Robinin attenuates cardiac oxidative stress-induced endoplasmic reticulum-dependent apoptosis through AKT/GSK3β pathway

Robinin通过AKT/GSK3β通路减弱心脏氧化应激诱导的内质网依赖性细胞凋亡。

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Abstract

Myocardial injury is a pathological condition often resulting from excessive β-adrenergic stimulation, such as that induced by isoproterenol (ISO), a β-adrenergic agonist that increases reactive oxygen species (ROS) production, leading to endoplasmic reticulum (ER) stress, apoptosis, and impaired survival signaling. This study investigated Robinin's (Rob) ability to mitigate ISO-induced myocardial damage in H9c2 cardiomyocytes and male Sprague-Dawley rats. ISO-induced damage was assessed through histology, oxidant/antioxidant assays, cardiac marker enzyme assays, and molecular analyses, including PCR and Western blotting. Rob treatment significantly reduced ISO-induced ROS generation and apoptosis, while preserving cell morphology and survival. Rob also modulated ER stress and apoptosis-related proteins, restoring cardiomyocyte function in a dose-dependent manner. Western blot analysis confirmed Rob's inhibition of ER stress-mediated apoptosis in both in vitro and in vivo models. These findings suggest that Rob exerts potent cardioprotective effects by reducing oxidative stress, modulating ER stress, and inhibiting apoptosis. Its ability to restore ER function and cardiomyocyte viability highlights its potential as a therapeutic agent for ISO-induced myocardial damage.

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