Myricetin protects cells against oxidative stress-induced apoptosis via regulation of PI3K/Akt and MAPK signaling pathways

Recently, we demonstrated that myricetin exhibits cytoprotective effects against H₂O₂-induced cell damage via its antioxidant properties. In the present study, myricetin was found to inhibit H₂O₂-induced apoptosis in Chinese hamster lung fibroblast (V79-4) cells, as shown by decreased apoptotic bodies, nuclear fragmentation, sub-G1 cell population, and disruption of mitochondrial membrane potential (Δψ_m), which are increased in H₂O₂-treated cells. Western blot data showed that in H₂O₂-treated cells, myricetin increased the level of Bcl-2, which is an anti-apoptotic factor, and decreased the levels of Bax, active caspase-9 and -3, which are pro-apoptotic factors. And myricetin inhibited release of cytochrome c from mitochondria to cytosol in H₂O₂-treated cells. Myricetin-induced survival correlated with Akt activity, and the rescue of cells by myricetin treatment against H₂O₂-induced apoptosis was inhibited by the specific PI3K (phosphoinositol-3-kinase) inhibitor. Myricetin-mediated survival also inhibited the activation of p38 mitogen activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK), which are members of MAPK. Our studies suggest that myricetin prevents oxidative stress-induced apoptosis via regulation of PI3K/Akt and MAPK signaling pathways.