Pakistan Journal of Pharmaceutical Sciences

Abstract: Objectives: This study investigates the combined therapeutic effects of myricetin (Myr) and quercetin (Que) on miRNA-140 regulation and the MMP/TIMP signaling pathway involved in cartilage matrix remodeling in osteoarthritis (OA). Methods: In-vitro OA models were established using IL-1?-treated CHON-001 human chondrocytes, while in-vivo OA models were induced by monosodium iodoacetate (MIA) injection in male SD rats. Myr (10??M in-vitro; 25?mg/kg in-vivo), Que (50??M in-vitro; 10?mg/kg in-vivo), or their combination was administered. CCK-8 and TUNEL assays assessed cell viability and apoptosis, while qRT-PCR evaluated miRNA-140 expression. Western blot detected MMP/TIMP proteins and ELISA quantified IL-1?, TNF-?, IL-6 and PGE2 in supernatant and serum samples. Results: Myr and Que individually improved chondrocyte viability and reduced apoptosis, with the combination showing the strongest effect in-vitro. These effects were confirmed in-vivo, where combined treatment alleviated cartilage damage, restored miRNA-140 expression, suppressed MMP-3 and MMP-13 and upregulated TIMP-1 and TIMP-3. TNF-? levels were significantly reduced by co-treatment, while IL-1? and IL-6 showed moderate decreases, indicating synergistic anti-inflammatory and cartilage-protective effects. Conclusion: These findings suggest a miRNA-140-associated regulatory relationship between myricetin/quercetin treatment and MMP/TIMP pathway modulation.