Compound danshen dripping pills modulate the perturbed energy metabolism in a rat model of acute myocardial ischemia.

Jiahua Guo,Shuiping Zhou,Runbin Sun,Xiangqing Kong,Bei Cao,He Sun,Nan Aa,Lulu Yan,Xiaoyi Yu,Jiye Aa,Jingqiu Huang,Yonghong Yong,Liansheng Wang,Xinxin Li,Na Yang,Jing Cao,Guangji Wang,Zhijian Yang,Zhi‐Xin Guo ,Xue-Ming Zhu ,Xiaojing Ma

doi:10.1038/srep37919

Abstract

The continuous administration of compound danshen dripping pills (CDDP) showed good efficacy in relieving myocardial ischemia clinically. To probe the underlying mechanism, metabolic features were evaluated in a rat model of acute myocardial ischemia induced by isoproterenol (ISO) and administrated with CDDP using a metabolomics platform. Our data revealed that the ISO-induced animal model showed obvious myocardial injury, decreased energy production, and a marked change in metabolomic patterns in plasma and heart tissue. CDDP pretreatment increased energy production, ameliorated biochemical indices, modulated the changes and metabolomic pattern induced by ISO, especially in heart tissue. For the first time, we found that ISO induced myocardial ischemia was accomplished with a reduced fatty acids metabolism and an elevated glycolysis for energy supply upon the ischemic stress; while CDDP pretreatment prevented the tendency induced by ISO and enhanced a metabolic shift towards fatty acids metabolism that conventionally dominates energy supply to cardiac muscle cells. These data suggested that the underlying mechanism of CDDP involved regulating the dominant energy production mode and enhancing a metabolic shift toward fatty acids metabolism in ischemic heart. It was further indicated that CDDP had the potential to prevent myocardial ischemia in clinic.

Highlights

Marketed in many countries (e.g., Canada, Singapore, The United Arab Emirates, Korea, Russia, Cuba, Vietnam, India, and South Africa) as a dietary supplementary for the prevention and treatment of ischemic heart diseases[7]
We provided evidences that CDDP showed distinct modulating effect on energy metabolism induced by myocardial ischemia, i.e., the up-regulation of fatty acids metabolism, and the down-regulation of glycolysis to some extent
ISO increased the levels of free fatty acids and reduced the level of 3-hydroxybutyrate, and reduced glucose and increased pyruvate and TCA intermediates in heart tissue, suggesting the predominant metabolism shift to glycolysis to supply energy

Summary

Introduction

Marketed in many countries (e.g., Canada, Singapore, The United Arab Emirates, Korea, Russia, Cuba, Vietnam, India, and South Africa) as a dietary supplementary for the prevention and treatment of ischemic heart diseases[7]. Previous studies revealed that the pharmacological mechanism of action of CDDP involved modulating platelet and leucocyte function, reducing circulating adhesion molecules, ameliorating myocardial fibrosis, protecting against microcirculatory disturbances, alleviating myocardial damage, and inhibiting NADPH oxidase[8,9,10,11,12,13,14]. These results suggested the ability of CDDP to alleviate the biochemical stress of myocardial ischemia and enhanced our understanding of its therapeutic benefits and underlying mechanisms of action. We analyzed molecules over time in the plasma and heart tissue in the isoproterenol (ISO) induced myocardial ischemia rat model to explore the modulation of metabolic and energy flow by CDDP

Methods

Results

Discussion

Conclusion