Asiatic Acid Alleviates Myocardial Ischemia-Reperfusion Injury by Inhibiting the ROS-Mediated Mitochondria-Dependent Apoptosis Pathway

• Published in: Oxidative medicine and cellular longevity 2022, Vol.2022, p.3267450-16
• Main Authors: Yi, Chenlong, Song, Meijuan, Sun, Lifu, Si, Linjie, Yu, Dongmin, Li, Ben, Lu, Peng, Wang, Wei, Wang, Xiaowei
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Apoptosis; Apoptosis - drug effects; Cardiac function; Cardiotonic Agents - pharmacology; Cardiotonic Agents - therapeutic use; Cardiovascular disease; Cells, Cultured; Coronary vessels; Glucose; Heart; Hypoxia; Ischemia; JNK Mitogen-Activated Protein Kinases - metabolism; Laboratory animals; MAP Kinase Signaling System - drug effects; Mice; Mitochondria; Mitochondrial Dynamics - drug effects; Myocardial Ischemia - drug therapy; Myocardial Ischemia - metabolism; Myocardial Ischemia - pathology; Myocardial Reperfusion Injury - drug therapy; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - pathology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Ostomy; Oxidative stress; Oxidative Stress - drug effects; p38 Mitogen-Activated Protein Kinases - metabolism; Pentacyclic Triterpenes - pharmacology; Pentacyclic Triterpenes - therapeutic use; Rats; Reactive oxygen species; Reactive Oxygen Species - metabolism; Thoracic surgery; Veins & arteries
• ISSN: 1942-0900; 1942-0994
• DOI: 10.1155/2022/3267450

Myocardial ischemia-reperfusion injury (MIRI) is a major cause of heart failure in patients with coronary heart disease (CHD). Mitochondrial dysfunction is the crucial factor of MIRI; oxidative stress caused by mitochondrial reactive oxygen species (ROS) aggravates myocardial cell damage through the mitochondria-dependent apoptosis pathway. Asiatic acid (AA) is a type of pentacyclic triterpene compound purified from the traditional Chinese medicine Centella asiatica, and its protective pharmacological activities have been reported in various disease models. This study is aimed at investigating the protective effects of AA and the underlying mechanisms in MIRI. To achieve this goal, an animal model of MIRI in vivo and a cell model of oxygen-glucose deprivation/reperfusion (OGD/R) in vitro were established. The results show that AA exerts a protective effect on MIRI by improving cardiac function and reducing cardiomyocyte damage. Due to its antioxidant properties, AA alleviates mitochondrial oxidative stress, as evidenced by the stable mitochondrial structure, maintained mitochondrial membrane potential (MMP), and reduced ROS generation, otherwise due to its antiapoptotic properties. AA inhibits the mitogen-activated protein kinase (MAPK)/mitochondria-dependent apoptosis pathway, as evidenced by the limited phosphorylation of p38-MAPK and JNK-MAPK, balanced proportion of Bcl-2/Bax, reduced cytochrome c release, inhibition of caspase cascade, and reduced apoptosis. In conclusion, our study confirms that AA exerts cardiac-protective effects by regulating ROS-induced oxidative stress via the MAPK/mitochondria-dependent apoptosis pathway; the results provide new evidence that AA may represent a potential treatment for CHD patients.