Epigallocatechin-3-gallate attenuates myocardial fibrosis in diabetic rats by activating autophagy.

Abstract

Epigallocatechin-3-gallate (EGCG) possesses anti-fibrotic potential in diverse tissues; however, the molecular mechanisms underlying the impacts of EGCG on diabetes-induced myocardial fibrosis remain unclear. This present study aimed to unravel the anti-fibrotic effects of EGCG on the heart in type 2 diabetic rats and investigate its molecular mechanisms. Rats were randomly assigned to the following four groups: Normal (NOR), diabetic cardiomyopathy (DCM), DCM + 40 mg/kg EGCG, and DCM + 80 mg/kg EGCG groups. After 8 weeks of EGCG treatment, fasting blood glucose, left ventricular hemodynamic indices, heart index, and myocardial injury-related parameters were measured. Hematoxylin and eosin staining and Sirius Red staining were used to evaluate myocardial pathological alterations and collagen accumulation. The contents of myocardial hydroxyproline, collagen-I, collagen-III, transforming growth factor (TGF)-β1, matrix metalloprotease (MMP)-2, and MMP-9 were measured. The gene expression levels of myocardial TGF-β1, MMP-2, and MMP-9 were detected. Autophagic regulators, including adenosine 5'-monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR), and autophagic markers, including microtubule-associated protein-1 light chain 3 and Beclin1 were estimated. The results indicated that diabetes significantly decreased cardiac contractile function and aggravated myocardial hypertrophy and injury. Furthermore, diabetes repressed the activation of autophagy in myocardial tissue and promoted cardiac fibrosis. Following ingestion with different doses of EGCG, myocardial contractile dysfunction, hypertrophy and injury were ameliorated; myocardial autophagy was activated, and myocardial fibrosis was alleviated in the EGCG treatment groups. In conclusion, these findings suggested that EGCG could attenuate cardiac fibrosis in type 2 diabetic rats, and its underlying mechanisms associated with activation of autophagy via modulation of the AMPK/mTOR pathway and then repression of the TGF-β/MMPs pathway.