Skip to main content
Top
Published in: BMC Complementary Medicine and Therapies 1/2016

Open Access 01-12-2016 | Research article

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

Authors: Qiyan Wang, Chun Li, Qian Zhang, Yuanyuan Wang, Tianjiao Shi, Linghui Lu, Yi Zhang, Yong Wang, Wei Wang

Published in: BMC Complementary Medicine and Therapies | Issue 1/2016

Login to get access

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.
Literature
1.
go back to reference Go AS, et al. Executive summary: heart disease and stroke statistics--2014 update: a report from the American Heart Association. Circulation. 2014;129(3):399–410.CrossRefPubMed Go AS, et al. Executive summary: heart disease and stroke statistics--2014 update: a report from the American Heart Association. Circulation. 2014;129(3):399–410.CrossRefPubMed
2.
go back to reference Wong MC, Zhang De X, Wang HH. Rapid emergence of atherosclerosis in Asia: a systematic review of coronary atherosclerotic heart disease epidemiology and implications for prevention and control strategies. Curr Opin Lipidol. 2015;26(4):257–69.CrossRefPubMed Wong MC, Zhang De X, Wang HH. Rapid emergence of atherosclerosis in Asia: a systematic review of coronary atherosclerotic heart disease epidemiology and implications for prevention and control strategies. Curr Opin Lipidol. 2015;26(4):257–69.CrossRefPubMed
3.
go back to reference LaRosa JC. Prevention and treatment of coronary heart disease: who benefits? Circulation. 2001;104(14):1688–92.CrossRefPubMed LaRosa JC. Prevention and treatment of coronary heart disease: who benefits? Circulation. 2001;104(14):1688–92.CrossRefPubMed
4.
go back to reference Sheridan S L,et al. A randomized trial of an intervention to improve use and adherence to effective coronary heart disease prevention strategies.BMC Health Services Research. 2011;11(1):1–10. Sheridan S L,et al. A randomized trial of an intervention to improve use and adherence to effective coronary heart disease prevention strategies.BMC Health Services Research. 2011;11(1):1–10.
5.
go back to reference Wang Y, et al. DanQi Pill protects against heart failure through the arachidonic acid metabolism pathway by attenuating different cyclooxygenases and leukotrienes B4. BMC Complement Altern Med. 2014;14:67.CrossRefPubMedPubMedCentral Wang Y, et al. DanQi Pill protects against heart failure through the arachidonic acid metabolism pathway by attenuating different cyclooxygenases and leukotrienes B4. BMC Complement Altern Med. 2014;14:67.CrossRefPubMedPubMedCentral
7.
go back to reference Chen J, et al. Separation and identification of water-soluble salvianolic acids from Salvia miltiorrhiza Bunge by high-speed counter-current chromatography and ESI-MS analysis. Talanta. 2006;69(1):172–9.CrossRefPubMed Chen J, et al. Separation and identification of water-soluble salvianolic acids from Salvia miltiorrhiza Bunge by high-speed counter-current chromatography and ESI-MS analysis. Talanta. 2006;69(1):172–9.CrossRefPubMed
8.
go back to reference Liu P, et al. A rapid method for chemical fingerprint analysis of Pan Panax notoginseng powders by ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Chin J Nat Med. 2015;13(6):471–80.PubMed Liu P, et al. A rapid method for chemical fingerprint analysis of Pan Panax notoginseng powders by ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Chin J Nat Med. 2015;13(6):471–80.PubMed
9.
go back to reference Yao CL, et al. Simultaneous quantitation of five Panax notoginseng saponins by multi heart-cutting two-dimensional liquid chromatography: Method development and application to the quality control of eight Notoginseng containing Chinese patent medicines. J Chromatogr A. 2015;1402:71–81.CrossRefPubMed Yao CL, et al. Simultaneous quantitation of five Panax notoginseng saponins by multi heart-cutting two-dimensional liquid chromatography: Method development and application to the quality control of eight Notoginseng containing Chinese patent medicines. J Chromatogr A. 2015;1402:71–81.CrossRefPubMed
10.
go back to reference Wang Y, et al. Danqi Pill regulates lipid metabolism disorder induced by myocardial ischemia through FATP-CPTI pathway. BMC Complement Altern Med. 2015;15:28.CrossRefPubMedPubMedCentral Wang Y, et al. Danqi Pill regulates lipid metabolism disorder induced by myocardial ischemia through FATP-CPTI pathway. BMC Complement Altern Med. 2015;15:28.CrossRefPubMedPubMedCentral
11.
go back to reference van der Vusse GJ, van Bilsen M, Glatz JF. Cardiac fatty acid uptake and transport in health and disease. Cardiovasc Res. 2000;45(2):279–93.CrossRefPubMed van der Vusse GJ, van Bilsen M, Glatz JF. Cardiac fatty acid uptake and transport in health and disease. Cardiovasc Res. 2000;45(2):279–93.CrossRefPubMed
12.
go back to reference Finck BN. The PPAR regulatory system in cardiac physiology and disease. Cardiovasc Res. 2007;73(2):269–77.CrossRefPubMed Finck BN. The PPAR regulatory system in cardiac physiology and disease. Cardiovasc Res. 2007;73(2):269–77.CrossRefPubMed
13.
go back to reference Gilde AJ, et al. Peroxisome proliferator-activated receptor (PPAR) alpha and PPARbeta/delta, but not PPARgamma, modulate the expression of genes involved in cardiac lipid metabolism. Circ Res. 2003;92(5):518–24.CrossRefPubMed Gilde AJ, et al. Peroxisome proliferator-activated receptor (PPAR) alpha and PPARbeta/delta, but not PPARgamma, modulate the expression of genes involved in cardiac lipid metabolism. Circ Res. 2003;92(5):518–24.CrossRefPubMed
14.
go back to reference Djouadi F, et al. The role of the peroxisome proliferator-activated receptor alpha (PPAR alpha) in the control of cardiac lipid metabolism. Prostaglandins Leukot Essent Fatty Acids. 1999;60(5-6):339–43.CrossRefPubMed Djouadi F, et al. The role of the peroxisome proliferator-activated receptor alpha (PPAR alpha) in the control of cardiac lipid metabolism. Prostaglandins Leukot Essent Fatty Acids. 1999;60(5-6):339–43.CrossRefPubMed
15.
go back to reference Lehman JJ, et al. Peroxisome proliferator-activated receptor gamma coactivator-1 promotes cardiac mitochondrial biogenesis. J Clin Invest. 2000;106(7):847–56.CrossRefPubMedPubMedCentral Lehman JJ, et al. Peroxisome proliferator-activated receptor gamma coactivator-1 promotes cardiac mitochondrial biogenesis. J Clin Invest. 2000;106(7):847–56.CrossRefPubMedPubMedCentral
16.
go back to reference Wang J, et al. Mechanism of QSYQ on anti-apoptosis mediated by different subtypes of cyclooxygenase in AMI induced heart failure rats. BMC Complement Altern Med. 2015;15:352.CrossRefPubMedPubMedCentral Wang J, et al. Mechanism of QSYQ on anti-apoptosis mediated by different subtypes of cyclooxygenase in AMI induced heart failure rats. BMC Complement Altern Med. 2015;15:352.CrossRefPubMedPubMedCentral
17.
go back to reference Alexander ET, et al. Influence of apolipoprotein A-I domain structure on macrophage reverse cholesterol transport in mice. Arterioscler Thromb Vasc Biol. 2011;31(2):320–7.CrossRefPubMed Alexander ET, et al. Influence of apolipoprotein A-I domain structure on macrophage reverse cholesterol transport in mice. Arterioscler Thromb Vasc Biol. 2011;31(2):320–7.CrossRefPubMed
18.
go back to reference Obunike JC, et al. Cellular differences in lipoprotein lipase-mediated uptake of low density lipoproteins. J Biol Chem. 1994;269(18):13129–35.PubMed Obunike JC, et al. Cellular differences in lipoprotein lipase-mediated uptake of low density lipoproteins. J Biol Chem. 1994;269(18):13129–35.PubMed
19.
go back to reference Medina MW. The relationship between HMGCR genetic variation, alternative splicing, and statin efficacy. Discov Med. 2010;9(49):495–9.PubMed Medina MW. The relationship between HMGCR genetic variation, alternative splicing, and statin efficacy. Discov Med. 2010;9(49):495–9.PubMed
20.
go back to reference Schmidt K, et al. Cholesterol metabolism: the main pathway acting downstream of cytochrome P450 oxidoreductase in skeletal development of the limb. Mol Cell Biol. 2009;29(10):2716–29.CrossRefPubMedPubMedCentral Schmidt K, et al. Cholesterol metabolism: the main pathway acting downstream of cytochrome P450 oxidoreductase in skeletal development of the limb. Mol Cell Biol. 2009;29(10):2716–29.CrossRefPubMedPubMedCentral
21.
go back to reference Barger PM, Kelly DP. PPAR signaling in the control of cardiac energy metabolism. Trends Cardiovasc Med. 2000;10(6):238–45.CrossRefPubMed Barger PM, Kelly DP. PPAR signaling in the control of cardiac energy metabolism. Trends Cardiovasc Med. 2000;10(6):238–45.CrossRefPubMed
22.
go back to reference Madrazo JA, Kelly DP. The PPAR trio: regulators of myocardial energy metabolism in health and disease. J Mol Cell Cardiol. 2008;44(6):968–75.CrossRefPubMed Madrazo JA, Kelly DP. The PPAR trio: regulators of myocardial energy metabolism in health and disease. J Mol Cell Cardiol. 2008;44(6):968–75.CrossRefPubMed
23.
go back to reference Garcia-Rojas P, et al. Induction of peroxisomal proliferator-activated receptor gamma and peroxisomal proliferator-activated receptor gamma coactivator 1 by unsaturated fatty acids, retinoic acid, and carotenoids in preadipocytes obtained from bovine white adipose tissue1,2. J Anim Sci. 2010;88(5):1801–8.CrossRefPubMed Garcia-Rojas P, et al. Induction of peroxisomal proliferator-activated receptor gamma and peroxisomal proliferator-activated receptor gamma coactivator 1 by unsaturated fatty acids, retinoic acid, and carotenoids in preadipocytes obtained from bovine white adipose tissue1,2. J Anim Sci. 2010;88(5):1801–8.CrossRefPubMed
24.
go back to reference Duncan JG, Finck BN. The PPARalpha-PGC-1alpha Axis Controls Cardiac Energy Metabolism in Healthy and Diseased Myocardium. PPAR Res. 2008;2008:253817.CrossRefPubMed Duncan JG, Finck BN. The PPARalpha-PGC-1alpha Axis Controls Cardiac Energy Metabolism in Healthy and Diseased Myocardium. PPAR Res. 2008;2008:253817.CrossRefPubMed
25.
go back to reference Liang H, Ward WF. PGC-1alpha: a key regulator of energy metabolism. Adv Physiol Educ. 2006;30(4):145–51.CrossRefPubMed Liang H, Ward WF. PGC-1alpha: a key regulator of energy metabolism. Adv Physiol Educ. 2006;30(4):145–51.CrossRefPubMed
26.
go back to reference Hu Y, et al. Cardioprotection induced by hydrogen sulfide preconditioning involves activation of ERK and PI3K/Akt pathways. Pflugers Arch. 2008;455(4):607–16.CrossRefPubMed Hu Y, et al. Cardioprotection induced by hydrogen sulfide preconditioning involves activation of ERK and PI3K/Akt pathways. Pflugers Arch. 2008;455(4):607–16.CrossRefPubMed
27.
go back to reference Gordon T, et al. High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med. 1977;62(5):707–14.CrossRefPubMed Gordon T, et al. High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med. 1977;62(5):707–14.CrossRefPubMed
28.
go back to reference Di Angelantonio E, et al. Major lipids, apolipoproteins, and risk of vascular disease. JAMA. 2009;302(18):1993–2000.CrossRefPubMed Di Angelantonio E, et al. Major lipids, apolipoproteins, and risk of vascular disease. JAMA. 2009;302(18):1993–2000.CrossRefPubMed
29.
go back to reference Navab M, et al. HDL and cardiovascular disease: atherogenic and atheroprotective mechanisms. Nat Rev Cardiol. 2011;8(4):222–32.CrossRefPubMed Navab M, et al. HDL and cardiovascular disease: atherogenic and atheroprotective mechanisms. Nat Rev Cardiol. 2011;8(4):222–32.CrossRefPubMed
30.
go back to reference Shao B. Site-specific oxidation of apolipoprotein A-I impairs cholesterol export by ABCA1, a key cardioprotective function of HDL. Biochim Biophys Acta. 2012;1821(3):490–501.CrossRefPubMed Shao B. Site-specific oxidation of apolipoprotein A-I impairs cholesterol export by ABCA1, a key cardioprotective function of HDL. Biochim Biophys Acta. 2012;1821(3):490–501.CrossRefPubMed
31.
go back to reference Smith BK, et al. FAT/CD36 is located on the outer mitochondrial membrane, upstream of long-chain acyl-CoA synthetase, and regulates palmitate oxidation. Biochem J. 2011;437(1):125–34.CrossRefPubMed Smith BK, et al. FAT/CD36 is located on the outer mitochondrial membrane, upstream of long-chain acyl-CoA synthetase, and regulates palmitate oxidation. Biochem J. 2011;437(1):125–34.CrossRefPubMed
32.
go back to reference He J, et al. The emerging roles of fatty acid translocase/CD36 and the aryl hydrocarbon receptor in fatty liver disease. Exp Biol Med (Maywood). 2011;236(10):1116–21.CrossRef He J, et al. The emerging roles of fatty acid translocase/CD36 and the aryl hydrocarbon receptor in fatty liver disease. Exp Biol Med (Maywood). 2011;236(10):1116–21.CrossRef
33.
go back to reference Bruce CR, et al. Overexpression of carnitine palmitoyltransferase-1 in skeletal muscle is sufficient to enhance fatty acid oxidation and improve high-fat diet-induced insulin resistance. Diabetes. 2009;58(3):550–8.CrossRefPubMedPubMedCentral Bruce CR, et al. Overexpression of carnitine palmitoyltransferase-1 in skeletal muscle is sufficient to enhance fatty acid oxidation and improve high-fat diet-induced insulin resistance. Diabetes. 2009;58(3):550–8.CrossRefPubMedPubMedCentral
34.
go back to reference Herrmann T, et al. Mouse fatty acid transport protein 4 (FATP4): characterization of the gene and functional assessment as a very long chain acyl-CoA synthetase. Gene. 2001;270(1-2):31–40.CrossRefPubMed Herrmann T, et al. Mouse fatty acid transport protein 4 (FATP4): characterization of the gene and functional assessment as a very long chain acyl-CoA synthetase. Gene. 2001;270(1-2):31–40.CrossRefPubMed
35.
go back to reference Hall AM, et al. Enzymatic properties of purified murine fatty acid transport protein 4 and analysis of acyl-CoA synthetase activities in tissues from FATP4 null mice. J Biol Chem. 2005;280(12):11948–54.CrossRefPubMed Hall AM, et al. Enzymatic properties of purified murine fatty acid transport protein 4 and analysis of acyl-CoA synthetase activities in tissues from FATP4 null mice. J Biol Chem. 2005;280(12):11948–54.CrossRefPubMed
36.
go back to reference Balakumar P, Kathuria S. Submaximal PPARgamma activation and endothelial dysfunction: new perspectives for the management of cardiovascular disorders. Br J Pharmacol. 2012;166(7):1981–92.CrossRefPubMedPubMedCentral Balakumar P, Kathuria S. Submaximal PPARgamma activation and endothelial dysfunction: new perspectives for the management of cardiovascular disorders. Br J Pharmacol. 2012;166(7):1981–92.CrossRefPubMedPubMedCentral
37.
go back to reference Huss JM, et al. Estrogen-related receptor alpha directs peroxisome proliferator-activated receptor alpha signaling in the transcriptional control of energy metabolism in cardiac and skeletal muscle. Mol Cell Biol. 2004;24(20):9079–91.CrossRefPubMedPubMedCentral Huss JM, et al. Estrogen-related receptor alpha directs peroxisome proliferator-activated receptor alpha signaling in the transcriptional control of energy metabolism in cardiac and skeletal muscle. Mol Cell Biol. 2004;24(20):9079–91.CrossRefPubMedPubMedCentral
38.
go back to reference Garnier A, et al. Depressed mitochondrial transcription factors and oxidative capacity in rat failing cardiac and skeletal muscles. J Physiol. 2003;551(Pt 2):491–501.CrossRefPubMedPubMedCentral Garnier A, et al. Depressed mitochondrial transcription factors and oxidative capacity in rat failing cardiac and skeletal muscles. J Physiol. 2003;551(Pt 2):491–501.CrossRefPubMedPubMedCentral
39.
go back to reference Sack MN, Kelly DP. The energy substrate switch during development of heart failure: gene regulatory mechanisms (Review). Int J Mol Med. 1998;1(1):17–24.PubMed Sack MN, Kelly DP. The energy substrate switch during development of heart failure: gene regulatory mechanisms (Review). Int J Mol Med. 1998;1(1):17–24.PubMed
40.
go back to reference Sambandam N, et al. Chronic activation of PPARalpha is detrimental to cardiac recovery after ischemia. Am J Physiol Heart Circ Physiol. 2006;290(1):H87–95.CrossRefPubMed Sambandam N, et al. Chronic activation of PPARalpha is detrimental to cardiac recovery after ischemia. Am J Physiol Heart Circ Physiol. 2006;290(1):H87–95.CrossRefPubMed
41.
go back to reference Lygate CA, et al. The PPARgamma-activator rosiglitazone does not alter remodeling but increases mortality in rats post-myocardial infarction. Cardiovasc Res. 2003;58(3):632–7.CrossRefPubMed Lygate CA, et al. The PPARgamma-activator rosiglitazone does not alter remodeling but increases mortality in rats post-myocardial infarction. Cardiovasc Res. 2003;58(3):632–7.CrossRefPubMed
42.
go back to reference Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007;356(24):2457–71.CrossRefPubMed Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007;356(24):2457–71.CrossRefPubMed
43.
go back to reference Venkataramanan R, Komoroski B, Strom S. In vitro and in vivo assessment of herb drug interactions. Life Sci. 2006;78(18):2105–15.CrossRefPubMed Venkataramanan R, Komoroski B, Strom S. In vitro and in vivo assessment of herb drug interactions. Life Sci. 2006;78(18):2105–15.CrossRefPubMed
44.
go back to reference Blanes MG, et al. Phosphorylation of tyrosine 801 of vascular endothelial growth factor receptor-2 is necessary for Akt-dependent endothelial nitric-oxide synthase activation and nitric oxide release from endothelial cells. J Biol Chem. 2007;282(14):10660–9.CrossRefPubMed Blanes MG, et al. Phosphorylation of tyrosine 801 of vascular endothelial growth factor receptor-2 is necessary for Akt-dependent endothelial nitric-oxide synthase activation and nitric oxide release from endothelial cells. J Biol Chem. 2007;282(14):10660–9.CrossRefPubMed
45.
go back to reference O'Neill BT, et al. A conserved role for phosphatidylinositol 3-kinase but not Akt signaling in mitochondrial adaptations that accompany physiological cardiac hypertrophy. Cell Metab. 2007;6(4):294–306.CrossRefPubMedPubMedCentral O'Neill BT, et al. A conserved role for phosphatidylinositol 3-kinase but not Akt signaling in mitochondrial adaptations that accompany physiological cardiac hypertrophy. Cell Metab. 2007;6(4):294–306.CrossRefPubMedPubMedCentral
46.
go back to reference Hausenloy DJ, et al. Ischemic preconditioning protects by activating prosurvival kinases at reperfusion. Am J Physiol Heart Circ Physiol. 2005;288(2):H971–6.CrossRefPubMed Hausenloy DJ, et al. Ischemic preconditioning protects by activating prosurvival kinases at reperfusion. Am J Physiol Heart Circ Physiol. 2005;288(2):H971–6.CrossRefPubMed
47.
go back to reference Yue TL, et al. Inhibition of extracellular signal-regulated kinase enhances Ischemia/Reoxygenation-induced apoptosis in cultured cardiac myocytes and exaggerates reperfusion injury in isolated perfused heart. Circ Res. 2000;86(6):692–9.CrossRefPubMed Yue TL, et al. Inhibition of extracellular signal-regulated kinase enhances Ischemia/Reoxygenation-induced apoptosis in cultured cardiac myocytes and exaggerates reperfusion injury in isolated perfused heart. Circ Res. 2000;86(6):692–9.CrossRefPubMed
Metadata
Title
The effect of Chinese herbs and its effective components on coronary heart disease through PPARs-PGC1α pathway
Authors
Qiyan Wang
Chun Li
Qian Zhang
Yuanyuan Wang
Tianjiao Shi
Linghui Lu
Yi Zhang
Yong Wang
Wei Wang
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2016
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-016-1496-z

Other articles of this Issue 1/2016

BMC Complementary Medicine and Therapies 1/2016 Go to the issue