Danqi Pill regulates lipid metabolism disorder induced by myocardial ischemia through FATP-CPTI pathway

Wang, Yong; Li, Chun; Wang, Qiyan; Shi, Tianjiao; Wang, Jing; Chen, Hui; Wu, Yan; Han, Jing; Guo, Shuzhen; Wang, Yuanyuan; Wang, Wei

doi:10.1186/s12906-015-0548-0

Cited by 22 publications

(14 citation statements)

References 37 publications

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“…Our results showed that DQP had a remarkable cardioprotective effect, as demonstrated by improved LVEF and LVFS. Previous studies have demonstrated that DQP has cardioprotective effects, and the mechanism is related to its regulation on energy metabolism pathways [ 5 , 19 , 20 ]. DQP has also been shown to have anti-inflammatory effect in heart failure model of animals [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

Multitarget Effects of Danqi Pill on Global Gene Expression Changes in Myocardial Ischemia

Wang

Meng

Zhang

et al. 2018

International Journal of Genomics

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Danqi pill (DQP) is a widely prescribed traditional Chinese medicine (TCM) in the treatment of cardiovascular diseases. The objective of this study is to systematically characterize altered gene expression pattern induced by myocardial ischemia (MI) in a rat model and to investigate the effects of DQP on global gene expression. Global mRNA expression was measured. Differentially expressed genes among the sham group, model group, and DQP group were analyzed. The gene ontology enrichment analysis and pathway analysis of differentially expressed genes were carried out. We quantified 10,813 genes. Compared with the sham group, expressions of 339 genes were upregulated and 177 genes were downregulated in the model group. The upregulated genes were enriched in extracellular matrix organization, response to wounding, and defense response pathways. Downregulated genes were enriched in fatty acid metabolism, pyruvate metabolism, PPAR signaling pathways, and so forth. This indicated that energy metabolic disorders occurred in rats with MI. In the DQP group, expressions of genes in the altered pathways were regulated back towards normal levels. DQP reversed expression of 313 of the 516 differentially expressed genes in the model group. This study provides insight into the multitarget mechanism of TCM in the treatment of complex diseases.

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Section: Discussionmentioning

confidence: 99%

Multitarget Effects of Danqi Pill on Global Gene Expression Changes in Myocardial Ischemia

Wang

Meng

Zhang

et al. 2018

International Journal of Genomics

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“…Rats in the control group received sham operation while rats in the other groups underwent left anterior descending (LAD) artery ligation surgeries which induced models of ischemic heart disease. The operational procedures have been described in our previous studies [10, 16]. Briefly, left thoracotomies were performed after rats were anaesthetized by 1% pentobarbital sodium at the dosage of 50 mg/kg via intraperitoneal injection.…”

Section: Methodsmentioning

confidence: 99%

“…DQP could also modulate cardiac energy metabolism that has been disturbed under ischemic conditions [10]. In ischemic heart disease, overall mitochondrial oxidative catabolism decreases while reliance on anaerobic glycolysis pathways is increased [11, 12].…”

Section: Introductionmentioning

confidence: 99%

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

Wang

Zhang

et al. 2016

BMC Complement Altern Med

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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.

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“…Intriguingly, peroxisome proliferator-activated receptor gamma (PPARγ) has simultaneous regulatory effect on both glucose and lipid metabolism ( Wen et al, 2017 ). Our previous studies also suggested that PPARγ could regulate myocardial fatty acid metabolism through carnitine palmitoyltransferase 1A (CPT1A) pathways ( Wang et al, 2015 ), eventually to improve the myocardial function in HF rats.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Chinese Medicine on Lipid and Glucose Metabolism in Acute Myocardial Infarction Through PPARγ Pathway

et al. 2018

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Aim: Danqi Pill (DQP), a Chinese medicine frequently prescribed in China, has been approved to improve cardiac function by regulating cardiac energy metabolism in heart failure (HF) after acute myocardial infarction (AMI) patients. The aim of this study was to explore whether the mechanism of DQP is associated to the lipid and glucose metabolism mediated via PPARγ (peroxisome proliferator-activated receptor gamma) pathway both in vivo and in vitro.Materials and Methods: Model of HF after AMI was established with ligation of left anterior descending artery on Sprague-Dawley (SD) rats. Twenty-eight days after treatment, hematoxylin–eosin (HE) staining was applied to visualize cardiomyocyte morphological changes. High performance liquid chromatography (HPLC) was performed to assess the contents of adenosine phosphates in heart. Positron emission tomography and computed tomography (PET-CT) was conducted to evaluate the cardiac glucose metabolism. Expressions of key molecules such as PPARγ, sterol carrier protein 2 (SCP2) and long chain acyl CoA dehydrogenase (ACADL) were measured by Western blotting (WB) and immunohistochemistry (IHC). Oxygen-glucose deprivation-reperfusion (OGD/R)-induced H9C2 injury cardiomyocyte model was adopted for potential mechanism research in vitro.Results: Treatment with DQP rescued hearts from structural and functional damages as well as inflammatory infiltration. Levels of adenosine triphosphate (ATP) and energy charge (EC) in DQP group were also up-regulated compared to model group. Further results demonstrated that critical enzymes both in lipid metabolism and glucose metabolism compromised in model group compared to sham group. Intriguingly, DQP could up-regulate critical enzymes including ACADL and SCP2 in lipid metabolism accompanying with promoting effect on molecules in glycolysis simultaneously. Results on upstreaming signaling pathway demonstrated that DQP could dramatically increase the expressions of PPARγ. In vitro study suggested the efficacy of DQP could be blocked by T0070907, a selective PPARγ inhibitor.Conclusion: DQP has cardioprotective effect in improving cardiac function and energy metabolism through regulating lipid and glucose metabolism. The effects may be mediated by PPARγ pathway.

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Danqi Pill regulates lipid metabolism disorder induced by myocardial ischemia through FATP-CPTI pathway

Cited by 22 publications

References 37 publications

Multitarget Effects of Danqi Pill on Global Gene Expression Changes in Myocardial Ischemia

Multitarget Effects of Danqi Pill on Global Gene Expression Changes in Myocardial Ischemia

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

The Effect of Chinese Medicine on Lipid and Glucose Metabolism in Acute Myocardial Infarction Through PPARγ Pathway

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