Mechanisms of active metabolites from traditional Chinese medicine in osteoarthritis: a critical review.
- 2026-03-23
- Frontiers in pharmacology 17
- Hui Li
- Yongli Zhao
- Peng Qi
- Bo Zhang
- Jilong Ma
- Xingwen Xie
- Ning Li
- PubMed: 41948727
- DOI: 10.3389/fphar.2026.1786112
Study Design
- Type
- Systematic Review
- Methods
- systematically searched PubMed and Web of Science (2010-2025) for studies on TCM-derived metabolites in OA using keywords such as 'osteoarthritis,' 'Traditional Chinese Medicine,' 'active constituent,' and 'mechanism'; included in vitro, in vivo, and clinical studies based on predefined criteria
Osteoarthritis (OA) is a prevalent degenerative joint disease with multifactorial pathogenesis and no cure. Traditional Chinese Medicine (TCM) is widely used in OA management, and accumulating research suggests that bioactive metabolites (formerly termed active components) from TCM botanical drugs can modulate key pathological processes in OA. Traditional Chinese medicine has an important role in OA management owing to its relatively low incidence of adverse effects, affordability, and multi-target therapeutic actions. In this review, we systematically searched PubMed and Web of Science (2010-2025) for studies on TCM-derived metabolites in OA using keywords such as "osteoarthritis," "Traditional Chinese Medicine," "active constituent," and "mechanism." Relevant in vitro, in vivo, and clinical studies were included based on predefined criteria. We critically evaluated the pharmacological rigor of these studies (models, controls, and translational relevance) and synthesized their findings. Numerous TCM metabolites including flavonoids, polyphenols, saponins, alkaloids, and polysaccharides exhibit chondroprotective effects in preclinical OA models by regulating inflammatory mediators, oxidative stress, cartilage matrix degradation, chondrocyte apoptosis senescence, macrophage polarization, ferroptosis, and gut microbiota composition. These compounds act through pathways such as NF-κB, PI3K/Akt/mTOR, and Wnt/β-catenin, reflecting multi-target mechanisms. Notably, compounds like quercetin and resveratrol are ubiquitous plant metabolites (not unique to TCM) and illustrate structure activity relationships. While promising, most evidence is confined to cell and animal studies with limited clinical validation. We discuss the strengths and limitations of current studies and identify priorities for future research, such as improving bioavailability and conducting high-quality clinical trials. In conclusion, TCM-derived metabolites show potential as multi-target agents for OA, but rigorous clinical studies and advanced delivery strategies are needed to translate these mechanistic insights into effective therapies.