Isoorientin ameliorates H2O2-induced apoptosis and oxidative stress in chondrocytes by regulating MAPK and PI3K/Akt pathways

Osteoarthritis (OA) is a chronic and complicated degenerative disease for which there is currently no effective treatment. Isoorientin (ISO) is a natural plant extract that has antioxidant activity and could be used to treat OA. However, due to a lack of research, it has not been widely used. In this study, we investigated the protective effects and molecular mechanisms of ISO on H 2 O 2 -induced chondrocytes, a widely used cell model for OA. Based on RNA-seq and bioinformatics, we discovered that ISO significantly increased the activity of chondrocytes induced by H 2 O 2 , which was associated with apoptosis and oxidative stress. Furthermore, the combination of ISO and H 2 O 2 significantly reduced apoptosis and restored mitochondrial membrane potential (MMP), which may be achieved by inhibiting apoptosis and mitogen-activated protein kinase (MAPK) signaling pathways. Moreover, ISO increased superoxide dismutase (SOD), heme oxygenase 1 (HO-1) and quinone oxidoreductase 1 (NQO-1) and reduced malondialdehyde (MDA) levels. Finally, ISO inhibited H 2 O 2 -induced intracellular reactive oxygen species (ROS) in chondrocytes by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) and phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signaling pathways. This study establishes a theoretical framework for ISO’s ability to inhibit OA in vitro models.