Asiaticoside alleviates cardiomyocyte apoptosis and oxidative stress in myocardial ischemia/reperfusion injury via activating the PI3K-AKT-GSK3β pathway in vivo and in vitro

Abstract

Background: Myocardial ischemia/reperfusion (MI/R) is one of the most important links in myocardial injury, causing damage to cardiac tissues including cell apoptosis, oxidative stress, and other serious consequences. Asiaticoside (AS), a new compound synthesized from genistein, is cardioprotective. This paper presents new evidence for the protective role of AS against MI/R injury in vitro and in vivo. Methods: First, BALB/c mice underwent surgical ligation of the left anterior descending (LAD) artery to establish an MI/R animal model, and HL-1 cells were subjected to oxygen-glucose deprivation/ reperfusion (OGD/R) to establish an in vitro model. Myocardial infarct size was examined by triphenyl tetrazolium chloride (TTC) staining, histopathological changes detected in heart tissues were observed using hematoxylin and eosin (H&E) and Masson staining, heart tissue apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Enzyme-linked immunosorbent assay (ELISA) kits were used to analyze cardiac troponin I (CTnI), creatine kinase-muscle and brain (CK-MB), lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA), and reduced glutathione (GSH). Cell viability was evaluated using Cell Counting Kit-8 (CCK-8) and live/dead assay. Cell apoptosis, reactive oxygen species (ROS), mitochondrial membrane potential, and mitochondrial superoxide were detected by flow cytometry and fluorescence microscopy. Both the protein expression in myocardial tissues and cardiomyocytes were examined by western blot. Results: In the in vivo MI/R experiments，pretreatment of AS reduced myocardial infarct size, decrease leakage of myocardial enzyme, suppressed myocardial apoptosis, myocardial collagen deposition, and oxidative stress. In the in vitro OGD/R experiments, HL-1 cells pretreated with AS had increased cell viability, decreased apoptosis rates and depolarization of mitochondrial membrane potential, and attenuated intracellular ROS and mitochondrial superoxide. Moreover, AS downregulated the expression of apoptotic protein, and promoted phosphorylation of PI3K, AKT, and GSK3β, which was reversed by PI3K inhibitor LY294002. Conclusions: The AS compound protects against MI/R injury by attenuating oxidative stress and apoptosis via activating the PI3K/AKT/GSK3β pathway in vivo and vitro.

Asiaticoside attenuates oxygen–glucose deprivation/reoxygenation‐caused injury of cardiomyocytes by inhibiting autophagy

“…Multiple evidences have showed the correlation between myocardial injury and increased CK, CK-MB and cTnl (Ren, Xiao, et al, 2019;Tong et al, 2019;Zhou et al, 2019). Previous reports supported that asiaticoside alleviated OGD/R-induced injury in H9c2 and HL-1 cardiomyocytes and ischemia/reperfusioninduced cardiac damage in a mouse model of myocardial ischemia/ reperfusion (Zeng et al, 2022;Zhang, Yao, et al, 2020). Consistent to above studies, our current study also confirmed the cardioprotective function of asiaticoside in OGD/R-stimulated AC16 cardiomyocytes.…”

Cardioprotective effects of asiaticoside against diabetic cardiomyopathy: Activation of the AMPK/Nrf2 pathway

“…Myocardial fibrosis, cardiac systolic and diastolic dysfunction and heart failure are often seen pathophysiologically 6–8 . Recent studies have focused attention on autophagy as a mechanism of DCM 10,16 . Studies have shown that mitochondrial structural damage, mitochondrial dysfunction, and mitochondrial autophagy are associated with diabetic heart disease.…”

“…It has been confirmed that it has antioxidant, anti‐inflammatory, antiviral, wound‐healing promoting and other pharmacological effects 14,15 . The researchers found that the ASI compound protects against myocardial ischaemia/reperfusion injury adjustment by attenuating oxidative stress and apoptosis by activating the PI3K/AKT/GSK3 β pathway in vivo and in vitro 16 …”

“…14,15 The researchers found that the ASI compound protects against myocardial ischaemia/reperfusion injury adjustment by attenuating oxidative stress and apoptosis by activating the PI3K/AKT/GSK3 β pathway in vivo and in vitro. 16 In this study, streptozotocin (STZ) combined with a high-fat diet (HFD) was used to induce the DCM mice model, and ASI was used as an intervention to explore the protective effect of ASI on DCM myocardial injury and the regulation of 5'adenosine monophosphateactivated protein kinase/nuclear factor-erythroid 2-related factor 2 (AMPK/Nrf2) signalling.…”

Electroacupuncture Mediates Fat Metabolism and Autophagy via a Sirt3‐Dependent Mechanism in Mice Fed High‐Fat Diet

“…[2] Current guidelines recommend obesity treatment only for caloric restriction since weight-loss drugs have serious safety risks, among which adverse events of cardiovascular and psychiatric diseases are prominent, resulting in difficulty for drug treatment. [3,4] Electroacupuncture (EA) has a clear effect on weight loss and no side effects and can reduce the risk of various complications. [5] At present, EA has made great progress in the treatment of obesity.…”