The effect of Astragalus polysaccharides on attenuation of diabetic cardiomyopathy through inhibiting the extrinsic and intrinsic apoptotic pathways in high glucose -stimulated H9C2 cells

Shuqin Sun,Min Dai,Shuo Yang,Qiyan Wang,Zheng Zhang,Xiujuan Jia,Yongjun Mao

doi:10.1186/s12906-017-1828-7

Abstract

BackgroundApoptosis plays a critical role in the progression of diabetic cardiomyopathy (DC). Astragalus polysaccharides (APS), an extract of astragalus membranaceus (AM), is an effective cardioprotectant. Currently, little is known about the detailed mechanisms underlying cardioprotective effects of APS. The aims of this study were to investigate the potential effects and mechanisms of APS on apoptosis employing a model of high glucose induction of apoptosis in H9C2 cells.MethodsA model of high glucose induction of H9C2 cell apoptosis was adopted in this research. The cell viabilities were analyzed by MTT assay, and the apoptotic response was quantified by flow cytometry. The expression levels of the apoptosis related proteins were determined by Real-time PCR and western blotting.ResultsIncubation of H9C2 cells with various concentrations of glucose (i.e., 5.5, 12.5, 25, 33 and 44 mmol/L) for 24 h revealed that cell viability was reduced by high glucose dose-dependently. Pretreatment of cells with APS could inhibit high glucose-induced H9C2 cell apoptosis by decreasing the expressions of caspases and the release of cytochrome C from mitochondria to cytoplasm. Further experiments also showed that APS could modulate the ratio of Bcl-2 to Bax in mitochondria.ConclusionsAPS decreases high glucose-induced H9C2 cell apoptosis by inhibiting the expression of pro-apoptotic proteins of both the extrinsic and intrinsic pathways and modulating the ratio of Bcl-2 to Bax in mitochondria.

Highlights

Apoptosis plays a critical role in the progression of diabetic cardiomyopathy (DC)
Cells were divided into several groups, which were treated with low glucose, high glucose and high glucose combined with Astragalus polysaccharides (APS), respectively
High glucose dose-dependently induced apoptosis in H9C2 cells H9C2 cells were incubated with various concentrations of glucose (5.5, 12.5, 25, 33 and 44 mmol/L) for 24 h and cell viabilities were measured by MTT assay

Summary

Introduction

Apoptosis plays a critical role in the progression of diabetic cardiomyopathy (DC). Astragalus polysaccharides (APS), an extract of astragalus membranaceus (AM), is an effective cardioprotectant. The aims of this study were to investigate the potential effects and mechanisms of APS on apoptosis employing a model of high glucose induction of apoptosis in H9C2 cells. Diabetic cardiomyopathy (DC) is the leading cause of death for diabetic patients. Sun et al BMC Complementary and Alternative Medicine (2017) 17:310 patients, Streptozocin (STZ)-induced diabetic animals and high glucose-treated cardiomyocytes [5,6,7]. Apoptosis is an important contributing factor to pathology in diabetes mellitus. The extent of cardiomyocyte death parallels the severity of the diabetic cardiomyopathy and its stage of evolution [7]. Attenuation of cardiomyocyte apoptosis has been shown to prevent diabetic cardiomyopathy [8, 9]. The mechanisms of apoptosis involved in diabetic cardiomyopathy are not clear. Studies suggest that it may be related to oxidative/nitrative stress and increased production of inflammatory factors such as TNF-α [10,11,12]

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