Diosgenin Attenuates Myocardial Cell Apoptosis Triggered by Oxidative Stress through Estrogen Receptor to Activate the PI3K/Akt and ERK Axes
Michael Yu‐Chih Chen, Bruce Chi‐Kang Tsai, Wei‐Wen Kuo, Chia‐Hua Kuo, Yueh‐Min Lin, Dennis Jine‐Yuan Hsieh, Pei‐Ying Pai, Shih-Chieh Liao, Shang‐En Huang, Shin‐Da Lee, Chih‐Yang Huang
Abstract
Cardiovascular diseases in post-menopausal women are on a rise. Oxidative stress is the main contributing factor to the etiology and pathogenesis of cardiovascular diseases. Diosgenin, a member of steroidal sapogenin, is structurally similar to estrogen and has been shown to have antioxidant effects. Therefore, we aimed to investigate the effects of diosgenin in preventing oxidation-induced cardiomyocyte apoptosis and assessed its potential as a substitute substance for estrogen in post-menopausal women. Apoptotic pathways and mitochondrial membrane potential were measured in H9c2 cardiomyoblast cells and neonatal cardiomyocytes treated with diosgenin for 1[Formula: see text]h prior to hydrogen peroxide (H 2 O 2 ) stimulation. H 2 O 2 -stimulated H9c2 cardiomyoblast cells displayed cytotoxicity and apoptosis via the activation of both Fas-dependent and mitochondria-dependent pathways. Additionally, it led to the instability of the mitochondrial membrane potential. However, the H 2 O 2 -induced H9c2 cell apoptosis was rescued by diosgenin through IGF1 survival pathway activation. This led to the recovery of the mitochondrial membrane potential by suppressing the Fas-dependent and mitochondria-dependent apoptosis. Diosgenin also inhibited H 2 O 2 -induced cytotoxicity and apoptosis through the estrogen receptor interaction with PI3K/Akt and extracellular regulated protein kinases 1/2 activation in myocardial cells. In this study, we confirmed that diosgenin attenuated H 2 O 2 -induced cytotoxicity and apoptosis through estrogen receptors-activated phosphorylation of PI3K/Akt and ERK signaling pathways in myocardial cells via estrogen receptor interaction. All results suggest that H 2 O 2 -induced myocardial damage is reduced by diosgenin due to its interaction with estrogen receptors to decrease the damage. Herein, we conclude that diosgenin might be a potential substitute substance for estrogen in post-menopausal women to prevent heart diseases.