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To further confirm the involvement of Nrf2, Nrf2 expression was down-regulated by Nrf2 siRNA transfection, which significantly increased the expression of inflammatory factors including IL-6, iNOS, as well as the cartilage matrix degradation factor, MMP13, in chondrocytes treated with metformin

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The formation of metal-flavonoid complexes significantly enhances their bioavailability, positioning these compounds as promising candidates for next-generation therapeutics ( Ehretia tinifolia extract (ETME) counteracts this response by activating the protective Nrf2/HO-1 pathway while suppressing NF-B/MAPK-mediated inflammation

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