized, double-blind, placebo-controlled trial of St john's wort for treating irritable bowel syndrome . Am. J. Gastroenterology 105 , 170–177. 10.1038/ajg.2009.577 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Sarris J., Fava M., Schweitzer I., Mischoulon D. (2012). St john's wort ( Hypericum perforatum ) versus sertraline and placebo in major depressive disorder: Continuation data from a 26-week RCT . Pharmacopsychiatry 45 , 275–278. 10.1055/s-0032-1306348 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Saust L. T., Bjerrum L., Siersma V., Arpi M., Hansen M. P. (2018). Quality assessment in general practice: Diagnosis and antibiotic treatment of acute respiratory tract infections . Scand. J. Prim. Health Care 36 , 372–379. 10.1080/02813432.2018.1523996 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Schaefer A., Kehr M. S., Giannetti B. M., Bulitta M., Staiger C. (2016). A randomized, controlled, double-blind, multi-center trial to evaluate the efficacy and safety of a liquid containing ivy leaves dry extract (EA 575®) vs. placebo in the treatment of adults with acute cough . Die Pharm. 71 , 504–509. 10.1691/ph.2016.6712 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Schellenberg R. (2001). Treatment for the premenstrual syndrome with agnus castus fruit extract: Prospective, randomised, placebo controlled study . BMJ 322 , 134–137. 10.1136/bmj.322.7279.134 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Schellenberg R., Zimmermann C., Drewe J., Hoexter G., Zahner C. (2012). Dose-dependent efficacy of the Vitex agnus castus extract Ze 440 in patients suffering from premenstrual syndrome . Phytomedicine 19 , 1325–1331. 10.1016/j.phymed.2012.08.006 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Schloss J., Ryan K., Steel A. (2021). A randomised, double-blind, placebo-controlled clinical trial found that a novel herbal formula Urox® (Bedtime Buddy®) assisted children for the treatment of nocturnal enuresis . Phytomedicine 93 , 153783. 10.1016/j.phymed.2021.153783 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Schneider L. S., Dekosky S. T., Farlow M. R., Tariot P. N., Hoerr R., Kieser M. (2005). A randomized, double-blind, placebo-controlled trial of two doses of Ginkgo biloba extract in dementia of the Alzheimer's type . Curr. Alzheimer Res. 2 , 541–551. 10.2174/156720505774932287 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Scholz I., Liakoni E., Hammann F., Grafinger K. E., Duthaler U., Nagler M., et al. (2021). Effects of Hypericum perforatum (St John's wort) on the pharmacokinetics and pharmacodynamics of rivaroxaban in humans . Br. J. Clin. Pharmacol. 87 , 1466–1474. 10.1111/bcp.14553 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Seifritz E., Hatzinger M., Holsboer-Trachsler E. (2016). Efficacy of Hypericum extract WS(®) 5570 compared with paroxetine in patients with a moderate major depressive episode - a subgroup analysis . Int. J. Psychiatry Clin. Pract. 20 , 126–132. 10.1080/13651501.2016.1179765 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Seifritz E., Schlafke S., Holsboer-Trachsler E. (2019). Beneficial effects of Silexan on sleep are mediated by its anxiolytic effect . J. Psychiatr. Res. 115 , 69–74. 10.1016/j.jpsychires.2019.04.013 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Shelton R. C., Keller M. B., Gelenberg A., Dunner D. L., Hirschfeld R., Thase M. E., et al. (2001). Effectiveness of St john's wort in major depression: A randomized controlled trial . JAMA 285 , 1978–1986. 10.1001/jama.285.15.1978 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Singer A., Schmidt M., Hauke W., Stade K. (2011). Duration of response after treatment of mild to moderate depression with Hypericum extract STW 3-VI, citalopram and placebo: A reanalysis of data from a controlled clinical trial . Phytomedicine 18 , 739–742. 10.1016/j.phymed.2011.02.016 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Sommer H., Harrer G. (1994). Placebo-controlled double-blind study examining the effectiveness of an hypericum preparation in 105 mildly depressed patients . J. Geriatr. Psychiatry Neurol. 7 ( 1 ), S9–S11. 10.1177/089198879400700104 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Soyka M., Mann K. (2018). “ Medikamentenabhängigkeit ,” in Entstehungsbedingungen - klinik - therapie (Stuttgart: Schattauer; ). [ Google Scholar ]
• Stange R. (2014). Beliebtheit und Akzeptanz von Phytopharmaka bei Publikum und Verordnern . Z. fur Phytother. 35 , 16–20. 10.1055/s-0033-1349783 [ CrossRef ] [ Google Scholar ]
• Stange R., Schneider B., Albrecht U., Mueller V., Schnitker J., Michalsen A. (2017). Results of a randomized, prospective, double-dummy, double-blind trial to compare efficacy and safety of a herbal combination containing Tropaeoli majoris herba and Armoraciae rusticanae radix with co-trimoxazole in patients with acute and uncomplicated cystitis . Res. Rep. Urol. 9 , 43–50. 10.2147/RRU.S121203 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Stein D. J., Palk A. C., Kendler K. S. (2021). What is a mental disorder? An exemplar-focused approach . Psychol. Med. 51 , 894–901. 10.1017/S0033291721001185 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Storr M., Stracke B. (2022). Menthacarin for long-term treatment of functional dyspepsia – results from a clinical trial follow-up . Z. für Gastroenterol. 61 , 257–267. 10.1055/a-1823-1333 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Szegedi A., Kohnen R., Dienel A., Kieser M. (2005). Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St john's wort): Randomised controlled double blind non-inferiority trial versus paroxetine . BMJ 330 , 503. 10.1136/bmj.38356.655266.82 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Tanamly M. D., Tadros F., Labeeb S., Makld H., Shehata M., Mikhail N., et al. (2004). Randomised double-blinded trial evaluating silymarin for chronic hepatitis C in an Egyptian village: Study description and 12-month results . Dig. Liver Dis. 36 , 752–759. 10.1016/j.dld.2004.06.015 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Tanner M., Karen Roddis J. (2018). Antibiotics for acute bronchitis . Nurs. Stand 32 , 41–43. 10.7748/ns.2018.e11123 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Tanwar S., Trembling P. M., Hogan B. J., Srivastava A., Parkes J., Harris S., et al. (2017). Noninvasive markers of liver fibrosis: On-treatment changes of serum markers predict the outcome of antifibrotic therapy . Eur. J. Gastroenterology Hepatology 29 , 289–296. 10.1097/MEG.0000000000000789 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Timmer A., Günther J., Motschall E., Rücker G., Antes G., Kern W. V. (2013). Pelargonium sidoides extract for treating acute respiratory tract infections . Cochrane Database Syst. Rev. , CD006323. 10.1002/14651858.CD006323.pub3 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Uebelhack R., Gruenwald J., Graubaum H. J., Busch R. (2004). Efficacy and tolerability of Hypericum extract STW 3-VI in patients with moderate depression: A double-blind, randomized, placebo-controlled clinical trial . Adv. Ther. 21 , 265–275. 10.1007/BF02850158 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Van Dongen M., Van Rossum E., Kessels A., Sielhorst H., Knipschild P. (2003). Ginkgo for elderly people with dementia and age-associated memory impairment: A randomized clinical trial . J. Clin. Epidemiol. 56 , 367–376. 10.1016/s0895-4356(03)00003-9 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Van Gurp G., Meterissian G. B., Haiek L. N., Mccusker J., Bellavance F. (2002). St john's wort or sertraline? Randomized controlled trial in primary care . Can. Fam. Physician 48 , 905–912. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Verlaet A. A., Ceulemans B., Verhelst H., Van West D., De Bruyne T., Pieters L., et al. (2017). Effect of Pycnogenol® on attention-deficit hyperactivity disorder (ADHD): Study protocol for a randomised controlled trial . Trials 18 , 145. 10.1186/s13063-017-1879-6 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Vermes G., Banhidy F., Acs N. (2005). The effects of remifemin on subjective symptoms of menopause . Adv. Ther. 22 , 148–154. 10.1007/BF02849885 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Voican C. S., Corruble E., Naveau S., Perlemuter G. (2014). Antidepressant-Induced liver injury: A review for clinicians . Am. J. Psychiatry 171 , 404–415. 10.1176/appi.ajp.2013.13050709 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Von Arnim U., Peitz U., Vinson B., Gundermann K. J., Malfertheiner P. (2007). STW 5, a phytopharmacon for patients with functional dyspepsia: Results of a multicenter, placebo-controlled double-blind study . Am. J. Gastroenterol. 102 , 1268–1275. 10.1111/j.1572-0241.2006.01183.x [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Vorbach E. U., Arnoldt K. H., Hubner W. D. (1997). Efficacy and tolerability of St. John's Wort extract LI 160 versus imipramine in patients with severe depressive episodes according to ICD-10 . Pharmacopsychiatry 30 , 81–85. 10.1055/s-2007-979524 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Vorbach E. U., Hubner W. D., Arnoldt K. H. (1994). Effectiveness and tolerance of the hypericum extract LI 160 in comparison with imipramine: Randomized double-blind study with 135 outpatients . J. Geriatr. Psychiatry Neurol. 7 ( 1 ), S19–S23. 10.1177/089198879400700107 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Wachtel-Galor S., Benzie I. F. F. (2011). “ Herbal medicine: An introduction to its history, usage, regulation, current trends, and research needs ,” in Herbal medicine: Biomolecular and clinical aspects . Editors Benzie I. F. F, Wachtel-Galor S. 2nd ed (Boca Raton, FL: CRC Press; ). [ PubMed ] [ Google Scholar ]
• Wagenlehner F. M., Abramov-Sommariva D., Holler M., Steindl H., Naber K. G. (2018). Non-antibiotic herbal therapy (BNO 1045) versus antibiotic therapy (fosfomycin trometamol) for the treatment of acute lower uncomplicated urinary tract infections in women: A double-blind, parallel-group, randomized, multicentre, non-inferiority phase III trial . Urol. Int. 101 , 327–336. 10.1159/000493368 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Wawrysiuk S., Rechberger T., Kubik-Komar A., Kolodynska A., Naber K., Miotla P. (2022). Postoperative prevention of urinary tract infections in patients after urogynecological surgeries-nonantibiotic herbal (canephron) versus antibiotic prophylaxis (fosfomycin trometamol): A parallel-group, randomized, noninferiority experimental trial . Pathogens 12 , 27. 10.3390/pathogens12010027 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Wheatley D. (1997). LI 160, an extract of St. John's Wort, versus amitriptyline in mildly to moderately depressed outpatients - a controlled 6-week clinical trial . Pharmacopsychiatry 30 , 77–80. 10.1055/s-2007-979523 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Woelk H. (2000). Comparison of St john's wort and imipramine for treating depression: Randomised controlled trial . BMJ 321 , 536–539. 10.1136/bmj.321.7260.536 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Woelk H., Schlafke S. (2010). A multi-center, double-blind, randomised study of the Lavender oil preparation Silexan in comparison to Lorazepam for generalized anxiety disorder . Phytomedicine 17 , 94–99. 10.1016/j.phymed.2009.10.006 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Wortelboer U., Cohrs S., Rodenbeck A., Rüther E. (2002). Tolerability of hypnosedatives in older patients . Drugs and Aging 19 , 529–539. 10.2165/00002512-200219070-00006 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Wuttke W., Seidlova-Wuttke D., Gorkow C. (2003). The Cimicifuga preparation BNO 1055 vs. Conjugated estrogens in a double-blind placebo-controlled study: effects on menopause symptoms and bone markers . Maturitas 44 , S67–S77. 10.1016/s0378-5122(02)00350-x [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Yuan H., Ma Q., Ye L., Piao G. (2016). The traditional medicine and modern medicine from natural products . Molecules 21 , 559. 10.3390/molecules21050559 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Yuan J., He Q., Nguyen L. H., Wong M. C. S., Huang J., Yu Y., et al. (2021). Regular use of proton pump inhibitors and risk of type 2 diabetes: Results from three prospective cohort studies . Gut 70 , 1070–1077. 10.1136/gutjnl-2020-322557 [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Zavala-Cerna M. G., Segura-Cobos M., Gonzalez R., Zavala-Trujillo I. G., Navarro-Perez S. F., Rueda-Cruz J. A., et al. (2020). The clinical significance of high antimicrobial resistance in community-acquired urinary tract infections . Can. J. Infect. Dis. Med. Microbiol. 2020 , 2967260–2967267. 10.1155/2020/2967260 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
• Ziegler G., Ploch M., Miettinen-Baumann A., Collet W. (2002). Efficacy and tolerability of valerian extract LI 156 compared with oxazepam in the treatment of non-organic insomnia-a randomized, double-blind, comparative clinical study . Eur. J. Med. Res. 7 , 480–486. [ PubMed ] [ Google Scholar ]
• Zielińska S., Jezierska-Domaradzka A., Wójciak-Kosior M., Sowa I., Junka A., Matkowski A. M. (2018). Greater celandine's ups and Downs−21 centuries of medicinal uses of chelidonium majus from the viewpoint of today's Pharmacology . Front. Pharmacol. 9 , 299. 10.3389/fphar.2018.00299 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]

• Share full article

Advertisement

Supported by

Guest Essay

To Save Life on Earth, Bring Back Taxonomy

By Robert Langellier

Mr. Langellier is a writer and field botanist in Vermont.

In 2009, the botanist Naomi Fraga was hunting a flower without a name near Carson City, Nev. Ms. Fraga saw that the plant was going extinct in real time as its desert valley habitat was bulldozed to make way for Walmarts and housing developments. But in order to seek legal protections for it, she had to give it a name.

The diminutive yellow flower became the Carson Valley monkeyflower or, officially, Erythranthe carsonensis, allowing conservationists to petition the U.S. Fish and Wildlife Service to safeguard it under the Endangered Species Act. If their petition is approved, the flower will go from unknown to critically important in less than a generation, at least as far as Western science is concerned.

Taxonomy, the science of naming and classifying organisms, is the foundation for conserving disappearing plants and animals. Yet the field — often viewed as an archaic, dusty tradition that harks back to intrepid 19th-century botanists describing the plants of newly colonized lands — is dying. Several decades after the taxonomic frenzy of 1830 to 1920, when Western scientists went deep into far-flung regions of the world, molecular genetics revolutionized our ability to classify species, and began vacuuming up funding while the analog field of taxonomy was left to languish.

With genetic sequences, we can now identify the fundamental building blocks of life, but we need to be able to interpret genetic data in a way that humans can understand and use. That’s taxonomy’s job. And if we want to save what’s left of the vast diversity of life on Earth, we’ll have to reinvest in this science. How we delineate between species determines what we choose to save.

The dire state of taxonomy in the United States might be best illustrated by the Flora of North America, the definitive 30-volume attempt to name and describe every plant species here and in Canada. The project began in the 1980s, but it still hasn’t been completed because its contributors have struggled to secure consistent funding. By the time the last volume is completed in 2026, it will have to be revised immediately. For instance, its first volume, on ferns, released in 1993, is utterly out of date as new species have been discovered and nonnative species have moved in. Imagine trying to understand a 2024 Camry with a manual from 1993. That’s what botanists and conservationists trying to maintain biodiversity are working with.

The Flora of North America has been the victim of a broad shift in our scientific priorities as a nation. The National Science Foundation is the main funder of American botany. But since the 1980s and 1990s, its funding has increasingly gone to hypothesis-driven, laboratory-based research. When the Flora’s contributors ask university botanists to work on the project, it often must be done pro bono.

We are having trouble retrieving the article content.

Please enable JavaScript in your browser settings.

Thank you for your patience while we verify access. If you are in Reader mode please exit and  log into  your Times account, or  subscribe  for all of The Times.

Thank you for your patience while we verify access.

Already a subscriber?  Log in .

Want all of The Times?  Subscribe .

REVIEW article

Research progress of treating hyperuricemia in rats and mice with traditional chinese medicine.

• 1 Key Laboratory of Basic and Application Research of Beiyao, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin, China
• 2 School of Life Sciences, Guangzhou University, Guangzhou, China

Hyperuricemia (HUA) is a common chronic metabolic disease caused by abnormal purine metabolism and uric acid excretion. Despite extensive research on HUA, no clear treatment has been found so far. Improving purine metabolism and promoting uric acid excretion is crucial for the effective treatment of HUA. In recent years, traditional Chinese medicine and traditional Chinese medicine prescriptions have shown good effects in treating HUA. This article summarizes the latest progress in treating HUA in rats and mice using traditional Chinese medicine and prescriptions, elaborates on the pathogenesis of HUA, explores the application of commonly used traditional Chinese medicine treatment methods and prescriptions, and discusses the previous pharmacological mechanisms. In general, our research indicates that traditional Chinese medicine can effectively relieve the symptoms related to elevated uric acid levels in HUA rats and mice. However, further exploration and research are needed to verify its efficacy, safety, and feasibility.

1 Introduction

Hyperuricemia is a prevalent chronic metabolic disorder resulting from impaired purine metabolism and inadequate uric acid excretion ( Wang et al., 2022 ). The process of uric acid production and excretion is shown specifically in Figure 1 . In males, HUA is generally diagnosed when the serum uric acid concentration exceeds 420 μmol/L, while in females, the threshold is set at 360 μmol/L ( Johnson et al., 2018 ). The global prevalence of HUA has increased due to improvements in living standards and dietary patterns. A nationally representative cross-sectional survey conducted during 2018–2019 estimated that approximately 14% of Chinese adults were affected by HUA ( Zhang et al., 2022 ). HUA can contribute to the development of gout, kidney disease, type 2 diabetes mellitus, as well as cardiovascular and cerebrovascular disorders, and Intestinal disorders, significantly impacting individuals’ overall wellbeing and health status ( Yanai et al., 2021 ).

Figure 1 . Uric acid production and excretion pathway. Uric acid is synthesized in the liver via the enzymatic action of xanthine oxidase and subsequently eliminated from the body through both renal.

At present, lifestyle improvement and drug therapy are the main means to control uric acid levels. Studies have confirmed that quitting smoking and drinking, a low-purine diet, and reducing the intake of greasy and high-fat foods can effectively reduce hyperuricemia ( Morgan and Singh, 2021 ). Extensive research has been conducted on this disease and some drugs, such as benzbromarone, sulfinpyrazone, and propoxur have been utilized in its treatment ( Strilchuk et al., 2019 ). Although these drugs demonstrate positive effects in reducing uric acid levels, prolonged usage can lead to adverse effects including skin rashes, liver damage, and potentially severe kidney complications ( Bose et al., 2014 ; Yang et al., 2022 ). Therefore, there is a need to develop medicines or natural medicinal ingredients that are safer and more effective.

Compared with traditional drugs for the treatment of high uric acid, the development of herbal extracts (e.g., aqueous extracts, alcoholic extracts, and active metabolites), which are characterized by multi-links, multi-levels, multi-targets, and low toxicity and side-effects, has become a new idea for the development of uric acid-reducing drugs. In recent years, more and more studies have been devoted to the mining of natural substances with uric acid-reducing activity from herbs. Studies have shown that plant metabolites, such as flavonoids, saponins, polysaccharides, and polyphenols, regulate uric acid metabolism by inhibiting the activity of key enzymes of uric acid synthesis and regulating various pathways such as uric acid transporter proteins, thus preventing or treating hyperuricemia and its complications. For example, both the aqueous and alcoholic extracts of Agrocybe aegerita were able to exhibit inhibitory effects on hepatic xanthine oxidase (XOD) activity and elevate renal organic anion transporter protein 1 (OAT1) in hyperuricemic mice ( Yong et al., 2018 ). Er Ding Granules (EDG) have been shown to effectively lower uric acid levels by down-regulating glucose transporter protein 9 (GLUT9) and urate anion transporter protein 1 (URAT1), while up-regulating organic anion transporter 1 (OAT1). These actions enhance uric acid excretion and reduce its production, providing a balanced and sustained therapeutic effect. EDG’s multi-target approach offers potential advantages over traditional urate-lowering drugs such as allopurinol and febuxostat, potentially leading to fewer side effects in the management of hyperuricemia ( Zhang W. et al., 2019 ). Compared to conventional methods, traditional Chinese medicine (TCM) offers several advantages in the treatment of hyperuricemia (HUA). One major advantage is TCM’s multi-target, multi-component approach, which can simultaneously address various pathways of uric acid metabolism. This comprehensive approach not only helps reduce serum uric acid levels but also alleviates related complications such as gout, hypertension, diabetes, and chronic kidney disease, contributing to overall health ( Yang et al., 2022 ). To summarize, this paper collects various related literature published in recent years from PubMed, Web of Science, CNKI, and other electronic databases with “hyperuricemia, traditional Chinese medicine, botanical medicine, drug metabolite, traditional Chinese medicine compound” as the main keywords, to provide a theoretical basis for the research and development of uric acid-lowering drugs. To provide a theoretical basis for the research and development of uric acid-lowering drugs. All botanical drugs’ names have been checked with Plants of the Word Online ( http://www.plantsoftheworldonline.org ).

2 Pathogenesis of hyperuricemia

The pathogenesis of hyperuricemia is complex. A growing body of research now suggests that the pathogenesis of hyperuricemia may be related to enzyme activity, uric acid transporter proteins, intestinal flora dysbiosis, and oxidative stress and inflammatory responses.

2.1 Dysregulation of enzyme activity

Uric acid synthesis involves a variety of enzymes, including xanthine XOD as the key enzyme in the body of uric acid production, purine nucleoside phosphorylase PNP catalyzed creatinine catabolism to produce hypoxanthine to further catalyze the oxidation of intermediate products xanthine, and ultimately xanthine oxidation into uric acid. When XOD activity is dysregulated, the higher activity of XOD will accelerate the catalytic oxidation of hypoxanthine and xanthine, resulting in a continuous increase in uric acid levels and hyperuricemia ( Chen et al., 2023 ). XOD catalyzes the oxidation and hydroxylation of hypoxanthine and xanthine to uric acid, generating reactive oxygen species such as superoxide anion and hydrogen peroxide at the flavin center. Elevated levels of these reactive oxygen species can lead to oxidative stress and ischemia-reperfusion injury. This oxidative stress can contribute to conditions such as hyperuricemia and metabolic syndrome ( Borges et al., 2002 ).

2.2 Imbalanced expression of uric acid transporter protein

Uric acid in the body is mainly excreted through the kidneys (about 2/3), and a small portion is excreted through the intestines (about 1/3), the uric acid transporter protein in the kidneys is the regulation of the dynamic balance of uric acid reabsorption and excretion, and plays an important role in the process of uric acid excretion ( Maiuolo et al., 2016 ). Uric acid transporter proteins are mainly classified into two groups, one is reabsorption transporter proteins, mainly including urate anion transporter protein 1 (URAT1), organic anion transporter protein 4 (OAT4) and glucose transporter protein 9 (GLUT9); the other is secretion-associated transporter proteins, mainly including organic anion transporters 1 and 3 (OAT1 and OAT3), multidrug resistance protein 4 (MRP4/ABCC4) and ATP-binding cassette subfamily G member 2 (ABCG2). Over-expression of uric acid reabsorption transporter proteins leads to abnormal uric acid reabsorption, resulting in elevated serum uric acid levels; under-expression of uric acid secretion transporter proteins causes a decrease in renal uric acid secretion and insufficient excretion results in elevated serum uric acid levels. The literature has reported that 90% of patients with hyperuricemia have an imbalance between renal excretion and expression of uric acid transporter protein ( Russo et al., 2022 ).

2.3 Oxidative stress and inflammatory response

Uric acid production is accompanied by XOD, which promotes the activation of reduced coenzyme Ⅱ and the release of reactive oxygen species. When uric acid levels are higher than normal physiological levels, oxidative stress damage to the body is amplified ( Kurajoh et al., 2021 ). Oxidative stress in vivo can activate related inflammatory factors and inflammatory pathways and induce innate immune responses, while the activation of related pro-inflammatory factors can induce inflammation. It has been reported that the development of hyperuricemia is closely related to oxidative stress and inflammatory responses ( Liu et al., 2021 ).

2.4 Imbalance of intestinal homeostasis

Transporter proteins that promote uric acid excretion are also present in the gut, and these transporter proteins are involved in the metabolic processes of gut microorganisms ( Hosomi et al., 2012 ). ABCG2, which is distributed in different parts of the small and large intestine, is a major uric acid secretion transporter protein that dominates intestinal uric acid excretion and regulates blood uric acid levels. Studies have shown that increased expression of ABCG2 was found in the intestine of denervated rats with impaired renal excretion, suggesting that increased expression of this transporter protein may be the key to intestinal excretion of uric acid ( Bhatnagar et al., 2016 ). In addition, chronic inflammation is a typical pathological feature of hyperuricemia ( Zhou et al., 2018 ). Intestinal flora may ameliorate hyperuricemia by repairing the intestinal mucosal barrier and attenuating the inflammatory response. Elevated levels of inflammatory factors negatively affect both epithelial integrity of the gut and gut flora homeostasis ( Luissint et al., 2016 ). Dysbiosis of the intestinal flora increases intestinal permeability and promotes translocation of bacteria or bacterial products such as lipopolysaccharide (LPS) ( Xu et al., 2019 ). Elevated serum LPS levels induce chronic inflammation and increase the risk of developing hyperuricemia. In addition, LPS is a metabolite of intestinal flora, and abnormal levels of LPS in the circulation are usually accompanied by an increase in the activity of XOD, an important enzyme in the oxidative metabolism of purines. Thus, dysbiosis of the intestinal flora and impaired intestinal barrier repair can lead to elevated levels of LPS in the circulation, causing chronic inflammation, which is a new factor in the pathogenesis of hyperuricemia.

3 Uric acid-lowering effects of botanical drugs extracts, active metabolites, and herbal formulas in hyperuricemic rats and mice

In recent years pharmacological studies have validated the therapeutic effects of several botanical drug extracts, active metabolites, and herbal formulas by establishing hyperuricemic animals. The respective uric acid-lowering effects and the potential mechanisms of action are summarized in Tables 1 – 3 , respectively. The chemical structures of the metabolites described in the paper are shown in Figure 2 .

Table 1 . Mechanism of action of botanical drugs extracts in preventing HUA.

Table 2 . Mechanism of action of botanical drugs active metabolites in preventing HUA.

Table 3 . Mechanism of Traditional Chinese medicine formulas in preventing HUA.

Figure 2 . The chemical structures of the metabolites involved in the thesis. Among them, (1) Rhubarbic Acid (Molecular formula: C 15 H 8 O 6 ), (2) Emodin (Molecular formula: C 15 H 10 O 5 ), (3) Berberine (Molecular formula: C 20 H 18 NO 4 + ), (4) Astilbin (Molecular formula: C 21 H 22 O 11 ), (5) Apigenin (Molecular formula: C 15 H 10 O 5 ), (6) Nuciferine (Molecular formula: C 19 H 21 NO 2 ), (7) Curcumin (Molecular formula: C 21 H 20 O 6 ), (8) Epigallocatechin-3-gallate (Molecular formula: C 22 H 18 O 11 ), (9) Resveratrol (Molecular formula: C 14 H 12 O 3 ), (10) Luteolin (Molecular formula: C 15 H 10 O 6 ), (11) Luteolin-4′-O-glucoside (Molecular formula: C 21 H 20 O 11 ), (12) Baicalein (Molecular formula: C 15 H 10 O 5 ).

3.1 Single botanical drug extracts

3.1.1 astragalus membranaceus bunge [fabaceae; astragali radix].

Astragalus membranaceus Bunge is a medicinal plant rich in flavonoids, saponins, polysaccharides, and triterpenoids, and exhibits diverse biological activities. Modern pharmacological studies have demonstrated its anti-inflammatory, antioxidant, and immunomodulatory effects ( Durazzo et al., 2021 ). Moreover, astragalus exerts renoprotective effects and regulates intestinal flora ( Shahzad et al., 2016 ). In a yeast- and potassium oxybate-induced hyperuricemic mouse model (HUA mice), fermented astragalus (BFA) effectively reduced blood urea nitrogen (BUN) and serum creatinine (SCr) levels while improving renal morphology. BFA upregulated renal ABCG2 protein expression to enhance uric acid excretion and downregulated renal URAT1 and GLUT9 expression to inhibit uric acid reabsorption. Additionally, BFA attenuated the renal inflammatory response by preserving the integrity of the intestinal mucosal barrier and reducing lipopolysaccharide-binding protein production. Metabolomic analysis revealed that BFA ameliorated HUA by suppressing boswellic acid production while enhancing the abundance of beneficial monocytic butyric acid bacteria, visceral odoriferous bacteria, Tanaka bacteria as well as fatty acid biosynthesis to maintain urea cycle homeostasis ( Wang et al., 2023 ).

3.1.2 Atractylodes macrocephala Koidz. [Asteraceae; Atractylodis rhizome]

Dried rhizomes of Atractylodes macrocephala Koidz. is commonly employed in traditional medicine for the treatment of gout due to its diuretic and anti-dampness properties ( Zhang et al., 2021 ). In a HUA rat model established by combining otacid potassium with yeast powder solubilization, it was observed that C. diff effectively reduced serum levels of uric acid (UA), adenosine deaminase (ADA), and XOD in hypouricemic rats. Hematoxylin-eosin staining revealed that Atractylodis macrocephalae rhizome improved renal tubular dilatation and interstitial inflammatory cell infiltration in hypouricemic rats. Furthermore, Atractylodis macrocephalae rhizome exhibited anti-inflammatory activity by downregulating macrophage interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels, activating the Adenosine 5′-monophosphate-activated protein kinase/Silent mating type information regulation 2 homolog-1 (AMPK/SIRT1) signaling pathway, inhibiting nuclear factor kappa-B (NF-κB) activation, and suppressing macrophage polarization towards a pro-inflammatory phenotype ( Qian et al., 2023 ).

3.1.3 Cichorium glandulosum Boiss. & A. Huet [Asteraceae; Cichorii herba cichorii radix]

Cichorii herba cichorii radix is the dried above-ground part or root of Cichorium glandulosum Boiss. et Huet or Cichorrium intybus, belonging to the Asteraceae family. Recent pharmacological studies have demonstrated Cichorii herba cichorii radix’s potent anti-inflammatory, antioxidant, hypoglycemic, hypolipidemic, and intestinal flora regulating effects ( Azay-Milhau et al., 2013 ; Chen et al., 2017 ; Boghrati et al., 2021 ). Bian M et al. discovered that chicory effectively reduces serum uric acid levels by inhibiting xanthine oxidase activity and upregulating expression of the uric acid transporter ABCG2 in the intestine ( Bian et al., 2018 ). To further investigate the potential relationship between chicory treatment and regulation of intestinal flora in HUA, Bian M induced HUA in quails using a high purine diet based on previous research findings. The study revealed that chicory intervention significantly decreased serum uric acid levels while increasing fecal uric acid levels, promoting repair of intestinal mucosal damage and improving intestinal barrier permeability. Moreover, analysis through 16S rRNA sequencing indicated that chicory restored gut microbiota balance by enhancing probiotic flora (Bifidobacterium, Salmonella family) and reducing pathogenic flora (Pylori family). This restoration was accompanied by downregulation of serum lipopolysaccharide (LPS) levels as well as renal Toll-like receptor 4/nuclear factor-kappa B inflammatory pathways, ultimately facilitating renal excretion of uric acid via attenuation of the LPS/Toll-like receptor 4 axis-mediated inflammatory response ( Bian et al., 2020 ).

3.1.4 Plantago asiatica L. [Plantaginaceae; Plantaginis Semen]

Plantaginis Semen is the dried mature seeds of Plantago asiatica L. or Plantago depressa Willd. a herb commonly employed for uric acid reduction ( Zeng et al., 2018 ; Sun et al., 2019 ). The phosphoinositide 3-kinase/Protein kinase B (PI3K/Akt) signaling pathway, an inflammatory pathway implicated in severe kidney injury and indirect modulation of uric acid excretion, can be inhibited by Plantago to ameliorate nephropathy and enhance uric acid excretion ( Dragos et al., 2020 ; Santos et al., 2020 ; Zhao et al., 2020 ). Furthermore, hyperuricemia has been associated with lipid metabolism ( Guo et al., 2020 ), but it remains unknown whether lipid metabolism plays a role in the therapeutic effects of Plantago on hyperuricemia treatment. Previous studies have shown that Plantago extract improves lipid accumulation in high-fat diet-induced obese mice ( Yang et al., 2017 ), while another study demonstrated that Plantago accelerates lipolysis through regulation of lipid metabolism disorders in a mouse model of hyperuricemia induced by potassium oxybate gavage; additionally, anti-hyperuricemic effects were observed through downregulation of URAT1 expression and inhibition of the PI3K/Akt inflammatory pathway ( Yang et al., 2021 ).

3.1.5 Polygonum cuspidatum Siebold & Zucc. [Polygonaceae; Polygoni cuspidate rhizome et radix]

The Polygoni cuspidate rhizome et radix is derived from the dried rhizomes and roots of Polygonum cuspidatum Sieb.et Zucc, a perennial herb of the Polygonicuspidate family. PC has anti-inflammatory, antibacterial, antiviral, antioxidant, hypoglycemic and anti-hyperuric acid pharmacological activities ( Ammar et al., 2022 ; Bian et al., 2022 ; Lin et al., 2022 ). Metabolomics is an emerging discipline in the 20th century and is of great importance in elucidating the mechanisms of pharmacological effects of Chinese medicines ( Wu et al., 2019 ). Recent reports have found that polydatin can improve and treat HUA through amino acid metabolism, lipid metabolism and energy metabolism ( Ge et al., 2023 ). Ma et al. found that PC could upregulate the expression of Adenosine 5′-monophosphate-activated protein kinase (AMPK) and its downstream molecule FOXO3α, and inhibit the bioactivity of Toll-likereceptor4 (TLR4), NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and Monocyte Chemoattractant Protein-1 (MCP-1), key signaling molecules of the immune inflammatory network pathway to improve HUA-mediated immunoinflammatory metabolic kidney damage ( Liu et al., 2005 ; Ma et al., 2019 ). Hu et al. isolated two active compounds from PC: 1-(4-hydroxy-2-methoxyphenyl)-2-(4-hydroxy-3,5-dimethylphenyl) butane-1,2,3-triol and 1-(4-hydroxy-2-methoxyphenyl)-2-(4-hydroxy-3,5-dimethylphenyl)-3-methylbutane-1,2-diol. In vitro and in vivo experiments have demonstrated the ability of both compounds to reduce UA levels and improve renal morphological and pathological changes through competitive inhibition of XOD activity. In addition, the mechanisms of anti-HUA are closely related to galactose metabolism, taurine and hypotaurine metabolism, purine metabolism and energy metabolism ( Hu et al., 2023 ).

3.1.6 Smilax china L. [Smilacaceae; Smilacis chinae rhizoma]

Smilacis chinae rhizoma, the dried rhizome of Smilax china L., a member of the lily family, possesses therapeutic properties including dampness relief, turbidity removal, wind and paralysis dispelling, as well as detoxification and blood stasis dispersion. It exhibits anti-inflammatory, antioxidant, anticancer, hypoglycemic, and diuretic activities ( Wang et al., 2013 ; Hooda et al., 2014 ; Bao et al., 2018 ; Xu et al., 2022b ). Chen investigated different fractions of sarsaparilla using petroleum ether, chloroform, ethyl acetate n-butanol and ethanol in HUA rats. The ethyl acetate fraction demonstrated significant uric acid-lowering effects. Caffeic acid, resveratrol rutin and oxidized resveratrol isolated from the ethyl acetate fraction exhibited in vitro inhibition of xanthine oxidase activity ( Chen et al., 2011b ). Wu previously reported that sarsaparilla saponin significantly reduced serum uric acid levels in a mouse model of HUA. Further investigation revealed that sarsaparilla saponin co-regulated renal URAT1 and GLUT9 expression in mice by upregulating OAT1 while inhibiting XOD ( Wu et al., 2015 ). Hong et al. (2014) employed Liquid Chromatograph Mass Spectrometer analysis combined with bioinformatics to identify differential proteins in kidney tissue from sarsaparilla-intervened HUA rats. Sarsaparilla was found to upregulate catalase expression for alleviating oxidative stress levels.

3.1.7 Morus alba L. [Moraceae; Mori ramulus]

Mori ramulus (MR) is a branch of the mulberry tree, extensively utilized in traditional medicine as an anti-rheumatic agent. MR contains various active constituents, including flavonoids, phenylpropanoids, and coumarins, exhibiting pharmacological activities such as antioxidative, anti-inflammatory, anti-hyperlipidemic, and anti-hyperglycemic effects ( Xiang et al., 2021 ). Shi et al. (2012) discovered that the alcoholic extract derived from Morus alba exhibited significant efficacy in reducing serum uric acid levels and increasing 24-hour urine uric acid excretion as well as partial uric acid excretion in mice with HUA. This extract effectively downregulated renal mURAT1 and mGLUT9 expression, while up-regulating the expression of mOAT1, thereby enhancing uric acid excretion. Furthermore, EMR treatment resulted in reduced serum creatinine and BUN levels, increased creatinine clearance, upregulated the expression of mOCT1/2, and facilitated HUA improvement.

3.1.8 Salvia plebeia R. Br. [Lamiaceae; Salviae herba]

Salvia plebeia R. Br. (SP) is a Labiatae herbaceous plant, widely distributed in China, Korea, Japan, India, Iran, and Australia. In China, it is commonly referred to as “lychee grass” and has been extensively used in traditional medicine for treating ascites swelling and nephritic edema. Numerous studies have documented the anti-inflammatory, antioxidant, antibacterial, and antiviral properties of SP ( Chen and Kang, 2014 ; Jin et al., 2015 ). Recent research focusing on xanthine oxidase inhibitors has revealed that SP exhibits potent inhibitory effects on XOD activity. Kim et al. demonstrated that baicalin and lignans present in SP significantly contribute to the inhibition of XOD activity with IC50 values below 5 μm ( Kim et al., 2017 ).

3.2 Single bioactive metabolites

3.2.1 rhubarbic acid/emodin.

Rhei radix et rhizome, a traditional Chinese medicine, is derived from the dried roots and rhizomes of Polygonum palmatum , Rheum palmatum , Rheum tanguticum , or Rheum officinale in the family Polygonaceae . Rhubarb contains anthraquinones such as rhubarbic acid, rhubarbol, and rhubarb phenol which possess antibacterial, anti-inflammatory, antiviral, antioxidant properties as well as exhibit effects against HUA and renal fibrosis ( Mueller-Heupt et al., 2022 ). Meng et al. (2023) demonstrated that Rhubarbic Acid has notable uric acid-lowering and nephroprotective effects on HUA mice by significantly reducing serum uric acid levels along with serum creatinine and blood urea nitrogen levels while inhibiting XOD activity in mouse liver. Emodin is an anthraquinone from rhubarb that has anti-inflammatory, detoxifying, and gut motility-promoting effects; in addition, some studies have reported that emodin can also inhibit XOD activity ( Shi et al., 2014 ). A recent study by Hou et al. (2023) found that rhodopsin can significantly reduce serum uric acid levels, promote uric acid excretion, and thus play a role in the treatment of hyperuricemia.

3.2.2 Berberine

Phellodendri chinense cortex (PC), commonly known as “Chuan Huang Bai,” is extensively utilized for the treatment of damp-heat diarrhoea, jaundice and dysentery, pyorrhoea, and astringent pain. PC has been traditionally employed as a medicinal remedy for gout and hyperuricemia, such as in Ermiao Wan, Sanmiao Wan, and Ventilation Soup. Pharmacological investigations have revealed that PC contains diverse bioactive constituents including alkaloids and flavonoids. Notably, berberine, an alkaloid group present in PC, has recently demonstrated anti-hyperuricemic activity by modulating the expression of URAT1 and GLUT9 transporter proteins along with XOR activity regulation ( Li et al., 2021 ; Naz et al., 2021 ). Xu et al. (2021) investigated the hypouricemic and nephroprotective effects of dihydroberberine in hyperuricemic mice and observed significant reduction in serum uric acid levels as well as XOD levels while inhibiting hepatic XOD activity and ADA activities. Furthermore, they found downregulation of renal XOD mRNA and protein expression.

3.2.3 Astilbin

Extracted from sarsaparilla rhizomes, Astilbin is an active flavonoid compound that is widely used in traditional Chinese medicine therapy for its anti-arthritic, anti-hepatic, and anti-kidney injury effects. Wang et al. (2016) , in order to study the effect of Astilbin on potassium oxybate-induced hyperuricemia mice and its mechanism of action. The results showed that Astilbin significantly reduced serum uric acid (Sur) levels, and its effects were associated with the inhibition of GLUT9 and URAT1, expression and the upregulation of ABCG2, OAT1/3 and OCT1 expression. In addition, Aastilbin inhibited the activation of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) cascade and overexpression of suppressor of cytokine signaling 3 (SOCS3), and exerted nephroprotective effects by inhibiting oxidative stress.

3.2.4 Apigenin

Apigenin (4,5,7 -trihydroxyflavone) is a naturally occurring flavonoid that is mainly derived from Apium graveolens L. (celery), but is also found in a wide variety of plants, fruits, and vegetables. There is growing evidence that apigenin attenuates UA in mice with chromosome- or potassium oxybate-induced HUA ( Chesworth et al., 2021 ). Previously, it has been shown that apigenin can reduce serum uric acid levels, decrease the levels of GLUT9 and URAT1 transport proteins, increase the levels of OAT1 transport proteins, and inhibit the JAK2/STAS3 signaling pathway in a mouse model of acute hyperuricemia induced by potassium oxybate and Hypoxanthine, thus exerting a therapeutic effect on hyperuricemia ( Liu et al., 2022 ).

3.3 Traditional Chinese medicine formulas

Throughout the millennia of Chinese culture, Chinese medicine has become an integral component of the comprehensive medical system (Xu et al., 2013). Chinese medicine formulas are not haphazardly concocted but have evolved over thousands of years through clinical practice. According to Chinese medicine, hyperuricemia primarily arises from dampness and heat, thus treatment predominantly focuses on clearing heat and alleviating dampness using formulations like Ermiao Wan, Er Ding Granules, and Qu Zhuo Tong Bi Tang. Our analysis of commonly employed traditional Chinese medicine prescriptions has revealed various approaches for managing hyperuricemia ( Table 3 ).

3.3.1 Pharmacological mechanism of Ermiao Pill and similar formulations in treating HUA

Ermiao Wan (EMW) is derived from Zhu Zhenheng’s “Danxi Xinfa” and is utilized for the treatment of damp-heat infiltration, damp-heat banding, and gonorrhea. The complete formula comprises two botanical drugs, namely, Phellodendri chinense cortex and Atractylois rhizoma. Subsequently, based on their remarkable efficacy in reducing uric acid levels, Sanmiao Wan (SMW) and Simiao Pill were developed by later medical practitioners to enhance therapeutic outcomes. Previous studies have demonstrated that Phellodendri chinense cortex, Atractylois rhizoma and Coicis semen possess diuretic properties with the ability to eliminate dampness. Additionally, hyssop has traditionally been recognized for its downward-moving effect and frequent usage as a menstruation-inducing herb ( Zhao et al., 2014 ). Huang et al. (2019) conducted an investigation into the comprehensive composition and mechanism of action of EMW in treating HUA, identifying 24 alkaloids, 46 volatile components, 15 organic acids, 4 terpenoids, 3 lactones, 3 glycosides along with other compounds within this formulation. Metabolomic analysis revealed that EMW exerts anti-HUA effects through the regulation of multiple metabolic pathways including glycerolipid metabolism amino acid metabolism prochlorogenic bile acid metabolism taurine and hypotaurine metabolism as well as purine metabolism. Several studies have elucidated the mechanism of action of EMW in ameliorating HUA from a metabolomics perspective. Following EMW intervention, there was a significant reduction in serum uric acid levels. Metabolomics analysis identified 11 biomarkers exhibiting a reversal trend. Pathway analysis revealed that EMW may exert therapeutic effects on HUA rats through pathways such as phenylalanine metabolism, glycerophospholipid metabolism, tryptophan metabolism, and lipid metabolism ( Shan et al., 2021 ; Gu et al., 2023 ). Hyperuricemia can contribute to the development of chronic kidney disease and cardiovascular disease. Guo et al. (2015) investigated the combined protective effects of Siwu Tang and EMW on HUA and renal injury and demonstrated that this combination significantly reduced serum levels of uric acid, creatinine, triglycerides, and urea nitrogen. The underlying mechanism may involve decreased renal xanthine oxidase activity and upregulation of OAT1 and OAT3 expression. Serum metabolomic analysis revealed that SMW could partially regulate purine metabolism, amino acid metabolism, and energy metabolism to reverse the pathological process associated with HUA ( Jiang et al., 2017 ). Simiao Wan is utilized as a herbal formulation for adjunctive therapy in gout. A study conducted by Cao et al. (2021) demonstrated that Simiao Wan exhibits potential in ameliorating MSU-induced gouty arthritis and inhibiting hyperuricemia, possibly through the activation of the PI3K/Akt signaling pathway to promote M2 polarization. Zhang et al. (2023) discovered that Simiao powder could attenuate HUA in mice by reducing the expression of URAT1, GULT9, NLRP3, Phospho-Janus Kinase-2/Janus Kinase-2 (P-JAK2/JAK2), and Phospho-signal transducer and activator of transcription-3/signal transducer and activator of transcription-3 (P-STAT3/STAT3) in renal tissues; this mechanism of action may be associated with the suppression of NLRP3 inflammasome and Janus Kinase-2/signal transducer and activator of transcription-3 (JAK2/STAT3) signaling pathway. In summary, EMW and its analogs exhibit therapeutic potential against HUA through four pathways: inhibition of renal XOD activity; upregulation of transporter proteins OAT1 and OAT3; regulation of purine metabolism and amino acid metabolism; modulation of the PI3K/Akt and JAK2/STAT3 signaling pathways.

3.3.2 Pharmacological mechanism of Er Ding granules in treating HUA

The composition of Er Ding Granules includes four botanical drugs, namely, Violae herba, Taraxaci herba, Lobeliae chinensis herba and Isatidis radix, all of which were initially documented in the Shen Nong Ben Cao Jing. It is well-documented that Violae herba, Lobeliae chinensis herba and Isatidis radix possess anti-inflammatory and antibacterial properties. Additionally, Dandelion exhibits diuretic effects by increasing renal urine excretion. Zuo et al. (2018) demonstrated that treatment with Er Ding Granules significantly reduced serum uric acid levels in mice while down-regulating URAT1 mRNA expression in the kidneys of hyperuricemic mice and enhancing OAT3 mRNA expression. Zhang et al. (2019) divided the complete formula into water extracts as well as 50% ethanol and 95% ethanol extracts to investigate their anti-hyperuricemic activity. The results revealed a significant dose-dependent effect on serum uric acid levels for the 50% ethanol extract. Mechanistic studies indicated that the anti-hyperuricemic effect of the 50% ethanol extract primarily involved downregulation of GLUT9 and URAT1 protein expression along with upregulation of OAT1 protein expression. Downregulation of reabsorption proteins GLUT9 and URAT1 along with upregulation of secretory proteins OAT1 and OAT3 represent key mechanisms underlying the therapeutic effects exerted by Er Ding Granules on hyperuricemia.

3.3.3 Pharmacological mechanism of Qu Zhuo Tong Bi Tang in treating HUA

The empirical formula Qu Zhuo Tong Bi Tang (QZTBD) demonstrates definite clinical efficacy in the treatment of HUA and gout, as it effectively enhances kidney function, improves blood circulation, and alleviates pain. This formula comprises Smilacis chinae rhizoma, Dioscoreae spongiosae rhizoma, Coicis semen, Curcumae longae rhizoma, Cortdalis rhizoma and Siegesbeckiae herba ( Wen et al., 2021 ). Chen et al. (2016) employed serum metabolomics to investigate the impact of QZTBD on serum urine and other metabolites in HUA-induced rats. Their findings confirm that QZTBD significantly reduces serum uric acid levels by regulating amino acid metabolism, purine metabolism, and energy metabolism mechanisms. Song et al. utilized a combined analysis of network pharmacology and intestinal flora to elucidate the mechanism of action underlying QZTBD’s therapeutic effects against HUA. The results demonstrate that QZTBD has the potential to enhance the abundance of Allobaculum and Candidatus sacchairmonas while rectifying abnormal amino acid patterns. Additionally, it repairs compromised intestinal barriers by restoring Th17/Treg cell balance through modulation of the PI3K-AKT-mTOR pathway; furthermore reducing inflammatory factors such as IL-1β, interleukin-6 (IL-6), TNF-α, and interleukin-17 (IL-17) levels (S et al., 2023). In summary, QZTBD exerts its therapeutic effects on HUA through regulation of amino acid metabolism, purine metabolism, and energy metabolism. Additionally, it restores intestinal barrier integrity, inhibits the PI3K-AKT signaling pathway.

3.3.4 Pharmacological mechanism of Fangji Huangqi Tang in treating of HUA

The prescription Fangji Huangqi Tang is derived from the synopsis of the Golden Chamber written by Zhang Zhongjing, and it primarily focuses on treating Feng Shui or rheumatic diseases. Composed of Stephaniae tetrandrae radix, Astragali radix, Glycyrrhizae radix et rhizoma and Atractylodeis macrocephalae rhizoma, this representative prescription aims to replenish qi and promote water balance. Previous studies have reported that Stephaniae tetrandrae radix and Astragali radix possess diuretic effects which can improve kidney function. Additionally, Atractylodeis macrocephalae rhizoma and Glycyrrhizae radix et rhizoma have been found to reduce serum uric acid levels while providing renal protection ( Aksoy et al., 2012 ; Wang et al., 2018 ; Wei et al., 2018 ). Recent research has demonstrated that Fangji Huangqi Tang significantly lowers serum uric acid and creatinine levels while inhibiting IL-1β in both serum and kidneys of Hua mice. Furthermore, it effectively reduces NF-kB protein expression. Analysis of renal uric acid-related transporters revealed that Fangji Huangqi Tang upregulates the protein expression levels of renal OAT1, OAT3, and ABCG2 ( Xing et al., 2020 ). When used individually as single botanical drug or combined together in Fangji Huangqi Tang formulae, Stephaniae tetrandrae radix, Astragali radix and Atractylodeis macrocephalae rhizoma, exhibit diuretic effects with enhanced efficacy when combined together ( Lin et al., 2015 ). Moreover, their combination significantly upregulates the expression of renal uric acid secretion proteins OAT1, OAT3, and ABCG2 while substantially reducing organismal uric acid levels.

3.3.5 Pharmacological mechanism of Shi Wei Ru Xiang powder in the treating of HUA

Shiwei Ruxiang powder, a traditional Tibetan medicine, is commonly utilized in traditional Chinese medicine for the treatment of HUA. In a study conducted by Li et al. (2022) , network pharmacology and experimental validation were employed to investigate the effects of SWS on HUA in mice. The findings demonstrated that SWS ameliorated HUA through modulation of pivotal signaling pathways encompassing MAPK, nuclear factor κB (NF-κB), and NOD-like receptor signaling pathways.

3.3.6 Pharmacological mechanism of Cheqianzi Tang in the treating of HUA

In the Song Dynasty’s “Shengji Zonglu,” the Cheqianzi Tang (CQD) was discovered to possess the following therapeutic properties: heat-clearing and detoxification, dampness-promoting and dehumidifying effects. It has demonstrated a positive curative impact on hyperuricemia. The composition of CQD comprises Plantaginis semen, Achyranthis bidentatae radix, Typhae pollen, and Mori cortex. Studies have reported that psyllium decoction can ameliorate hyperuricemia by activating ABCG2, which facilitates uric acid excretion, as well as inducing downregulation of inflammatory and apoptotic factors mediated by inflammasome NLRP3 (J et al., 2023).

4 Discussion

This article provides a comprehensive review of the botanical drugs commonly used for treating HUA in rat and mice models and presents research findings that demonstrate the efficacy of everal specific botanicals, bio-metabolites and herbal formulations in inhibiting hepatic XOD activity, modulating renal uric acid transport proteins, suppressing inflammatory response pathways, and regulating product metabolism.

Xanthine oxidase, an enzyme crucial in the pathogenesis of HUA and uric acid homeostasis, catalyzes the oxidation of hypoxanthine to xanthine and further to uric acid ( Sang et al., 2017 ). Among the aforementioned botanical drugs, Atractylodes macrocephala Koidz., Phellodendron chinense C. K. Schneid. , Polygonum cuspidatum Siebold & Zucc., Smilax china L., Rheum palmatum L. and Salvia plebeia R. Br. exhibit inhibitory effects on XOD activity. Renal transporter proteins associated with uric acid metabolism can be categorized into two groups: URAT1, OAT4, GLUT9 as urate reabsorption transporters; OAT1, OAT3, MRP4/ABCC4, and ABCG2 as urate excretion transporters. Altered expression and function of these transporter proteins are implicated in HUA development ( Zhao et al., 2022 ). In addition to Phellodendron chinense C.K.Schneid and Cichorium glandulosum Boiss. & A. Huet which inhibit hepatic XOD activity while modulating renal uric acid-related transporter proteins; Plantago asiatica L., Astragalus membranaceus Bunge and Morus alba L. also regulate serum uric acid levels by modulating renal uric acid-related transporter proteins. Severe HUA can lead to renal inflammation and gut microbial dysbiosis; hence targeting inflammatory response inhibition along with modulation of gut microbial populations may offer a novel approach for improving HUA management ( Zhao et al., 2022 ). Among the ten botanical drugs mentioned above, Astragalus membranaceus Bunge and Cichorium glandulosum Boiss. & A. Huet can enhance hyperuricemia (HUA) by augmenting probiotics such as Bifidobacterium and Bacillus tansy, thereby fortifying the intestinal mucosal barrier. Additionally, Cichorium glandulosum Boiss. & A. Huet exhibits inhibitory effects on the TLR4/NF-kB inflammatory signaling pathway to impede the progression of HUA-induced nephritis. Conversely, Atractylodes macrocephala Koidz., Plantago asiatica L. and Polygonum cuspidatum Siebold & Zucc. mitigate further advancement of HUA primarily through suppression of NF-kB and PI3K/Akt inflammatory signaling pathways along with NLRP3 inflammatory vesicles. In summary, Chinese medicine effectively addresses HUA via four principal mechanisms of action ( Figure 3 ).

Figure 3 . Mechanism of action of traditional Chinese medicine in the treatment of HUA. Atractylodes macrocephala Koidz., Phellodendron chinense C. K. Schneid., Smilax china L., Rheum palmatum L., Polygonum cuspidatum Siebold & Zucc., and Salvia plebeia R. Br. exhibit direct inhibitory effects on XOD activity for uric acid reduction. Atractylodes macrocephala Koidz., Polygonum cuspidatum Siebold & Zucc. and Plantago asiatica L. exert their hypouricemic effects by suppressing the TLR4/NF-kB signaling pathway and NLRP3 inflammasomes. Phellodendron chinense C.K.Schneid., Morus alba L., Plantago asiatica L., Smilax china L. and Cichorium glandulosum Boiss. & A. Huet reduce uric acid levels by downregulating reabsorption-associated proteins and upregulating excretion-associated proteins in the kidney. Astragalus membranaceus Bunge and Cichorium glandulosum Boiss. & A. Huet directly target uric acid excretory proteins in the intestine or demonstrate hypouricemic effects through regulation of intestinal flora and protection of the intestinal mucosal barrier.

Traditional Chinese medicine has multiple advantages in the treatment of hyperuricemia. Firstly, it employs a multi-pathway, multi-target treatment strategy, which effectively reduces uric acid levels and improves overall health. Chinese herbal medicine achieves therapeutic goals through various pathways such as regulating uric acid production, increasing uric acid excretion, and reducing uric acid absorption. This comprehensive action can provide more lasting and balanced therapeutic effects.

Secondly, Chinese herbal medicine is mostly derived from natural sources and has undergone extensive historical validation and clinical practice. These medicines often have fewer side effects because they are more compatible with the human body’s natural processes. In contrast, many conventional uric acid-lowering drugs may cause common side effects such as indigestion and headaches ( Wang et al., 2020 ).

In addition, Chinese herbal medicine is often used in complex formulations, which not only enhances efficacy but also reduces the potential toxicity of individual components. For example, Ge Gen Qin Lian Tang, a classic Chinese herbal formula, is widely used for treating hyperuricemia. It has been proven effective in lowering uric acid levels and is considered safe ( Wang et al., 2023 ).

This article summaries research on the potential and mechanisms of herbal medicine for the treatment of hyperuricemia. The studies focused on reducing XOD activity, regulating uric acid transporter proteins, influencing inflammatory signaling pathways, and regulating gut microbial homeostasis. Although the studies on regulating intestinal microbial balance and upstream regulators of uric acid transporter proteins still need to be deepened, traditional Chinese medicines show good prospects for application in rat and mouse models. Overall, the treatment of hyperuricemia with traditional Chinese medicines not only demonstrates significant advantages in reducing uric acid levels, but also improves overall health and reduces the risk of complications. Pharmacological studies, clinical evidence and historical applications support the safety and efficacy of TCM in the treatment of hyperuricemia.

Author contributions

HB: Writing–original draft. ZZ: Writing–original draft. MZ: Resources, Supervision, Writing–review and editing. YS: Resources, Supervision, Writing–review and editing. YW: Resources, Supervision, Writing–review and editing. BL: Resources, Supervision, Writing–review and editing. QW: Funding acquisition, Project administration, Writing–review and editing. HK: Funding acquisition, Project administration, Writing–review and editing.

The authors declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Chief Scientist of Qi-Huang Project of National Traditional Chinese Medicine Inheritance and Innovation “One Hundred Million” Talent Project [Grant Number: (2021) No. 7]. Qi-Huang Scholar of National Traditional Chinese Medicine Leading Talents Support Program [Grant Number: (2018) No. 284]. National Famous Old Traditional Chinese Medicine Experts Inheritance Studio Construction Program of National Administration of TCM [Grant Number: (2022) No. 75]. The Seventh Batch of National Famous Old Traditional Chinese Medicine Experts Experience Heritage Construction Program of National Administration of TCM [Grant Number: (2022) No. 76].

Acknowledgments

Figures were created by Figdraw ( www.figdraw.com ).

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Aksoy, N., Dogan, Y., Iriadam, M., Bitiren, M., Uzer, E., Ozgonul, A., et al. (2012). Protective and therapeutic effects of licorice in rats with acute tubular necrosis. J. Ren. Nutr. 22 (3), 336–343. doi:10.1053/j.jrn.2011.07.002

PubMed Abstract | CrossRef Full Text | Google Scholar

Ammar, H., Touihri, I., Kholif, A. E., M'Rabet, Y., Jaouadi, R., Chahine, M., et al. (2022). Chemical composition, antioxidant, and antimicrobial activities of leaves of ajuga iva. Molecules 27 (20), 7102. doi:10.3390/molecules27207102

Azay-Milhau, J., Ferrare, K., Leroy, J., Aubaterre, J., Tournier, M., Lajoix, A. D., et al. (2013). Antihyperglycemic effect of a natural chicoric acid extract of chicory ( Cichorium intybus L.): a comparative in vitro study with the effects of caffeic and ferulic acids. J. Ethnopharmacol. 150 (2), 755–760. doi:10.1016/j.jep.2013.09.046

Bao, Y., Li, H., Li, Y., Li, Y., Li, F., Zhang, F., et al. (2018). Therapeutic effects of Smilax glabra and Bolbostemma paniculatum on rheumatoid arthritis using a rat paw edema model. Biomed. Pharmacother. 108, 309–315. doi:10.1016/j.biopha.2018.09.004

Bhatnagar, V., Richard, E., Wu, W., Nievergelt, M., Lipkowitz, S., Jeff, J., et al. (2016). Analysis of ABCG2 and other urate transporters in uric acid homeostasis in chronic kidney disease: potential role of remote sensing and signaling. Clin. Kidney J. 9 (3), 444–453. doi:10.1093/ckj/sfw010

Bian, M., Lin, J., Wang, Y., Zhang, B., Li, G., and Wang, H. (2018). Bioinformatic and metabolomic analysis reveal intervention effects of chicory in a quail model of hyperuricemia. Evidence-Based Complementary Altern. Med. 2018, 5730385. doi:10.1155/2018/5730385

Bian, M., Wang, J., Wang, Y., Nie, Z., Zhu, S., Sun, X., et al. (2020). Chicory ameliorates hyperuricemia via modulating gut microbiota and alleviating LPS/TLR4 axis in quail. Biomed. Pharmacother. 131, 110719. doi:10.1016/j.biopha.2020.110719

Bian, T., Xiao, L., Liang, L., Xie, P., Wang, L., Slevin, M., et al. (2022). Polydatin prevents neuroinflammation and relieves depression via regulating sirt1/HMGB1/NF-kappa B signaling in mice. Neurotox. Res. 40 (5), 1393–1404. doi:10.1007/s12640-022-00553-z

Boghrati, Z., Zibaee, E., Ayati, Z., Amiri, S., Ramezani, M., Jamialahmadi, T., et al. (2021). Ethnomedicinal uses, phytochemistry and pharmacology of different cichorium species (Asteraceae): a review. Pharmacol. Prop. Plant-Derived Nat. Prod. Implic. Hum. Health 1308, 501–546. doi:10.1007/978-3-030-64872-5_26

CrossRef Full Text | Google Scholar

Borges, F., Fernandes, E., and Roleira, F. (2002). Progress towards the discovery of xanthine oxidase inhibitors. Curr. Med. Chem. 9 (2), 195–217. doi:10.2174/0929867023371229

Bose, B., Badve, V., Hiremath, S., Boudville, N., Brown, G., Cass, A., et al. (2014). Effects of uric acid-lowering therapy on renal outcomes: a systematic review and meta-analysis. Nephrol. Dial. Transplant. 29 (2), 406–413. doi:10.1093/ndt/gft378

Cao, L., Zhao, T., Xue, Y., Xue, L., Chen, Y., Quan, F., et al. (2021). The anti-inflammatory and uric acid lowering effects of Si-Miao-San on gout. Front. Immunol. 12, 777522. doi:10.3389/fimmu.2021.777522

Chen, J., Zhou, J., Wei, S., Xie, J., Wen, P., and Xu, W. (2016). Effect of a traditional Chinese medicine prescription Quzhuotongbi decoction on hyperuricemia model rats studied by using serum metabolomics based on gas chromatography-mass spectrometry. J. Chromatogr. B-Analytical Technol. Biomed. Life Sci. 1026, 272–278. doi:10.1016/j.jchromb.2015.10.031

Chen, K., Chen, H., Faas, M., de Haan, J., Li, H., Xiao, P., et al. (2017). Specific inulin-type fructan fibers protect against autoimmune diabetes by modulating gut immunity, barrier function, and microbiota homeostasis. Mol. Nutr. Food Res. 61 (8). doi:10.1002/mnfr.201601006

Chen, L., and Kang, H. (2014). Antioxidant and enzyme inhibitory activities of plebeian herba ( Salvia plebeia R. Br.) under different cultivation conditions. J. Agric. Food Chem. 62 (10), 2190–2197. doi:10.1021/jf404570s

Chen, Y., Lan, Z., Zhou, Q., Li, F., Zhang, X., Zhang, F., et al. (2011a). Astilbin attenuates hyperuricemia and ameliorates nephropathy in fructose-induced hyperuricemic rats. Planta Medica 77 (16), 1769–1773. doi:10.1055/s-0030-1271135

Chen, Y., Li, C., Duan, S., Yuan, X., Liang, J., and Hou, S. (2019). Curcumin attenuates potassium oxonate-induced hyperuricemia and kidney inflammation in mice. Biomed. Pharmacother. 118, 109195. doi:10.1016/j.biopha.2019.109195

Chen, Y., Yang, J., Rao, Q., Wang, C., Chen, X., Zhang, Y., et al. (2023). Understanding hyperuricemia: pathogenesis, potential therapeutic role of bioactive peptides, and assessing bioactive peptide advantages and challenges. Foods Basel, Switz. 12 (24), 4465. doi:10.3390/foods12244465

Chen, Y., Yin, F., Lan, Z., Ma, W., Zhang, F., Yang, L., et al. (2011b). Anti-hyperuricemic and nephroprotective effects of Smilax china L. J. Ethnopharmacol. 135 (2), 399–405. doi:10.1016/j.jep.2011.03.033

Chen, Y., Zhao, Z., Li, Y., Yang, Y., Li, L., Jiang, Y., et al. (2021). Baicalein alleviates hyperuricemia by promoting uric acid excretion and inhibiting xanthine oxidase. Phytomedicine 80, 153374. doi:10.1016/j.phymed.2020.153374

Cheng, P., Sun, X., Li, M., Yan, M., Peng, H., You, P., et al. (2019). Effects of alismatis rhizoma and rhizoma Smilacis glabrae decoction on hyperuricemia in rats. Evidence-Based Complementary Altern. Med. 2019, 4541609. doi:10.1155/2019/4541609

Chesworth, R., Gamage, R., Ullah, F., Sonego, S., Millington, C., Fernandez, A., et al. (2021). Spatial memory and microglia activation in a mouse model of chronic neuroinflammation and the anti-inflammatory effects of apigenin. Front. Neurosci. 15, 699329. doi:10.3389/fnins.2021.699329

Dragos, D., Manea, M., Timofte, D., and Ionescu, D. (2020). Mechanisms of herbal nephroprotection in diabetes mellitus. J. Diabetes Res. 2020, 5710513. doi:10.1155/2020/5710513

Durazzo, A., Nazhand, A., Lucarini, M., Silva, M., Souto, B., Guerra, F., et al. (2021). Astragalus (Astragalus membranaceus Bunge): botanical, geographical, and historical aspects to pharmaceutical components and beneficial role. Rendiconti Lincei-Scienze Fis. E Nat. 32 (3), 625–642. doi:10.1007/s12210-021-01003-2

Fang, C., Chen, L., He, M., Luo, Y., Zhou, M., Zhang, N., et al. (2019). Molecular mechanistic insight into the anti-hyperuricemic effect of Eucommia ulmoides in mice and rats. Pharm. Biol. 57 (1), 112–119. doi:10.1080/13880209.2019.1568510

Ge, L., Su, G., Wang, H., Zhao, X., Hou, F., Zheng, A., et al. (2023). Identifying the intervention mechanisms of polydatin in hyperuricemia model rats by using UHPLC-Q-Exactive Orbitrap mass spectroscopy metabonomic approach. Front. Nutr. 10, 1117460. doi:10.3389/fnut.2023.1117460

Gu, C., Hu, X., Shan, B., Wu, X., and Chen, J. (2023). Targeted and non-targeted metabolomics uncovering the effects of Er-Miao-Wan formula on rats with hyperuricemia. J. Pharm. Biomed. Anal. 226, 115246. doi:10.1016/j.jpba.2023.115246

Guo, F., Chen, X., Lei, S., Li, B., Zhang, Y., Ge, Z., et al. (2020). Effects and mechanisms of dendrobium officinalis six nostrum for treatment of hyperuricemia with hyperlipidemia. Evidence-Based Complementary Altern. Med. 2020, 2914019. doi:10.1155/2020/2914019

Guo, P., Jiang, Q., Gui, K., and Wang, S. (2015). Chinese herbal formulas Si-Wu-Tang and Er-Miao-San synergistically ameliorated hyperuricemia and renal impairment in rats induced by adenine and potassium oxonate. Cell. Physiology Biochem. 37 (4), 1491–1502. doi:10.1159/000438517

Hong, Q., Yu, D., Mei, Y., Lv, Y., Chen, P., Wang, D., et al. (2014). Smilacis glabrae rhizoma reduces oxidative stress caused by hyperuricemia via upregulation of catalase. Cell. Physiology Biochem. 34 (5), 1675–1685. doi:10.1159/000366369

Hooda, S., Pal, R., Bhandari, A., and Singh, J. (2014). Antihyperglycemic and antihyperlipidemic effects of Salvadora persica in streptozotocin-induced diabetic rats. Pharm. Biol. 52 (6), 745–749. doi:10.3109/13880209.2013.869607

Hosomi, A., Nakanishi, T., Fujita, T., and Tamai, I. (2012). Extra-renal elimination of uric acid via intestinal efflux transporter BCRP/ABCG2. PLoS One 7 (2), e30456. doi:10.1371/journal.pone.0030456

Hou, W., Chen, J., Shen, D., Chen, Y., Wang, J., Wang, H., et al. (2023). Emodin, a natural anthraquinone, increases uric acid excretion in rats with potassium oxonate-induced hyperuricemia. Pharm. (Basel). 25 (6), 789. doi:10.3390/ph16060789

Hu, Q., Ji, J., Xu, P., Ye, L., Sun, D., Sheng, A., et al. (2023). Isolation and characterization of uric acid-lowering functional components from Polygonum cuspidatum . Food Biosci. 53, 102314. doi:10.1016/j.fbio.2022.102314

Huang, X., Hui, W., Wang, C., Li, P., and Chen, J. (2019). Study on chemical constituents of herbal formula Er Miao Wan and GC-MS based metabolomics approach to evaluate its therapeutic effects on hyperuricemic rats. J. Chromatogr. B-Analytical Technol. Biomed. Life Sci. 1118, 101–108. doi:10.1016/j.jchromb.2019.04.032

Jeong, J., Lim, K., Han, H., Lee, H., Kang, S., and Lee, S. (2022). Extract of Aster glehni ameliorates potassium oxonate-induced hyperuricemia by modulating renal urate transporters and renal inflammation by suppressing TLR4/MyD88 signaling. Food Sci. Biotechnol. 30 (13), 1729–1739. doi:10.1007/s10068-022-01153-5

Jiang, W., Qian, P., Ding, R., Wang, K., Ding, Y., Liu, X., et al. (2017). Metabolomic profiles delineate the effect of Sanmiao wan on hyperuricemia in rats. Biomed. Chromatogr. 31 (2). doi:10.1002/bmc.3792

Jin, R., Xu, H., Duan, H., and Chou, X. (2015). Two new flavones from Salvia plebeia. Nat. Prod. Res. 29 (14), 1315–1322. doi:10.1080/14786419.2014.999241

Johnson, J., Bakris, L., Borghi, C., Chonchol, B., Feldman, D., Lanaspa, A., et al. (2018). Hyperuricemia, acute and chronic kidney disease, hypertension, and cardiovascular disease: report of a scientific workshop organized by the national kidney foundation. Am. J. Kidney Dis. 71 (6), 851–865. doi:10.1053/j.ajkd.2017.12.009

Kim, K., Kim, J., Hyun, M., Lee, S., Kwon, G., Seo, C., et al. (2017). Salvia plebeia extract inhibits xanthine oxidase activity in vitro and reduces serum uric acid in an animal model of hyperuricemia. Planta Medica 83 (17), 1335–1341. doi:10.1055/s-0043-111012

Kurajoh, M., Fukumoto, S., Yoshida, S., Akari, S., Murase, T., Nakamura, T., et al. (2021). Uric acid shown to contribute to increased oxidative stress level independent of xanthine oxidoreductase activity in MedCity21 health examination registry. Sci. Rep. 11 (1), 7378. doi:10.1038/s41598-021-86962-0

Li, P., Huang, W., Liu, F., Zheng, N., Xie, H., Chen, N., et al. (2021). Effect of berberine on hyperuricemia and kidney injury: a network pharmacology analysis and experimental validation in a mouse model. Drug Des. Dev. Ther. 15, 3241–3254. doi:10.2147/Dddt.S317776

Li, Q., Liu, P., Wu, C., Bai, L., Zhang, Z., Bao, Z., et al. (2022). Integrating network pharmacology and pharmacological validation to explore the effect of Shi Wei Ru Xiang powder on suppressing hyperuricemia. J. Ethnopharmacol. 298, 115679. doi:10.1016/j.jep.2022.115679

Lin, Y., Liu, G., Liang, Q., Hu, J., Xu, P., Zhou, J., et al. (2018). Luteolin-4'-O-glucoside and its aglycone, two major flavones of Gnaphalium affine D. Don, resist hyperuricemia and acute gouty arthritis activity in animal models. Phytomedicine 41, 54–61. doi:10.1016/j.phymed.2018.02.002

Lin, Y., Wang, Y., Tang, L., Lee, C., Chan, H., Choi, A., et al. (2022). The extracts of Polygonum cuspidatum root and rhizome block the entry of SARS-CoV-2 wild-type and omicron pseudotyped viruses via inhibition of the S-protein and 3CL protease. Molecules 27 (12), 3806. doi:10.3390/molecules27123806

Lin, Y. C., Chang, C. W., and Wu, C. R. (2015). Anti-nociceptive, anti-inflammatory and toxicological evaluation of Fang-Ji-Huang-Qi-Tang in rodents. BMC Complement. Altern. Med. 15, 10. doi:10.1186/s12906-015-0527-5

Liu, L., Jiang, S., Liu, X., Tang, Q., Chen, Y., Qu, J., et al. (2021). Inflammatory response and oxidative stress as mechanism of reducing hyperuricemia of Gardenia jasminoides-Poria cocos with network pharmacology. Oxid. Med. Cell Longev. 2021, 8031319. doi:10.1155/2021/8031319

Liu, P., Li, X., Yu, B., Huang, J., Sun, J., Huo, S., et al. (2005). Effects of trans-resveratrol from Polygonum cuspidatum on bone loss using the ovariectomized rat model. J. Med. Food 8 (1), 14–19. doi:10.1089/jmf.2005.8.14

Liu, Q., Sun, X., Liu, B., Zhang, T., Zhang, L., and Wu, J. (2022b). Phytochemicals in traditional Chinese medicine can treat gout by regulating intestinal flora through inactivating NLRP3 and inhibiting XOD activity. J. Pharm. Pharmacol. 74 (7), 919–929. doi:10.1093/jpp/rgac024

Liu, T., Gao, H., Zhang, Y., Wang, S., Lu, M., Dai, X., et al. (2022a). Apigenin ameliorates hyperuricemia and renal injury through regulation of uric acid metabolism and JAK2/STAT3 signaling pathway. Pharm. (Basel) 21 (11), 1442. doi:10.3390/ph15111442

Luissint, C., Parkos, A., and Nusrat, A. (2016). Inflammation and the intestinal barrier: leukocyte-epithelial cell interactions, cell junction remodeling, and mucosal repair. Gastroenterology 151 (4), 616–632. doi:10.1053/j.gastro.2016.07.008

Ma, G., Wang, J., Bu, W., Zhang, H., Zhang, P., Zhang, X., et al. (2019). Effects of Polygonum cuspidatum on AMPK-FOXO3 signaling pathway in rat model of uric acid-induced renal damage. Chin. J. Integr. Med. 25 (3), 182–189. doi:10.1007/s11655-017-2979-6

Ma, N., Cai, S., Sun, Y., and Chu, C. (2024). Chinese sumac (rhus chinensis mill.) fruits prevent hyperuricemia and uric acid nephropathy in mice fed a high-purine yeast diet. Nutrients 16 (2), 184. doi:10.3390/nu16020184

Maiuolo, J., Oppedisano, F., Gratteri, S., Muscoli, C., and Mollace, V. (2016). Regulation of uric acid metabolism and excretion. Int. J. Cardiol. 213, 8–14. doi:10.1016/j.ijcard.2015.08.109

Mehmood, A., Zhao, L., Ishaq, M., Xin, W., Zhao, L., Wang, C., et al. (2020). Anti-hyperuricemic potential of stevia ( Stevia rebaudiana Bertoni) residue extract in hyperuricemic mice. Food Funct. 11 (7), 6387–6406. doi:10.1039/c9fo02246e

Meng, J., Tian, J., Zhao, Y., Li, C., Yi, Y., Zhang, Y., et al. (2023). Ameliorative effect of cheqianzi decoction on hyperuricemia and kidney injury and underlying mechanism in rats. Heliyon 9 (4), e15333. doi:10.1016/j.heliyon.2023.e15333

Meng, Q., Yan, X., Tang, H., Guo, R., Li, N., Huang, Z., et al. (2015). Anti-hyperuricemic and nephroprotective effects of rhein in hyperuricemic mice. Planta Medica 81 (4), 279–285. doi:10.1055/s-0034-1396241

Morgan, L., and Singh, A. (2021). How do dietary interventions affect serum urate and gout? Nat. Rev. Rheumatol. 17 (4), 191–192. doi:10.1038/s41584-021-00576-4

Mueller-Heupt, K., Vierengel, N., Gross, J., Opatz, T., Deschner, J., and von Loewenich, D. (2022). Antimicrobial activity of Eucalyptus globulus, Azadirachta indica, Glycyrrhiza glabra, Rheum palmatum extracts and rhein against porphyromonas gingivalis. Antibiotics-Basel 11 (2), 186. doi:10.3390/antibiotics11020186

Naz, H., Naz, S., Miraj, R., Zaheer, A., Azam, N., Mughal, S., et al. (2021). The effect of berberine, a drug from Chinese folk medicine, on serum and urinary uric acid levels in rats with hyperuricemia. Cureus J. Med. Sci. 13 (2), e13186. doi:10.7759/cureus.13186

Qian, W., Jiang, Y., Luo, Y., and Jiang, C. (2023). The anti-hyperuricemia and anti-inflammatory effects of Atractylodes macrocephala in hyperuricemia and gouty arthritis rat models. Comb. Chem. High Throughput Screen. 26 (5), 950–964. doi:10.2174/1386207325666220603101540

Russo, E., Viazzi, F., Pontremoli, R., Barbagallo, C. M., Bombelli, M., Casiglia, E., et al. (2022). Association of uric acid with kidney function and albuminuria: the Uric Acid Right for heArt Health (URRAH) Project. J. Nephrol. 35 (1), 211–221. doi:10.1007/s40620-021-00985-4

Sang, M., Du, Y., Hao, J., Wang, L., Liu, W., Zhang, Y., et al. (2017). Modeling and optimizing inhibitory activities of Nelumbinis folium extract on xanthine oxidase using response surface methodology. J. Pharm. Biomed. Analysis 139, 37–43. doi:10.1016/j.jpba.2017.02.048

Santos, M., Veronese, V., and Moresco, N. (2020). Uric acid and kidney damage in systemic lupus erythematosus. Clin. Chim. Acta 508, 197–205. doi:10.1016/j.cca.2020.05.034

Shahzad, M., Shabbir, A., Wojcikowski, K., Wohlmuth, H., and Gobe, C. (2016). The antioxidant effects of radix Astragali (Astragalus membranaceus and related species) in protecting tissues from injury and disease. Curr. Drug Targets 17 (12), 1331–1340. doi:10.2174/1389450116666150907104742

Shan, B., Chen, T., Huang, B., Liu, Y., and Chen, J. (2021). Untargeted metabolomics reveal the therapeutic effects of Ermiao wan categorized formulas on rats with hyperuricemia. J. Ethnopharmacol. 281, 114545. doi:10.1016/j.jep.2021.114545

Shi, H., Huang, W., Li, C., Liu, W., and Wang, F. (2014). Design, synthesis and molecular modeling of aloe-emodin derivatives as potent xanthine oxidase inhibitors. Eur. J. Med. Chem. 75, 289–296. doi:10.1016/j.ejmech.2014.01.058

Shi, W., Wang, P., Wang, X., Zhang, L., Liu, L., Wang, W., et al. (2012). Uricosuric and nephroprotective properties of Ramulus Mori ethanol extract in hyperuricemic mice. J. Ethnopharmacol. 143 (3), 896–904. doi:10.1016/j.jep.2012.08.023

Song, S., Fan, M., Wen, X., Shi, X., Lou, Y., He, Z., et al. (2023). Integrated network pharmacology and gut microbiome analysis to reveal the mechanism of Qu-Zhuo-Tong-Bi decoction against hyperuricemia and gout. J. Ethnopharmacol. 316, 116736. doi:10.1016/j.jep.2023.116736

Strilchuk, L., Fogacci, F., and Cicero, F. (2019). Safety and tolerability of available urate-lowering drugs: a critical review. Expert Opin. Drug Saf. 18 (4), 261–271. doi:10.1080/14740338.2019.1594771

Sun, M., Lan, P., Tong, C., Zhang, Y., Sun, S., Xiong, Z., et al. (2019). An integrative investigation on the efficacy of Plantaginis semen based on UPLC-QTOF-MS metabolomics approach in hyperlipidemic mice. Biomed. Pharmacother. 115, 108907. doi:10.1016/j.biopha.2019.108907

Teixeira, F., de Souza, J., Dophine, D., de Souza Filho, J. D., and Saúde-Guimarães, D. A. (2022). Chemical analysis of Eruca sativa ethanolic extract and its effects on hyperuricaemia. Molecules 27 (5), 1506. doi:10.3390/molecules27051506

Wang, C., Li, L., Chiu, Y., Chen, C., Chen, C., and Chen, A. (2022b). Protective effects of Corni Fructus extract in mice with potassium oxonate-induced hyperuricemia. J. Vet. Med. Sci. 84 (8), 1134–1141. doi:10.1292/jvms.21-0671

Wang, H., Gao, Z., Li, D., Zhang, Y., Moustaid, K., and Nasser, B. (2020). Genus Ziziphus: a comprehensive review on ethnopharmacological, phytochemical and pharmacological properties. J. Ethnopharmacol. 259, 112950. doi:10.1016/j.jep.2020.112950

Wang, J., Chen, Y., Zhong, H., Chen, F., Regenstein, J., Hu, S., et al. (2022a). The gut microbiota as a target to control hyperuricemia pathogenesis: potential mechanisms and therapeutic strategies. Crit. Rev. Food Sci. Nutr. 62 (14), 3979–3989. doi:10.1080/10408398.2021.1874287

Wang, M., Zhao, J., Zhang, N., and Chen, J. (2016). Astilbin improves potassium oxonate-induced hyperuricemia and kidney injury through regulating oxidative stress and inflammation response in mice. Biomed. Pharmacother. 83, 975–988. doi:10.1016/j.biopha.2016.07.025

Wang, Q., Wang, L., Tu, C., and Zhang, C. (2018). Traditional Chinese medicine for refractory nephrotic syndrome: strategies and promising treatments. Evidence-Based Complementary Altern. Med. 2018, 8746349. doi:10.1155/2018/8746349

Wang, X., Li, X., Ma, H., Zhang, F., and Jia, Q. (2013). Tumoral cytotoxic and antioxidative phenylpropanoid glycosides in Smilax riparia A. DC . J. Ethnopharmacol. 149 (2), 527–532. doi:10.1016/j.jep.2013.07.011

Wang, X., Liu, L., Yang, Y., Zhang, M., and Kong, D. (2015). Nuciferine restores potassium oxonate-induced hyperuricemia and kidney inflammation in mice. Eur. J. Pharmacol. 747, 59–70. doi:10.1016/j.ejphar.2014.11.035

Wang, X., Liu, X., Gao, Q., Gu, X., Zhang, G., Sheng, Z., et al. (2023b). Gegen Qinlian Decoction treatment of asymptomatic hyperuricemia by targeting circadian immune function. Chin. Med. 18 (1), 77. doi:10.1186/s13020-023-00775-z

Wang, Y., Lin, F., Ye, C., Aihemaitijiang, S., Halimulati, M., Huang, J., et al. (2023a). Multi-omics analysis reveals therapeutic effects of Bacillus subtilis-fermented Astragalus membranaceus in hyperuricemia via modulation of gut microbiota. Food Chem. 399, 133993. doi:10.1016/j.foodchem.2022.133993

Wei, B., Xu, C., Liu, S., Song, R., Liu, Q., and Qu, B. (2018). Metabonomics study of the effects of traditional Chinese medicine formula Ermiaowan on hyperuricemic rats. J. Sep. Sci. 41 (2), 560–570. doi:10.1002/jssc.201700985

Wen, H., Lou, Y., Song, Y., He, X., Chen, J., Xie, J., et al. (2021). Qu-Zhuo-Tong-Bi decoction alleviates gouty arthritis by regulating butyrate-producing bacteria in mice. Front. Pharmacol. 11, 610556. doi:10.3389/fphar.2020.610556

Wu, H., Ruan, L., Zhang, J., Wang, Q., and Zhang, W. (2014). Pallidifloside D, a saponin glycoside constituent from Smilax riparia, resist to hyperuricemia based on URAT1 and GLUT9 in hyperuricemic mice. J. Ethnopharmacol. 157, 201–205. doi:10.1016/j.jep.2014.09.034

Wu, H., Wang, Z., Wang, Q., Mi, C., He, Y., Zhang, J., et al. (2015). Anti-hyperuricemia effects of allopurinol are improved by Smilax riparia , a traditional Chinese herbal medicine. J. Ethnopharmacol. 162, 362–368. doi:10.1016/j.jep.2015.01.012

Wu, S., Zhang, D., and Li, K. (2019). Application of metabolomics for unveiling the therapeutic role of traditional Chinese medicine in metabolic diseases. J. Ethnopharmacol. 242, 112057. doi:10.1016/j.jep.2019.112057

Xiang, W., Xia, N., and Xu, L. (2021). UPLC-MS/MS profiling, antioxidant, a-glucosidase inhibitory, cholinesterase inhibitory, and cardiovascular protection potentials of jialing 20 (Morus multicaulis perr.) mulberry branch extract. Foods 10 (11), 2659. doi:10.3390/foods10112659

Xing, W., Ning, X., lei, H., Zhen, C., and Wan, Y. (2020). Study on mechanism of Fangji Huangqi Decoction on hypouricemic effect and renal protection in hyperuricemia mice. China J. Chin. Materia Medica 45 (21), 5248–5255. doi:10.19540/j.cnki.cjcmm.20200630.401

Xu, D., Lv, Q., Wang, X., Cui, X., Zhao, P., Yang, X., et al. (2019). Hyperuricemia is associated with impaired intestinal permeability in mice. Am. J. Physiol. Gastrointest. Liver Physiol. 317 (4), G484–G492. doi:10.1152/ajpgi.00151.2019

Xu, M., Xue, H., Qiao, X., Liao, F., Kong, L., Zhang, F., et al. (2022b). Regulating the imbalance of gut microbiota by Smilax China L. Polyphenols to alleviate dextran sulfate sodium-induced inflammatory bowel diseases. Am. J. Chin. Med. 50 (02), 553–568. doi:10.1142/S0192415x22500215

Xu, Q., Lin, S., Yu, X., Li, P., Mai, T., Cheng, J., et al. (2021). Anti-hyperuricemic and nephroprotective effects of dihydroberberine in potassium oxonate- and hypoxanthine-induced hyperuricemic mice. Front. Pharmacol. 12, 645879. doi:10.3389/fphar.2021.645879

Yan, M., An, Y. T., Li, J., Wu, Z. Z., and Wang, T. (2014). Regulatory effect of leonurus extracts on hyperuricemia in rats. Zhongguo Zhong Yao Za Zhi. 39 (24), 4856–4859. doi:10.4268/cjcmm20142430

Yanai, H., Adachi, H., Hakoshima, M., and Katsuyama, H. (2021). Molecular biological and clinical understanding of the pathophysiology and treatments of hyperuricemia and its association with metabolic syndrome, cardiovascular diseases and chronic kidney disease. Int. J. Mol. Sci. 22 (17), 9221. doi:10.3390/ijms22179221

Yang, F., Shi, J., Wang, T., Qin, K., Wang, X., Guo, Y., et al. (2021). Lipidomics study of the therapeutic mechanism of Plantaginis Semen in potassium oxonate-induced hyperuricemia rat. Bmc Complementary Med. Ther. 21 (1), 175. doi:10.1186/s12906-021-03350-x

Yang, L., Wang, B., Ma, L., and Fu, P. (2022). Traditional Chinese herbs and natural products in hyperuricemia-induced chronic kidney disease. Front. Pharmacol. 13, 971032. doi:10.3389/fphar.2022.971032

Yang, M., Qi, M., Tong, C., Wang, D., Ding, L., Li, Y., et al. (2017). Plantago asiatica L. Seed extract improves lipid accumulation and hyperglycemia in high-fat diet-induced obese mice. Int. J. Mol. Sci. 18 (7), 1393. doi:10.3390/ijms18071393

Yong, Q., Chen, D., Xie, Z., Chen, L., Su, Y., Shuai, O., et al. (2018a). Cordycepin, a characteristic bioactive constituent in cordyceps militaris, ameliorates hyperuricemia through URAT1 in hyperuricemic mice. Front. Microbiol. 9, 58. doi:10.3389/fmicb.2018.00058

Yong, Q., Chen, D., Xie, Z., Chen, L., Su, Y., Shuai, O., et al. (2018b). Hypouricemic effects of Ganoderma applanatum in hyperuricemia mice through OAT1 and GLUT9. Front. Pharmacol. 8, 996. doi:10.3389/fphar.2017.00996

Yong, T., Chen, S., Xie, Y., Shuai, O., Li, X., Chen, D., et al. (2018). Hypouricemic effects of extracts from Agrocybe aegerita on hyperuricemia mice and virtual prediction of bioactives by molecular docking. Front. Pharmacol. 9, 498. doi:10.3389/fphar.2018.00498

Yoon, S., Park, H., Ki, H., and Cho, S. (2016). Effects of extracts from Corylopsis coreana Uyeki (Hamamelidaceae) flos on xanthine oxidase activity and hyperuricemia. J. Pharm. Pharmacol. 68 (12), 1597–1603. doi:10.1111/jphp.12626

Yusnaini, R., Nasution, R., Saidi, N., Arabia, T., Idroes, R., Ikhsan, I., et al. (2023). Ethanolic extract from Limonia acidissima L. Fruit attenuates serum uric acid level via URAT1 in potassium oxonate-induced hyperuricemic rats. Pharm. (Basel). 16 (3), 419. doi:10.3390/ph16030419

Zeng, X., Wang, J., Zhang, W., Zhu, X., Li, M., Huang, H., et al. (2018). Antigout effects of Plantago asiatica : xanthine oxidase inhibitory activities assessed by electrochemical biosensing method. Evidence-Based Complementary Altern. Med. 2018, 1364617. doi:10.1155/2018/1364617

Zhang, G., Du, D., Li, F., Zhang, C., Yang, L., Yang, L., et al. (2019b). Constituents and anti-hyperuricemia mechanism of traditional Chinese herbal formulae erding granule. Molecules 24 (18), 3248. doi:10.3390/molecules24183248

Zhang, J., Zhao, Y., Chang, K., Cao, Y., Wang, S., Kang, Z., et al. (2021b). Atractylodis Rhizoma : a review of its traditional uses, phytochemistry, pharmacology, toxicology and quality control. J. Ethnopharmacol. 266, 113415. doi:10.1016/j.jep.2020.113415

Zhang, L., Zhang, J., Zhu, F., Guan, Y., Yang, X., He, X., et al. (2021a). Antihyperuricemia and antigouty arthritis effects of Persicaria capitata herba in mice. Phytomedicine 93, 153765. doi:10.1016/j.phymed.2021.153765

Zhang, M., Zhu, X., Wu, J., Huang, J., Zhao, P., Zhang, X., et al. (2022). Prevalence of hyperuricemia among Chinese adults: findings from two nationally representative cross-sectional surveys in 2015-16 and 2018-19. Front. Immunol. 12, 791983. doi:10.3389/fimmu.2021.791983

Zhang, W., Du, W., Li, G., Zhang, C., Yang, W., Yang, S., et al. (2019a). Constituents and anti-hyperuricemia mechanism of traditional Chinese herbal formulae erding granule. Mol. Basel, Switz. 24 (18), 3248. doi:10.3390/molecules24183248

Zhang, Y., Wang, S., Dai, X., Liu, T., Liu, Y., Shi, H., et al. (2023). Simiao San alleviates hyperuricemia and kidney inflammation by inhibiting NLRP3 inflammasome and JAK2/STAT3 signaling in hyperuricemia mice. J. Ethnopharmacol. 312, 116530. doi:10.1016/j.jep.2023.116530

Zhao, H., Gao, Q., Kong, Z., Tang, W., Jiao, Y., Wang, L., et al. (2020). Study on network pharmacological analysis and preliminary validation to understand the mechanisms of Plantaginis semen in treatment of gouty nephropathy. Evidence-Based Complementary Altern. Med. 2020, 8861110. doi:10.1155/2020/8861110

Zhao, M., Zhu, D., Sun-Waterhouse, D., Su, G., Lin, L., Wang, X., et al. (2014). In vitro and in vivo studies on adlay-derived seed extracts: phenolic profiles, antioxidant activities, serum uric acid suppression, and xanthine oxidase inhibitory effects. J. Agric. Food Chem. 62 (31), 7771–7778. doi:10.1021/jf501952e

Zhao, Y., Lu, X., and Lu, J. (2022). The potential of probiotics in the amelioration of hyperuricemia. Food and Funct. 13 (5), 2394–2414. doi:10.1039/d1fo03206b

Zhou, Y., Zeng, Y., Wang, R., Pang, J., Wang, X., Pan, Z., et al. (2024). Resveratrol improves hyperuricemia and ameliorates renal injury by modulating the gut microbiota. Nutrients 16 (7), 1086. doi:10.3390/nu16071086

Zhou, Y., Zhao, M., Pu, Z., Xu, G., and Li, X. (2018). Relationship between oxidative stress and inflammation in hyperuricemia: analysis based on asymptomatic young patients with primary hyperuricemia. Med. Baltim. 97 (49), e13108. doi:10.1097/MD.0000000000013108

Zhu, C., Xu, Y., Liu, H., Wan, C., Li, X., and Tai, L. (2018). The anti-hyperuricemic effect of epigallocatechin-3-gallate (EGCG) on hyperuricemic mice. Biomed. Pharmacother. 97, 168–173. doi:10.1016/j.biopha.2017.10.013

Zuo, Y., He, M., Zuo, Y., Bou-Chacra, N., and Lobenberg, R. (2018). Erding Formula in hyperuricaemia treatment: unfolding traditional Chinese herbal compatibility using modern pharmaceutical approaches. J. Pharm. Pharmacol. 70 (1), 124–132. doi:10.1111/jphp.12840

Keywords: hyperuricemia, Chinese herbal medicine, Chinese herbal formulae, mechanism of action, urate transporter

Citation: Bai H, Zhang Z, Zhu M, Sun Y, Wang Y, Li B, Wang Q and Kuang H (2024) Research progress of treating hyperuricemia in rats and mice with traditional Chinese medicine. Front. Pharmacol. 15:1428558. doi: 10.3389/fphar.2024.1428558

Received: 06 May 2024; Accepted: 01 July 2024; Published: 19 July 2024.

Reviewed by:

Copyright © 2024 Bai, Zhang, Zhu, Sun, Wang, Li, Wang and Kuang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Qiuhong Wang, [email protected] ; Haixue Kuang, [email protected]

† These authors have contributed equally to this work

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

• SUGGESTED TOPICS
• The Magazine
• Newsletters
• Managing Yourself
• Managing Teams
• Work-life Balance
• The Big Idea
• Data & Visuals
• Reading Lists
• Case Selections
• HBR Learning
• Topic Feeds
• Account Settings
• Email Preferences

It’s Time to Do Away with “Dry Promotions”

• Ranya Nehmeh
• Peter Cappelli

An internal talent marketplace can connect top performers with new opportunities and increase their willingness to stick around.

Instead of providing solid career opportunities, all too often companies resort to filling vacancies from outside. And when they do promote people, many employers give them “dry promotions” — more responsibility without more money. This article makes the case for revamping career development. Employers should provide more opportunities — both promotions that offer more pay and lateral moves. Internal marketplaces are one valuable way to help employees with career development.

Marta was a top performer. She had strong qualities that any manager looks for: dependable, reliable, a hard worker, consistently produced quality work. She had been doing the same job for four years. During this time, she had applied to two positions in other divisions of her company to broaden her skills. Both times the jobs went to other candidates in the division. Marta then got a promotion in her own department and a new title but no salary bump. One month later, Marta resigned.

• Ranya Nehmeh is an HR specialist working on topics related to people strategy, human capital, leadership development, and talent management and is the author of The Chameleon Leader: Connecting with Millennials (2019).
• Peter Cappelli is the George W. Taylor Professor of Management at the Wharton School and the director of its Center for Human Resources. He is the author of several books, including Our Least Important Asset: Why the Relentless Focus on Finance and Accounting Is Bad for Business and Employees (Oxford University Press, 2023).

Partner Center

Research-inspired weight-loss bars set to launch

• Travis Williams

22 Jul 2024

• Share on Facebook
• Share on Twitter
• Copy address link to clipboard

Rodent refreshments served as inspiration for Deborah Good’s new recipe for weight loss. 

Good, associate professor of human nutrition, foods, and exercise, had a history of successfully using conjugated linoleic acid (CLA) to treat genetic obesity in mice by adding the compound to their food but had only seen it given to humans in pill form. 

“I was literally looking at the data from my mice and thinking about the fact that it’s in a biscuit for them and thought, why can’t I just have a biscuit that’s tasty with the same benefits,” Good said. 

Fast forward about a year, mix in help from Virginia Tech’s LAUNCH: Center for New Ventures, and Good Family Foods Group LLC has been born. The first product, the CLAW Bar, which stands for Conjugated Linoleic Acid Weight Loss Bar, debuted in three flavors - cranberry orange almond, dark chocolate cherry, and oatmeal chocolate chip cookie dough – this spring.

“LAUNCH has been very supportive, especially on the patent side of things,” Good said. “They really made me think about how I could turn this idea into a product, which was amazing and what we really needed to get started.”

Good’s project was one of nine projects selected by LAUNCH to support in 2024.

CLA is a fatty acid commonly found in meat and dairy, which was initially identified as an anti-cancer compound. 

Good began researching CLA with mice about 20 years ago. She and her colleagues were the first to show it could treat obesity in a mouse model of adult-onset obesity and more recently, successful used it in a mouse model of Prader-Willi syndrome, a human genetic condition that includes onset obesity, pubertal delay, and small gonads. The findings are included in two U.S. and one international patent applications.

Motivated by the idea of producing CLA-supplemented foods for humans, Good attended LAUNCH’s Startup Labs workshop series, and she and her team were accepted to the 2023 Proof-of-Concept Program . The team includes Shadi Ariyanfar, a Ph.D . candidate in the Department of Human Nutrition, Food and Exercise, and Daniel Miglia, owner of Hick’ry Ridge Management and a Culinary Institute of America trained chef.

Along with support to fill the gap between public research funding and early-stage commercialization, the program tasked the team with completing a four-week National Science Foundation course and conducting market research with a variety of potential customers. 

With the help of LAUNCH and contacts like Matt Livingstone at the Virginia Tech Corporate Research Center “Co-Gro” labs, Good and her team also were selected to be a part of the 2023 Fall Life Sciences cohort of the Regional Accelerator and Mentor Program (RAMP), a technology entrepreneurship program in Roanoke, last fall. Verge, a coalition that includes RAMP and the Roanoke-Blacksburg Technology council, provided additional funding while the program provides mentoring and a 12-week intensive curriculum to help jump-start new businesses. 

“Deborah and her team are a great example of how the Proof-of-Concept Program serves as a springboard for much larger grant and research opportunities,” said Mark Mondry, who leads LAUNCH. “Providing Virginia Tech researchers early stage commercialization funding and related innovation support services, helps to validate technology, market applications, and attract future funding from federal agencies, nonprofit organizations, and foundations.”

While LAUNCH and RAMP helped navigate the business processes, it was Good and Miglia, who is also Good’s husband, who journeyed through the product creation process. 

“We sat down at one point last year with Sean O’Keefe and Joell Eifert from the Department of Food Science at Virginia Tech and with a big bag of different types of health food bars and ate and evaluated bars for ingredients, taste, chewiness, etc.,” Good said. “I thought, 'Man, I should have really gone into food research.'”

With plenty of research and experimentation behind them, Good Family Foods Group debuted samples of its three CLAW Bars at the 2024 Virginia Food and Beverage Expo in Richmond in March. Bars for purchase are expected to be available in and around Blacksburg this fall, and the group aims to expand into other lines of food, such as shakes and coffee pods, in the near future.

“This has been a whirlwind of progress that I do not believe would be happening if LAUNCH had not funded our initial proposal,” Good said. “It truly jump-started our capabilities and confidence in launching this company as an offshoot of our research.”

LAUNCH’s Proof-of-Concept Program combines early-stage commercialization grants and complementary resources to assist Virginia Tech researchers in increasing the impact of their research by pursuing the commercialization of technologies emerging from their labs. The program provides competitive grants up to $50,000 and associated resources support these early-stage activities.

The 2024 projects include the following:

Recycling and Upcycling of Plastic Wastes

Post-consumer plastic waste, such as polyethylene, that makes grocery bags and milk jugs is often not recycled, causing environmental challenges. The Liu lab in the Department of Chemistry at Virginia Tech has developed a process to convert polyethylene waste into surfactants and potentially use them as household detergents. 

Team members:

• Guoliang "Greg" Liu, principal investigator and associate professor, Department of Chemistry
• Nuwayo Eric Munyaneza, fourth-year Ph.D. candidate, Department of Chemistry
• Carlos Posada, second-year graduate student, Department of Chemistry 

Prototype Refinement and Customer Discovery for In-Network Intrusion Prevention for Enterprise Network Security

The team is developing a novel network defense system that precisely confines end-to-end information flows and prevents cross-host cyberattacks in real time when the connection is established on the fly.

• Peng Gao, principal investigator and assistant professor, Department of Computer Science
• Bo Ji, associate professor, Department of Computer Science
• Osama Bajaber, Ph.D. student, Department of Computer Science

Dual-Cool Power Modules for Electric Vehicles

This project will accelerate the commercialization of an innovative technology for manufacturing low-cost, dual-cool power modules for traction inverters in electric vehicles. These power modules serve as the pivotal components within the inverter, comprising semiconductor switching devices that regulate the flow of electrical energy from the battery to the motor. 

• Guo-Quan Lu, principal investigator and professor, Department of Materials and Systems Engineering
• Joshua Gardner, Ph.D. student, Department of Materials and Systems Engineering
• Qingrui Yuchi, graduate student, Department of Materials and Systems Engineering

Motorcycle Collision Alert and Management System: Customer Discovery

This project will help reduce motorcycle-related crashes in low- and middle-income countries by providing a safety technology bundle for low-cost, low-capacity motorcycles. 

• Richard Hanowski, principal investigator and director, Division of Freight, Transit, and Heavy Vehicle Safety at the Virginia Tech Transportation Institute 
• Carl Cospel, director, Hardware Engineering Laboratory at the Virginia Tech Transportation Institute

Enhancing Crop Resilience and Sustainability through CRITT Gene Editing Technology

Developed by the group, “CRITT” introduces innovation by using CRISPR (clustered regularly interspaced short palindromic repeats) in conjunction with grafting techniques to modify plants without making them transgenic, thereby preserving the unique qualities of high-value cultivars while enhancing their resilience to environmental stresses. This approach not only promises to improve crop production by ensuring the sustainability and quality of fruits and vegetables but also opens up a new frontier in agricultural technology, significantly impacting food security and climate resilience. 

• Sherif Sherif, principal investigator and associate professor, Department of Plant and Environmental Sciences
• Mohammad Zarrabian, postdoctoral research associate, Department of Plant and Environmental Sciences

CycliCx: A novel drug for the targeted treatment of vascular disease

CycliCx offers a unique solution for patients with narrowed and blocked coronary arteries. Using our patented peptide technology, CycliCx simultaneously promotes healthy vessel repair while preventing excessive cell growth. Ultimately this reduces the risk of heart attacks and mortality, improving overall quality of life.

• Meghan Sedovy, principal investigator and Ph.D. candidate, Fralin Biomedical Research Institute
• Scott Johnstone, assistant professor, Fralin Biomedical Research Institute and the Department of Biological Science
• Mark Renton, postdoctoral associate, Fralin Biomedical Research Institute.

Evaluation of a Wearable Device to Manage Lymphedema

LymphaVibe is dedicated to developing a wearable device to reduce upper extremity lymphedema in breast cancer patients. 

• Chris Arena, principal investigator and collegiate associate professor, Department of Biomedical Engineering and Mechanics
• Andy Muelenaer, professor of practice, Department of Biomedical Engineering and Mechanics
• Tara Newberry, clinical lead, Carilion Clinic Occupational Therapy
• Jenny Munson, associate professor, Department of Biomedical Engineering and Mechanics

Wireless, Field Deployable 3D-printed Sensors for Monitoring Phosphate and Calcium Ions

This project aims to develop lithography-free, low-cost, and wireless sensors using 3D-printed geometries for the continuous detection of ions including phosphate and ionized calcium in river water quality and dairy cows' milk samples.

• Azahar Ali, principal investigator, assistant professo, School of Animal Sciences
• Dong Sam Ha, professor, Bradley Department of Electrical and Computer Engineering

Lindsey Haugh

• College of Agriculture and Life Sciences
• Food Science and Technology
• Fralin Life Sciences Institute
• Human Nutrition, Foods, and Exercise
• LINK+LICENSE+LAUNCH
• School of Neuroscience

Related Content

You are using an outdated browser. Please upgrade your browser to improve your experience.