Abstract
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.
Highlights
Coronary heart disease (CHD) often leads to severe cardiac insufficiency, which is a significant challenge to human health
We investigated whether Asiatic acid (AA) exerts cardioprotective effects on myocardial ischemia/reperfusion (I-R) injury (MIRI) by measuring the cardiac function and infarct size of mice after different treatments
We examined the improvement histologically using haematoxylin and eosin (H&E) staining, and the results showed that pretreatment with AA reduced the pathological changes in the myocardial tissue caused by MIRI (Figure 2(c))
Summary
Coronary heart disease (CHD) often leads to severe cardiac insufficiency, which is a significant challenge to human health. Sudden occlusion of coronary arteries during the ischemia phase causes tissue hypoxia and cellular adenosine triphosphate (ATP) depletion, and early reperfusion therapy to restore coronary blood flow after acute myocardial ischemia can save dying cardiomyocytes and prolong survival [1, 2]. Rapid reintroduction of oxygen-rich blood to hypoxic myocardial tissues depleted of oxygen scavengers causes additional damage and aggravates cardiac dysfunction, known as myocardial ischemia/reperfusion (I-R) injury (MIRI) [3, 4]. MIRI is an important pathological factor leading to heart failure in patients with CHD that results in high morbidity and mortality rates [5, 6]. Calcium overload, inflammatory response, and energy metabolism disorders have been shown
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