Schisandrol A Attenuates Myocardial Ischemia/Reperfusion-Induced Myocardial Apoptosis through Upregulation of 14-3-3θ

Schisandrol A (SA), one of the most abundant bioactive lignans extracted from the Schisandra chinensis (Turcz.) Baill., has multiple pharmacological properties. However, the underlying mechanisms of SA in protection against myocardial ischemia/reperfusion (MI/R) injury remain obscure. The present experiment was performed to explore the cardioprotective effects of SA in MI/R injury and hypoxia/reoxygenation- (H/R-) induced cardiomyocyte injury and clarify the potential underlying mechanisms. SA treatment significantly improved MI/R injury as reflected by reduced myocardium infarct size, attenuated histological features, and ameliorated biochemical indicators. In the meantime, SA could profoundly ameliorate oxidative stress damage as evidenced by the higher glutathione peroxidase (GSH-Px) as well as lower malondialdehyde (MDA) and reactive oxygen species (ROS). Additionally, SA alleviated myocardial apoptosis as evidenced by a striking reduction of cleaved caspase-3 expression and increase of Bcl-2/Bax ratio. Further experiments demonstrated that SA had certain binding capability to the key functional protein 14-3-3 theta. Mechanistically, SA prevented myocardial apoptosis through upregulating 14-3-3 theta expression. Interestingly, siRNA against 14-3-3 theta could promote apoptosis of cardiomyocytes, and H/R injury after knockdown of 14-3-3 theta could further aggravate apoptosis, while overexpression of 14-3-3 theta could significantly reduce apoptosis induced by H/R injury. Further, 14-3-3 theta siRNA markedly weakened the antiapoptotic role of SA. Our results demonstrated that SA could exert apparent cardioprotection against MI/R injury and H/R injury, and potential mechanisms might be associated with inhibition of cardiomyocyte apoptosis at least partially through upregulation of 14-3-3 theta.

Automated summary

Schisandrol A (SA) extracted from Schisandra chinensis has significant cardioprotective effects against myocardial ischemia/reperfusion (MI/R) injury and hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury. The mechanisms may involve the inhibition of cardiomyocyte apoptosis through upregulation of 14-3-3 theta.