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Naturally derived flavonoids have become a hot spot in the field of osteoarthritis drug research and development. This paper summarizes the classification and chemical structure characteristics of flavonoids and the mechanism of anti\u2010osteoarthritis. The key structure\u2013activity relationship (SAR) found that the hydroxyl group of o\u2010diphenol\/o\u2010triphenol on the B\u2010ring can scavenge free radicals and chelate pro\u2010oxidant metal ions, which directly determines the antioxidant strength; the C2\u2550C3 double bond on the C\u2010ring is conjugated with the 4\u2010carbonyl group to form a rigid planar structure, which can enhance the anti\u2010inflammatory activity; isoflavones linked to C\u20103 in the B\u2010ring can regulate cartilage metabolism through estrogen receptors. The C\u20103 hydroxyl group in flavonols further enhances the free radical scavenging efficiency through intramolecular hydrogen bonds. Although there is sufficient preclinical evidence, the oral bioavailability of most flavonoids is extremely low and there is a lack of high\u2010quality clinical studies and long\u2010term randomized controlled trials. Future research should optimize the structure of compounds based on SAR, and carry out rigorous clinical trials to promote flavonoids from laboratory to clinical application.<\/jats:p>","DOI":"10.1002\/cbdv.71719","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T10:43:01Z","timestamp":1789468981000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Classification, Structure\u2013Activity Relationship, and Anti\u2010Osteoarthritis Mechanism of Natural Flavonoids"],"prefix":"10.1002","volume":"23","author":[{"given":"Haibin","family":"Wang","sequence":"first","affiliation":[{"name":"Inner Mongolia Medical University  Hohhot China"},{"name":"Inner Mongolia Autonomous Region Hospital of Traditional Chinese Medicine  Hohhot China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Inner Mongolia 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