Medicinal Plant Research 2025, Vol.15, No.4, 169-177 http://hortherbpublisher.com/index.php/mpr 169 Feature Review Open Access The Role of Gut Microbiota in Modulating Ginseng Pharmacokinetics and Pharmacodynamics Ziyi Dong 1, Baofu Huang 2 1 Institute of Life Science, Jiyang College of Zhejiang A&F University, Zhuji, 311800, Zhejiang, China 2 Traditional Chinese Medicine Research Center, Cuixi Academy of Biotechnology, Zhuji, 311800, Zhejiang, China Corresponding author: baofu.huang@cuixi.org Medicinal Plant Research, 2025, Vol.15, No.4 doi: 10.5376/mpr.2025.15.0018 Received: 20 May, 2025 Accepted: 22 Jun., 2025 Published: 20 Jul., 2025 Copyright © 2025 Dong and Huang, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Dong Z.Y., and Huang B.F., 2025, The role of gut microbiota in modulating ginseng pharmacokinetics and pharmacodynamics, Medicinal Plant Research, 15(4): 169-177 (doi: 10.5376/mpr.2025.15.0018) Abstract Ginseng (Panax spp.) is a most widely employed traditional Chinese medicine herb, valued for its multiradical pharmacological actions, including immunomodulatory, anti-inflammatory, neuroprotective, and anticancer activities. However, the pharmacokinetics (PK) and pharmacodynamics (PD) of ginseng are highly individualized in humans, mainly regulated by gut microbiota. Increasingly, evidence shows that gut microbiota plays a crucial role in the metabolism and biotransformation of ginseng constituents, particularly ginsenosides, through their transformation into bioactive metabolites such as Compound K, thereby enhancing absorption and bioavailability. Gut microbiota is also involved in regulating the pharmacological effects of ginseng, including immune function regulation, oxidative stress modulation, gut–brain axis communication, and anticancer activities. Emerging advances in multi-omics and systems biology approaches, such as metabolomics, metagenomics, and network pharmacology, have cumulatively improved our understanding of the microbe–ginseng interaction network. Differences in composition of gut microbiota among individuals are responsible for significant differences in ginseng efficacy, and population stratification, precision medicine, and microbiota-guided intervention could all become choices to improve clinical effects. Besides, integrating ginseng therapy with probiotics, prebiotics, and microbiota modulators is promising to enhance therapeutic effects and ensure safety. This review comprehensively summarizes the regulatory function of gut microbiota in ginseng PK and PD, demonstrating its importance in personalized herbal medicine and translational uses in the future. Keywords Panax spp.; Gut microbiota; Pharmacokinetics; Pharmacodynamics; Personalized medicine 1 Introduction Ginseng (Panax spp.) is one of the best-known and best-established of the traditional Chinese medicines (TCM) and has been officially considered an elite tonic for millennia. Their bioactive ingredients, particularly ginsenosides, possess diverse pharmacological actions including immunomodulatory, anti-inflammatory, neuroprotective, antioxidant, and antitumor activities. Clinically, ginseng and its products are extensively utilized in the treatment of fatigue, metabolic syndromes, cardiovascular illness, neurological diseases, and adjuvant therapy for cancer therapy. Its multifaceted uses reflect its pharmaceutical potential and increasing inclusion in contemporary global healthcare systems (Iqbal et al., 2024). Pharmacokinetics (PK) and pharmacodynamics (PD) are fundamental to the understanding of TCM medicines such as ginseng's therapeutic effects and safety. PK characterizes the absorption, distribution, metabolism, and excretion of active constituents, whereas PD characterizes their effect in terms of biological activity and dose–response. Given the structural complexity of ginsenosides and their generally poor oral bioavailability, PK and PD understanding becomes essential in elucidating mechanisms of action of ginseng, optimizing its clinical effectiveness, and optimal dosage and formulation design (Chen et al., 2022). The recent advances in microbiome science have revealed the gut microbiota as a critical regulator of the efficacy of herbal medicine. The gut microbiota not only transforms ginsenosides into more bioactive and bioavailable metabolites, such as compound K, but also regulates host signal transduction pathways, immune responses, and system pharmacology effects. Also, inter-subject variation in gut microbial composition is a principal factor
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