Classification, Structure-Activity Relationship, and Anti-Osteoarthritis Mechanism of Natural Flavonoids

Osteoarthritis is a chronic degenerative joint disease. 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-osteoarthritis. The key structure-activity relationship (SAR) found that the hydroxyl group of o-diphenol/o-triphenol on the B-ring can scavenge free radicals and chelate pro-oxidant metal ions, which directly determines the antioxidant strength; the C2═C3 double bond on the C-ring is conjugated with the 4-carbonyl group to form a rigid planar structure, which can enhance the anti-inflammatory activity; isoflavones linked to C-3 in the B-ring can regulate cartilage metabolism through estrogen receptors. The C-3 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-quality clinical studies and long-term 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.