Protective effects of luteolin-7-O-glucoside against starvation-induced injury through upregulation of autophagy in H9c2 Cells

Abstract

Cardiomyocyte nutrient deprivation is a common clinical event that mediates various cardiac ischemic processes and is associated with autophagy activation and cell survival or death. Luteolin-7-O-glucoside (LUTG) was one of the flavonoid glycosides isolated from Dracocephalum tanguticum. Previous research had showed that LUTG pretreatment had significant protective effects against doxorubicin-induced cardiotoxicity. However, whether LUTG could protect cardiomyocytes from starvation-induced injury was not clear. In this study, cardioprotection and mechanisms of LUTG against starvation-induced injury were investigated in vitro. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-tetrazolium bromide (MTT) assay showed starvation-induced autophagy is a homeostatic and protective response for H9c2 cell survival. LUTG could protect against injury induced by starvation in H9c2 cells. Acridine orange (AO) staining showed that pretreatment with LUTG enhanced lysosomal autophagy. Western blotting indicated that LUTG enhanced autophagy by down-regulating the expression of phospho-extracellular signal regulated kinase1/2 (p-ERK), phospho-protein kinase B (p-Akt) and phospho-mammalian target of rapamycin (p-mTOR). These results suggest that LUTG might act as a promising therapeutic agent for preventing starvation-induced cardiotoxicity by upregulation of autophagy through the Akt/mTOR and ERK signal pathway.

Keywords: Luteolin-7-O-glucoside (LUTG); autophagy; extracellular signal regulated kinase (ERK); mammalian target of rapamycin (mTOR); starvation.