The effect of Chinese herbs and its effective components on coronary heart disease through PPARs-PGC1α pathway

Abstract

BackgroundDanQi pill (DQP) is prescribed widely in China and has definite cardioprotective effect on coronary heart disease. Our previous studies proved that DQP could effectively regulate plasma levels of high density lipoprotein (HDL) and low density lipoprotein (LDL). However, the regulatory mechanisms of DQP and its major components Salvianolic acids and Panax notoginseng saponins (DS) on lipid metabolism disorders haven’t been comprehensively studied so far.MethodsRat model of coronary heart disease was induced by left anterior descending (LAD) artery ligation operations. Rats were divided into sham, model, DQP treated, DS treated and positive drug (clofibrate) treated groups. At 28 days after surgery, cardiac functions were assessed by echocardiography. Expressions of transcription factors and key molecules in energy metabolism pathway were measured by reverse transcriptase polymerase chain reaction or western blotting.ResultsIn ischemic heart model, cardiac functions were severely injured but improved by treatments of DQP and DS. Expression of LPL was down-regulated in model group. Both DQP and DS could up-regulate the mRNA expression of LPL. Membrane proteins involved in lipid transport and uptake, such as FABP4 and CPT-1A, were down-regulated in ischemic heart tissues. Treatment with DQP and DS regulated lipid metabolisms by up-regulating expressions of FABP4 and CPT-1A. DQP and DS also suppressed expression of cytochrome P450. Furthermore, transcriptional factors, such as PPARα, PPARγ, RXRA and PGC-1α, were down-regulated in ischemic model group. DQP and DS could up-regulate expressions of these factors. However, DS showed a better efficacy than DQP on PGC-1α, a coactivator of PPARs. Key molecules in signaling pathways such as AKT1/2, ERK and PI3K were also regulated by DQP and DS simultaneously.ConclusionsSalvianolic acids and Panax notoginseng are the major effective components of DanQi pill in improving lipid metabolism in ischemic heart model. The effects may be mediated by regulating transcriptional factors such as PPARs, RXRA and PGC-1α.

Mechanism of tanshinones and phenolic acids from Danshen in the treatment of coronary heart disease based on co-expression network

“…PPARA is a ligand-activated transcription factor, which expression by macrophages has antiatherogenic effects by modulation of cell cholesterol trafficking and inflammatory activity [57]. It is reported that salvianolic acids are the major effective components of DanQi pill in improving lipid metabolism in ischemic heart model, which may be mediated by regulating transcriptional factors such as PPARs, RXRA and PGC-1 alpha [58]. These indicate that water-soluble compounds extracted form Danshen may regulate lipid metabolism in coronary atherosclerotic heart disease by INS, PPARA.…”

Panax notoginseng Saponins for Treating Coronary Artery Disease: A Functional and Mechanistic Overview

“…Fatty acid binding protein 4 (FABP4) and CPT-1A, were downregulated in ischemic zone of the heart. PNS could regulate lipid metabolism by increasing the expression of FABP4 and CPT-1A (Wang Q. et al, 2016 ).…”

“…PGC-1α is a transcriptional coactivator of the PPARs and a critical factor in myocardial metabolism (Huss et al, 2004 ). In ischaemic rats, transcriptional factors were downregulated such as PPARs, RXRA, and PGC-1 alpha (Wang Q. et al, 2016 ). PNS could up-regulate expressions of these factors.…”

Danqi Pill Protects Against Heart Failure Post-Acute Myocardial Infarction via HIF-1α/PGC-1α Mediated Glucose Metabolism Pathway

“…Danqi Pill (DQP) is a well-known Chinese patent medicine and used in treating coronary heart disease (Wang et al, 2016). However, the potential pharmacological mechanism of DQP on glucose metabolism remains unknown.…”