Cardioprotection of Panax Notoginseng saponins against acute myocardial infarction and heart failure through inducing autophagy

• Published in: Biomedicine & pharmacotherapy Vol. 136; p. 111287
• Main Authors: Wang, Dandan, Lv, Linyan, Xu, Yue, Jiang, Kai, Chen, Feng, Qian, Jie, Chen, Ming, Liu, Guanping, Xiang, Yaozu
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.04.2021
• Subjects: AMP-Activated Protein Kinases - metabolism; Angiogenesis; Animals; Autophagy; Autophagy - drug effects; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism; Cardiovascular Agents - isolation & purification; Cardiovascular Agents - pharmacology; Cell Line; Disease Models, Animal; Heart Failure - metabolism; Heart Failure - pathology; Heart Failure - physiopathology; Heart Failure - prevention & control; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Mice; Mice, Inbred C57BL; Myocardial infarction; Myocardial Infarction - metabolism; Myocardial Infarction - pathology; Myocardial Infarction - physiopathology; Myocardial Infarction - prevention & control; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Neovascularization, Physiologic - drug effects; Panax notoginseng - chemistry; Panax Notoginseng saponins; Phosphorylation; Platelet; Platelet Aggregation - drug effects; Rats; Saponins - isolation & purification; Saponins - pharmacology; Signal Transduction; Myocardial infarction; Angiogenesis; Panax Notoginseng saponins; Platelet; Autophagy
• ISSN: 0753-3322; 1950-6007; 1950-6007
• DOI: 10.1016/j.biopha.2021.111287

Schematic representation of PNS against MI and heart failure. [Display omitted] •PNS exerts cardioprotective effect in acute MI through inducing autophagy.•PNS induced autophagy through phosphorylation of AMPK and CaMKII in cardiomyocytes.•PNS inhibited platelet aggregation but less affecting on coagulation.•PNS and its main constituents Rg1 and R1 enhanced angiogenesis during MI injury. Morbidity and mortality from acute myocardial infarction (AMI) remains substantial although interventional coronary reperfusion strategies are widely use and successful. MI remains the most common cause of heart failure (HF) worldwide. Here we demonstrated that Panax Notoginseng saponins (PNS), the extract of Panax notoginseng, exerts cardioprotective effect in AMI and the underlying mechanism refers to inducing cardiomyocyte autophagy, antiplatelet aggregation, enhancing endothelial migration and angiogenesis. PNS was initially tested to rescue the myocardial infarct size and cardiac function in left anterior descending (LAD) ligation-operated mice to mimic AMI. RNA-seq to profile transcriptome changes in the heart by treatment with PNS were then conducted. PNS and its main constituents Rg1 and Rd directly inhibited platelet aggregation of healthy subjects with VerifyNow Aspirin and P2Y12 assays but less affecting on coagulation compared with dual-antiplatelet (DAPT). In addition, wound healing scratch assay and heart staining demonstrated that PNS and its main constituents Rg1 and R1 significant enhanced the migration of endothelial cells and angiogenesis in response to MI injury. Interestingly, PNS rather than its constituents enhanced glucose deprivation (GD)-induced autophagy through phosphorylation of AMPK Thr172 and CaMKII Thr287 in cardiomyocytes. These findings provide new insights for drug development from natural products like PNS against ischemia heart diseases and HF post MI.