AUTHOR=Yan Chao , Du Xiaotao , Liu Yan , Xia Fan , Yu Hongling , Zhu Yongliang , Bao Tianyi TITLE=Efficacy of botanical extracts for knee osteoarthritis: a network meta-analysis of randomized controlled trials JOURNAL=Frontiers in Pharmacology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1619589 DOI=10.3389/fphar.2025.1619589 ISSN=1663-9812 ABSTRACT=BackgroundTraditional botanical drugs and medicinal plants, along with their metabolite extracts, have exhibited considerable potential in the management of knee osteoarthritis (KOA) due to their natural properties, favorable safety profiles, and minimal adverse effects.ObjectiveThis study aimed to evaluate the therapeutic efficacy of various botanical and medicinal plant extracts on KOA. Search Methods: We conducted a comprehensive literature search across PubMed, Embase, Cochrane Library, and Web of Science, focusing exclusively on randomized controlled trials (RCTs) that investigated the efficacy of botanical and medicinal plant extracts for KOA. Selection Criteria: Studies were included if they met the following criteria: (1) experimental groups receiving single botanical drugs or plant extracts for KOA; (2) control groups comprising patients receiving placebo or standard care; (3) clinical RCT designs; and (4) outcome measures including at least one of the following: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Visual Analogue Scale (VAS), Short Form 36 Health Survey (SF-36), Knee injury and Osteoarthritis Outcome Score (KOOS), Lequesne’s Pain-Function Index (LPFI), Japanese Orthopaedic Association Score (JOA). Data Collection and Analysis: The methodological quality of the included studies was assessed using the Cochrane risk of bias tool, and data analysis was performed using appropriate statistical software.ResultsA total of 36 RCTs, encompassing 3,285 participants, were included in this review. Network meta-analysis revealed that compared to the placebo control group, Cucumis sativus (CS) extract [MD = 6.65, 95% CI = (3.83, 9.48)] significantly improved pain scores; Ashwagandha extract [MD = 4.16, 95% CI = (2.43, 5.90)] was more effective in reducing stiffness scores; and CS extract [MD = 4.28, 95% CI = (2.08, 6.49)] significantly improved function scores.ConclusionBased on Ranking Plot of the Network, we can state that CS extract is recommended as the most effective botanical and medicinal plant extract for KOA treatment. However, further studies are required to draw definitive conclusions. Given that there are only two studies with high homogeneity but small sample size for CS extract, the first result should be regarded as an exploratory signal and needs to be verified by a large sample multi-center RCT with independent teams.Clinical Trial Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024617459, identifier CRD42024617459.