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

BMC Complement Altern Med. 2016 Dec 12;16(1):514. doi: 10.1186/s12906-016-1496-z.

Abstract

Background: DanQi 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.

Methods: Rat 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.

Results: In 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.

Conclusions: Salvianolic 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.

Keywords: Components; Coronary heart disease; DanQi pill; PPARs-PGC1α pathway.

MeSH terms

  • Alkenes / pharmacology
  • Alkenes / therapeutic use
  • Animals
  • Cholesterol / biosynthesis
  • Coronary Disease / drug therapy*
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Heart / drug effects
  • Lipid Metabolism / drug effects
  • MAP Kinase Signaling System / drug effects
  • Male
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism*
  • Peroxisome Proliferator-Activated Receptors / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phytotherapy
  • Polyphenols / pharmacology
  • Polyphenols / therapeutic use
  • Proto-Oncogene Proteins c-akt / metabolism
  • Random Allocation
  • Rats, Sprague-Dawley
  • Retinoid X Receptor alpha / metabolism
  • Saponins / pharmacology
  • Saponins / therapeutic use

Substances

  • Alkenes
  • Drugs, Chinese Herbal
  • Panax notoginseng extract
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Peroxisome Proliferator-Activated Receptors
  • Polyphenols
  • Ppargc1a protein, rat
  • Retinoid X Receptor alpha
  • Saponins
  • danqi tongmai
  • salvianolic acid
  • Cholesterol
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases