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The long\u2010term use of non\u2010steroidal anti\u2010inflammatory drugs (NSAIDs) and corticosteroids often leads to adverse side effects like kidney damage and stomach ulcers. Major health threats like obesity and aging create a milieu of chronic low\u2010grade inflammation and increased mechanical stress on the joints resulting in cartilage deterioration. Additionally, postmenopausal women with lower circulating 17\u03b2\u2010estradiol levels experience accelerated joint deterioration due to increased immune activity resulting in the increased production of pro\u2010inflammatory cytokines, with elevated MMP expression and decreased type II collagen synthesis. Polyphenols are nature's gifted magic molecules, which possess diverse biological properties like anti\u2010oxidant, anti\u2010bacterial, anti\u2010inflammatory, estrogenic, and insulin\u2010sensitizing effects, which can manage and treat all the multi\u2010factorial contributing factors of OA effectively. Certain polyphenols can act as phytoestrogens and mimic the effects of natural estrogen by binding to ER\u03b1 and ER\u03b2 and can act as SERMs and prevent degradation of the articular cartilage thereby alleviating osteoarthritic conditions. These molecules downregulate the expression of various pro\u2010inflammatory cytokines, apoptotic genes, and matrix\u2010degrading proteases (MMPs) while upregulating major ECM proteins like type II collagen, aggrecan, and proteoglycans in various osteoarthritic animal models. 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