Effect of DanQi Pill on PPARα, lipid disorders and arachidonic acid pathway in rat model of coronary heart disease.

Hong Chang,Tianjiao Shi,Chun Li,Wei Wang,Kuiyuan Huo,Binghua Tang,Yong Wang,Yuanyuan Wang,Qian Zhang,Guoli Wang,Qiyan Wang

doi:10.1186/s12906-016-1083-3

Abstract

BackgroundDanqi 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.Methods80 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.ResultsTwenty 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.ConclusionsDQP 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.

Highlights

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)
Effects of DQP on cardiac functions Echocardiography results showed that left ventricular end-diastolic diameter (LVEDd) and left ventricular end-systolic diameter (LVESd) in the model group increased by 53.52 % (P < 0.01) and
Effects of DQP on plasma lipid and lipoprotein levels Compared with the sham group, levels of total cholesterol (TC), TG, low density lipoprotein (LDL) and very low density lipoprotein (VLDL) in the model group increased by 40.50 % (P = 0.032), 155.33 % (P = 0.004), 49.07 % (P = 0.031) and 170.52 % (P = 0.002), respectively

Summary

Introduction

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). 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. Lipoprotein lipase (LPL) is the key enzyme in the catabolism of triglyceride It breaks down triglycerides into free fatty acids (FFA), which provide 80 % of the energy consumed by cardiomyocytes [10]. Plasma FFA are combined with fatty acid-binding protein (FABP) and transferred into cytoplasm of cardiac cells by cluster of differentiation 36 (CD36), and further transported into mitochondria through carnitine, catalyzed by carnitinepalmitoyltransferase I (CPT-I) which is another key enzyme in fatty acid metabolism [11, 12]. FFA eventually undergo oxidation in mitochondria to produce ATP for heart contraction [13, 14]

Objectives

Methods

Results

Discussion

Conclusion