Diosgenin protects H2O2-induced myocardial cells apoptosis via activation of PI3K/Akt signaling through estrogen receptors
Chih-Yang Huang Graduate Institute of Chinese Medical Science, Graduate Institute of Basic Medical Science, China Medical University and Hospital, Taichung 404, Taiwan
Abstract:
The risks of cardiovascular diseases in post-menopausal women were increased. Oxidative stress is one of important contributory factors to the etiology of many cardiovascular diseases. Diosgenin, a member of steroidal sapogenin, structurally similar to estrogen has been shown to have antioxidant effects. The study investigate whether diosgenin directly prevent oxidation-induced cardiomyocyte apoptosis. Apoptotic pathways and mitochondria membrane stabilizing potential were measured in H9c2 cardiomyoblast cells and neonatal cardiomyocytes cultured in serum-free medium for 12 h then pretreated diosgenin for 1 h, subsequently stimulated with H2O2. In this study, H2O2 treated H9c2 cardiomyoblast cells induced cytotoxicity and apoptosis by activated Fas-dependent and mitochondria-dependent pathway. And it also induced instability of mitochondria membrane potential. Further experiment results demonstrated that diosgenin protected H2O2 induced H9c2 cell apoptosis through activated survival pathway (IGF1 signaling) and recovered mitochondria membrane stabilizing potential to suppress Fas-dependent, mitochondria-dependent pathway against apoptosis. And it also inhibited the H2O2-induced cytotoxicity and apoptosis through the estrogen receptors activated phosphorylation of PI3K/Akt and extracellular regulated protein kinases 1/2 (ERK1/2) in myocardial cells. Diosgenin prevented oxidation-induced cardiomyocytes cytotoxicity and apoptosis.
Keywords: Menopause, Traditional Chinese medicine (TCM), Diosgenin, Oxidative stress, Apoptosis
