title: Effect of DanQi Pill on PPARα, lipid disorders and arachidonic acid pathway in rat model of coronary heart disease.
abstract: BACKGROUND
  Danqi pill (DQP) is one of the most widely prescribed formulas and has been shown to have remarkable protective effect on coronary heart disease (CHD). However, its regulatory effects on lipid metabolism disorders haven't been comprehensively studied so far. We aimed to explore the effects of DQP on Peroxisome Proliferator activated receptors α (PPARα), lipid uptake-transportation-metabolism pathway and arachidonic acid (AA)-mediated inflammation pathway in rats with CHD.
  
  
  METHODS
  80 Sprague-Dawley (SD) Rats were randomly divided into sham group, model group, positive control group and DQP group. Rat model of CHD was induced by ligation of left ventricle anterior descending artery and fed with high fat diet in all but the sham group. Rats in sham group only underwent thoracotomy. After surgery, rats in the positive control and DQP group received daily treatments of pravastatin and DQP respectively. At 28 days after surgery, rats were sacrificed and plasma lipids were evaluated by plasma biochemical detection. Western blot and PCR were applied to evaluate the expressions of PPARα, proteins involved in lipid metabolism and AA pathways.
  
  
  RESULTS
  Twenty eight days after surgery, dyslipidemia developed in CHD model rats, as illustrated by elevated plasma lipid levels. Expressions of apolipoprotein A-I (ApoA-I), cluster of differentiation 36 (CD36) and fatty acid binding protein (FABP) in the heart tissues of model group were down-regulated compared with those in sham group. Expressions of carnitine palmitoyl transferase I (CPT-1A) and lipoproteinlipase (LPL) were also reduced significantly. In addition, levels of phospholipase A2 (PLA2) and cyclooxygenase 2 (COX-2) were up-regulated. Expressions of Nuclear factor-κB (NF- κB) and signal transducer and activator of transcription 3 (STAT3) also increased. Furthermore, Expression of PPARα decreased in the model group. DQP significantly up-regulated expressions of ApoA-I and FABP, as well as the expressions of CPT-1A and CD36. In addition, DQP down-regulated expressions of PLA2, COX-2 and NF-κB in inflammation pathway. Levels of STAT3 and LPL were not affected by DQP treatment. In particular, DQP up-regulated PPARα level significantly.
  
  
  CONCLUSIONS
  DQP could effectively regulate lipid uptake-transportation-metabolism process in CHD model rats, and the effect is achieved mainly by activating ApoA-I-CD36-CPT-1A molecules. Interestingly, DQP can up-regulate expression of PPARα significantly. The anti-inflammatory effect of DQP is partly exerted by inhibiting expressions of PLA2-COX2 -NF-κB pathway.
authors.affiliation: Beijing University of Chinese Medicine, Beijing, 100029, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chang
authors.affiliation: Beijing University of Chinese Medicine, Beijing, 100029, China.
authors.forename: Qiyan
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Beijing University of Chinese Medicine, Beijing, 100029, China.
authors.forename: Tianjiao
authors.initials: T
authors.lastname: Shi
authors.affiliation: Beijing University of Chinese Medicine, Beijing, 100029, China.
authors.forename: Kuiyuan
authors.initials: K
authors.lastname: Huo
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.affiliation: Beijing University of Chinese Medicine, Beijing, 100029, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Tangshan People's hospital, Tangshan, Hebei, 063001, China.
authors.forename: Guoli
authors.initials: G
authors.lastname: Wang
authors.affiliation: Beijing University of Chinese Medicine, Beijing, 100029, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Beijing University of Chinese Medicine, Beijing, 100029, China. binghuatang@sina.cn.
authors.forename: Binghua
authors.initials: B
authors.lastname: Tang
authors.affiliation: Beijing University of Chinese Medicine, Beijing, 100029, China. wangwei_8@sina.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Beijing University of Chinese Medicine, Beijing, 100029, China. doctor_wangyong@163.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects; D052439:Lipid Metabolism Disorders / Q000188:drug therapy* / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D047493:PPAR alpha / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004365:Drugs, Chinese Herbal; D008055:Lipids; D008074:Lipoproteins; D047493:PPAR alpha; C000605263:danqi tongmai; D016718:Arachidonic Acid
keywords: Arachidonic acid; Chinese herbs; Coronary heart disease; Lipid disorders