Wenyang-Yiqi Granule Suppresses Oxygen-Glucose Deprivation-Induced Cardiomyocyte Autophagy Through Mammalian Target of Rapamycin Activation in H9c2 Cells

Abstract Background  Wenyang-Yiqi Granule (WYYQ) is a four-component herbal formula, widely used to treat heart failure in China. It is known to regulate autophagy, but the mechanism(s) are unknown. Methods  H9c2 cells were treated with WYYQ for 24 hours prior to oxygen-glucose deprivation (OGD). Expressions of the autophagy markers Beclin-1 and light chain 3 (LC3) were evaluated via quantitative polymerase chain reaction analysis. Protein levels of Beclin-1, LC3, p62, and mammalian targets of rapamycin (mTOR) were determined by Western blot analysis. Transmission electron microscopy was used to explore the effects of WYYQ on autophagosome formation. Results  Treatment with WYYQ dramatically restrained OGD-induced autophagy, which was characterized by an inhibition of Beclin-1 and increased LC3 mRNA expression. In addition, WYYQ decreased the expression of Beclin-1 and the ratio of LC3-II/LC3-I; however, the abundance of p62 was enhanced at the protein level. Manipulation of the LC3-II/LC3-I ratio, p62 abundance, and autophagosome formation in response to WYYQ were associated with mTOR activity. Conclusions  These findings show that WYYQ plays a protective role during hypoxic-ischemic stress through the suppression of excessive autophagy, which may be partially explained by its effects on mTOR. These data provide novel insight into the cardioprotective effects of WYYQ during cardiomyocyte autophagy.