Abstract

Mogroside IIe is primarily present in the unripe fruit of Siraitia grosvenorii (Swingle) C. Jeffrey, and it is the predominant saponin component. The purpose of this study was to investigate the effects of mogroside IIe (MGE IIe) on myocardial cell apoptosis in diabetic cardiomyopathy (DCM) rats by establishing a high-sugar and high-fat diet–induced model of type 2 diabetes (T2D) in SD rats and a homocysteine (Hcy)-induced apoptotic model in rat H9c2 cardiomyocytes. The results showed that MGE IIe decreased the levels of fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels, but increased the levels of high-density lipoprotein (HDL) in the SD rat model. Furthermore, MGE IIe decreased the levels of lactate dehydrogenase 2 (LDH2), creatine phosphokinase isoenzyme (CKMB), and creatine kinase (CK), and improved heart function. Additionally, MGE IIe inhibited the secretion of interleukin-1 (IL-1), IL-6, and tumor necrosis factor-α (TNF-α), improved myocardial morphology, and reduced myocardial apoptosis in the SD rat model. Furthermore, MGE IIe inhibited the mRNA and protein expression of active-caspase-3, -8, -9, -12, and Bax and Cyt-C, and promoted the mRNA and protein expression of Bcl-2 in the SD rat model. Furthermore, MGE IIe suppressed homocysteine-induced apoptosis of H9c2 cells by inhibiting the activity of caspases-3, -8, -9, and -12. In conclusion, MGE IIe inhibits the apoptotic pathway, thereby relieving DCM in vivo and in vitro.

Highlights

  • Diabetic cardiomyopathy (DCM) generally refers to diabetes-related myocardial dysfunction in the absence of other apparent causes

  • The results showed that the blood sugar, total cholesterol (TC), TG, and low-density lipoprotein (LDL) levels had significantly increased, whereas the high-density lipoprotein (HDL) level had markedly decreased in the diabetic cardiomyopathy (DCM) model group compared to those in the control group (Supplementary Data A,B)

  • The results showed that the ratio of heart weight to body weight and biochemical factors LDH1, CKMB, and creatine kinase (CK) were markedly increased in the DCM model group compared to those in the control group (Supplementary Data C,D)

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Summary

Introduction

Diabetic cardiomyopathy (DCM) generally refers to diabetes-related myocardial dysfunction in the absence of other apparent causes. DCM is one of the most long-lasting cardiovascular diseases and has generated much interest in recent years (Shetty et al, 2018; Zheng et al, 2018). Clinical manifestations of DCM include metabolic disorders, myocardial cell abnormalities, and microvascular lesions. These manifestations further myocardial cell apoptosis and myocardial fibrosis, and lead to ventricular wall stiffness and cardiac function damage, resulting in heart failure and eventually death in severe cases (Song et al, 2017; Yu et al, 2017). DCM manifests as metabolic disorders and Mogroside IIe Ameliorates Type 2 Diabetic Cardiomyopathy cardiomyocytes abnormalities that are related to cardiomyocyte apoptosis (Cuomo et al, 2019).

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