Journal Article

Ginsenoside Rg1 ameliorates diabetic cardiomyopathy by inhibiting endoplasmic reticulum stress‐induced apoptosis in a streptozotocin‐induced diabetes rat model

Liu, Quan, Gu, Jinning, Wu, Suisheng, Yu, Haitao, Zhen, Juan, Yang, Yang

2016

Overview

Ginsenoside Rg1 has been demonstrated to have cardiovascular protective effects. However, whether the cardioprotective effects of ginsenoside Rg1 are mediated by endoplasmic reticulum (ER) stress‐induced apoptosis remain unclear. In this study, among 80 male Wistar rats, 15 rats were randomly selected as controls; the remaining 65 rats received a diet rich in fat and sugar content for 4 weeks, followed by intraperitoneal injection of streptozotocin (STZ, 40 mg/kg) to establish a diabetes model. Seven days after STZ injection, 10 rats were randomly selected as diabetic model (DM) controls, 45 eligible diabetic rats were randomized to three treatment groups and administered ginsenoside Rg1 in a dosage of 10, 15 or 20 mg/kg/day, respectively. After 12 weeks of treatment, rats were killed and serum samples obtained to determine cardiac troponin (cTn)‐I. Myocardial tissues were harvested for morphological analysis to detect myocardial cell apoptosis, and to analyse protein expression of glucose‐regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), and Caspase‐12. Treatment with ginsenoside Rg1 (10–20 mg/kg) significantly reduced serum cTnI levels compared with DM control group (all P < 0.01). Ginsenoside Rg1 (15 and 20 mg/kg) significantly reduced the percentage of apoptotic myocardial cells and improved the parameters of cardiac function. Haematoxylin and eosin and Masson staining indicated that ginsenoside Rg1 could attenuate myocardial lesions and myocardial collagen volume fraction. Additionally, ginsenoside Rg1 significantly reduced GRP78, CHOP, and cleaved Caspase‐12 protein expression in a dose‐dependent manner. These findings suggest that ginsenoside Rg1 appeared to ameliorate diabetic cardiomyopathy by inhibiting ER stress‐induced apoptosis in diabetic rats.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Animals / Apoptosis / Apoptosis - drug effects / Calcium-binding protein / Cardiomyopathy / Cardiovascular Agents - pharmacology / Cardiovascular disease / Caspase / Caspase 12 - genetics / Caspase 12 - metabolism / CCAAT/enhancer-binding protein / Collagen / Diabetes / Diabetes mellitus / Diabetes Mellitus, Experimental - chemically induced / Diabetes Mellitus, Experimental - drug therapy / Diabetes Mellitus, Experimental - genetics / Diabetes Mellitus, Experimental - pathology / Diabetic Cardiomyopathies - chemically induced / Diabetic Cardiomyopathies - drug therapy / Diabetic Cardiomyopathies - genetics / Diabetic Cardiomyopathies - pathology / diabetic cardiomyopathy / Diet, High-Fat / Dosage / Dose-Response Relationship, Drug / Endoplasmic reticulum / endoplasmic reticulum stress / Endoplasmic Reticulum Stress - drug effects / Endoplasmic Reticulum Stress - genetics / Gene Expression Regulation / ginsenoside Rg1 / Ginsenosides / Ginsenosides - pharmacology / Glucose / Heart / Heart failure / Heat-Shock Proteins - genetics / Heat-Shock Proteins - metabolism / Homeostasis / Hypoxia / Male / Myocardium - metabolism / Myocardium - pathology / Myocytes, Cardiac - drug effects / Myocytes, Cardiac - metabolism / Myocytes, Cardiac - pathology / Original / Oxidative stress / Pathogenesis / Protein expression / Proteins / Rats / Rats, Wistar / Rodents / Signal Transduction / Streptozocin / Studies / Sugar / Transcription Factor CHOP - genetics / Transcription Factor CHOP - metabolism / Troponin / Troponin I - genetics / Troponin I - metabolism