Isoorientin ameliorates H(2)O(2)-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.