| Objective To investigate the protective mechanism of luteolin on chondrocytes by regulating PINK1/Parkin mediated mitophagy. Methods Primary rat knee articular chondrocytes were extracted and cultured. The cultured chondrocytes were divided into Control group, IL-1β group (10 ng/mL), low concentration group (25 μmol/L of luteolin), medium concentration group (50 μmol/L of luteolin), high concentration group (100 μmol/L of luteolin), and inhibitor CsA group (50 nmol/L CsA+) 100 μmol/L of luteolin). Cell viability and apoptosis rate were detected using CCK-8 and TUNEL staining. The expression levels of Caspase 9, Caspase 3, PINK1, Parkin, and Cytochrome c were detected with Western blotting. Cell immunofluorescence staining was used to detect the expressions of PINK1 and Parkin. Results Compared to the blank group, IL-1β markedly suppressed chondrocyte viability and promoted apoptosis, evidenced by up-regulated Caspase-9/3 and Cytochrome c, a modest increase in mitophagy, and down-regulated PINK1/Parkin (P<0.05). Compared to the IL-1β group, luteolin dose-dependently restored cell viability, reduced apoptosis, decreased pro-apoptotic proteins, and further enhanced mitophagy along with PINK1/Parkin expression (P<0.05) in low, medium, and high concentration groups. Compared to the high concentration group, co-treatment with CsA significantly blunted the protective effect of luteolin, manifesting as decreased viability, elevated apoptosis, increased pro-apoptotic proteins, attenuated mitophagy, and diminished PINK1/Parkin levels (P< 0.05). Conclusion Luteolin may alleviate chondrocyte injury and inhibit chondrocyte apoptosis through PINK1/ Parkin pathway mediated mitophagy |