To investigate the protective effects and related molecular mechanisms of quercetin (Que) against oxidative stress, inflammatory response, and mitochondrial dysfunction induced by hydrogen peroxide H₂O₂ osteoarthritis (OA) chondrocytes.

Articular chondrocytes were isolated from neonatal rats and randomly divided into a normal control group, a model group (H₂O₂ induced), and a treatment group (Que intervention). The safe concentration of Que was determined by CCK-8 assay. Cell viability was evaluated using Calcein-AM staining. The levels of intracellular ROS, superoxide anion, NO, and mitochondrial membrane potential were detected by DCFH-DA, DHE, DAF-FM DA, and JC-1 fluorescent probes, respectively. The expression of inflammatory factors and matrix-degrading enzymes was measured by immunofluorescence and RT-qPCR.

Que at 10-40 μg/mL showed no obvious cytotoxicity to chondrocytes. Compared with the model group, 40 μg/mL Que significantly increased cell viability (P<0.05), reduced intracellular levels of ROS, superoxide anion, and NO, and ameliorated the H₂O₂ induced decrease in mitochondrial membrane potential (P<0.05). Meanwhile, Que significantly downregulated the protein expression of MMP-13 and IL-6 as well as the mRNA expression of MMP-3, MMP-13, IL-1β, and IL-6 (P<0.05).

Quercetin attenuates H₂O₂ induced oxidative stress and inflammation in chondrocytes by scavenging reactive oxygen species, inhibiting NO production, and maintaining mitochondrial function. It exerts a protective effect on OA chondrocytes and is expected to be a natural candidate for the treatment of osteoarthritis.