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

Abstract

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.

• Authors: Dandan Wang, Linyan Lv, Yue Xu, Kai Jiang, Feng Chen, Jie Qian, Ming Chen, Guanping Liu, Yaozu Xiang
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 136 Pg. 111287 (Apr 2021) ISSN: 1950-6007 [Electronic] France
• PMID: 33485065 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Cardiovascular Agents
• Saponins
• Calcium-Calmodulin-Dependent Protein Kinase Type 2
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (metabolism)
• Animals
• Autophagy (drug effects)
• Calcium-Calmodulin-Dependent Protein Kinase Type 2 (metabolism)
• Cardiovascular Agents (isolation & purification, pharmacology)
• Cell Line
• Disease Models, Animal
• Heart Failure (metabolism, pathology, physiopathology, prevention & control)
• Human Umbilical Vein Endothelial Cells (drug effects, metabolism)
• Humans
• Mice, Inbred C57BL
• Myocardial Infarction (metabolism, pathology, physiopathology, prevention & control)
• Myocytes, Cardiac (drug effects, metabolism, pathology)
• Neovascularization, Physiologic (drug effects)
• Panax notoginseng (chemistry)
• Phosphorylation
• Platelet Aggregation (drug effects)
• Rats
• Saponins (isolation & purification, pharmacology)
• Signal Transduction
• Mice