基于网络药理学研究心宝丸治疗慢性心力衰竭的作用机制
|
摘要
目的探究心宝丸治疗慢性心力衰竭(CHF)的多成分、多靶点、多通路的作用机制。方法根据Cardiovascular Disease Herbal Database(CVDHD)数据库检索心宝丸中药材的有效成分,利用Cytoscape 3.6.1软件建立"成分-靶点"网络,通过Kyoto Encyclopedia of Genes and Genomes(KEGG)数据库进行筛选靶点的相关通路分析,最后利用CVDHD数据库构建心宝丸"成分-靶点-通路-疾病"网络分析心宝丸对其他疾病的潜在作用。结果预测实验表明,心宝丸中活性成分29个,作用靶点约为11个,共涉及通路24条,其中,心宝丸抗CHF的靶蛋白主要通过Cyclic Adenosine monophosphate(cAMP)信号通路、肾素分泌通路、 Cyclicguanosine monophosphate(c GMP)-Protein kinase G(PKG)信号通路、Toll样受体信号通路、Mitogen-activatedprotein kinases(MAPK)信号通路、多巴胺能突触通路、雌激素信号通路、Rap1信号通路等8条通路,调节心血管炎症过程、参与心肌重塑、增强心肌收缩力,调节心肌氧化代谢和激素水平发挥抗CHF的作用。心宝丸还对高血压、肥厚型心肌病、扩张型心肌病、Ⅱ型糖尿病、冠状动脉疾病、深静脉血栓形成等疾病具有潜在治疗作用。结论调节心血管炎症过程、参与心肌重塑、增强心肌收缩力,调节心肌氧化代谢和激素水平可能是心宝丸发挥抗CHF的作用机制之一。
Objective This study was designed to explore the multi-component, multi-target and multi-pathwaymechanisms of Xinbao Pills(XBP) in the treatment of chronic heart failure(CHF). Methods The component-targetnetwork was constructed using Cytoscape 3.6.1 software based on the active molecules of the XBP extracted from theCardiovascular Disease Herbal Database(CVDHD). The obtained targets were analyzed and screened using theKyoto Encyclopedia of Genes and Genomes(KEGG) database. A network map of component-target-pathway-disease was also constructed to analyze the potential effects of XBP on other diseases. Results It showed that 29 main active constituents of XBP and 11 relate targets involved 24 pathways,8 of which included Cyclic adenosinemonophosphate(cAMP) signaling pathway,renin secretion pathway,Cyclic guanosine monophosphate(cGMP)-Protein kinase G(PKG) signaling pathway,Toll-like receptor signaling pathway,Mitogen-activated protein kinases(MAPK) signaling pathway, dopaminergic synaptic pathway, estrogen signaling pathway and Rap1 signalingpathway. They may be closely related to the CHF involving in the regulation of cardiovascular inflammatory processes,participation in myocardial remodeling, enhancement of myocardial contractility, myocardial oxidative metabolismand hormone levels. In addition, XBP had potential therapeutic effects on hypertension, hypertrophiccardiomyopathy,dilated cardiomyopathy,type 2 diabetes,coronary artery disease,deep vein thrombosis and soforth. Conclusion Regulation of cardiovascular inflammatory process,myocardial oxidative metabolism and hormonelevels as well as participation in myocardial remodeling, enhancement of myocardial contractility may be themechanisms of XBP exerting anti-chronic heart failure effect.
Objective This study was designed to explore the multi-component, multi-target and multi-pathwaymechanisms of Xinbao Pills(XBP) in the treatment of chronic heart failure(CHF). Methods The component-targetnetwork was constructed using Cytoscape 3.6.1 software based on the active molecules of the XBP extracted from theCardiovascular Disease Herbal Database(CVDHD). The obtained targets were analyzed and screened using theKyoto Encyclopedia of Genes and Genomes(KEGG) database. A network map of component-target-pathway-disease was also constructed to analyze the potential effects of XBP on other diseases. Results It showed that 29 main active constituents of XBP and 11 relate targets involved 24 pathways,8 of which included Cyclic adenosinemonophosphate(cAMP) signaling pathway,renin secretion pathway,Cyclic guanosine monophosphate(cGMP)-Protein kinase G(PKG) signaling pathway,Toll-like receptor signaling pathway,Mitogen-activated protein kinases(MAPK) signaling pathway, dopaminergic synaptic pathway, estrogen signaling pathway and Rap1 signalingpathway. They may be closely related to the CHF involving in the regulation of cardiovascular inflammatory processes,participation in myocardial remodeling, enhancement of myocardial contractility, myocardial oxidative metabolismand hormone levels. In addition, XBP had potential therapeutic effects on hypertension, hypertrophiccardiomyopathy,dilated cardiomyopathy,type 2 diabetes,coronary artery disease,deep vein thrombosis and soforth. Conclusion Regulation of cardiovascular inflammatory process,myocardial oxidative metabolism and hormonelevels as well as participation in myocardial remodeling, enhancement of myocardial contractility may be themechanisms of XBP exerting anti-chronic heart failure effect.
引文
[1] SR P, IL P. From acute decompensated to chronic heart failure[J].Am J Cardiol,2014,12(114):1923-1929.
[2] LAM C S P, DONAL E, KRAIGHER-KRAINER E, et al.Epidemiology and clinical course of heart failure with preserved ejection fraction[J]. European Journal of Heart Failure, 2011, 13(1):18-28.
[3]彭广操,朱明军,王永霞,等.心宝丸治疗病态窦房结综合征的系统评价[J].中国实验方剂学杂志,2012,18(7):286-288.
[4] ZHANG G,LI Q,CHEN Q,et al. Network pharmacology:a new approach for chinese herbal medicine research[J]. Evidence-Based Complementary and Alternative Medicine,2013,2013:1-9.
[5]王冬梅,古江勇,朱伟,等.古方“四物汤”治疗银屑病计算机网络药理学研究[J].计算机与应用化学,2013,30(3):236-240.
[6]李梢.网络靶标:中药方剂网络药理学研究的一个切入点[J].中国中药杂志,2011,36(15):2017-2020.
[7]袁荣高,顾明华,古江勇.基于网络药理学研究大川芎方治疗偏头痛的作用机制[J].南京中医药大学学报,2016,32(6):571-576.
[8]王巍,苏光悦,胡婉琦,等.近10年人参皂苷对心血管疾病的药理作用研究进展[J].中草药,2016,47(20):3736-3741.
[9]高艳荣,张莉,张磊.蟾酥及其有效成分的药理作用及机制研究进展[J].武警医学院学报,2003,12(5):406-408.
[10]周华春.洋金花的药理作用及临床应用研究[J].中医临床研究,2017,9(9):129-130.
[11] HARTMANN R W, MüLLER U, EHMER P B. Discovery of selective CYP11B2(aldosterone synthase)inhibitors for the therapy of congestive heart failure and myocardial fibrosis[J]. European Journal of Medicinal Chemistry,2003,38(4):363-366.
[12] OTTE C WüST S,ZHAO S,et al. Glucocorticoid receptor gene,low-grade inflammation,and heart failure:the heart and soul study[J]. J Clin Endocrinol Metab,2010,95(6):2885-2891.
[13] MISSALE C, LOMBARDI C, DE C R, et al. Dopaminergic receptor mechanisms modulating the renin-angiotensin system and aldosterone secretion:an overview[J]. J Cardiovasc Pharmacol,1989,14(6):S29-S39.
[14] ARIAS T, BEAUMONT J, LóPEZ B, et al. Association of the peroxisome proliferator-activated receptorαgene L162V polymorphism with stage C heart failure[J]. Journal of Hypertension,2011,29(5):876-883.
[15] K?L??K?RAN AB, B0, KARADAG?B, et al. Renin-angiotensin system blockade in the treatment of heart failure and the role of valsartan in this treatment[J]. Anadolu kardiyoloji dergisi:AKD=the Anatolian journal of cardiology,2014,14 Suppl 2(2):S1.
[16] MéTRICH M, BERTHOUZE M, MOREL E, et al.Role of the cAMP-binding protein Epac in cardiovascular physiology and pathophysiology[J]. Pflügers Archiv European Journal of Physiology,2010,459(4):535.
[17] TORP-PEDERSEN C, KOBER L, CARLSEN JE, et al. A randomised trial of a pre-synaptic stimulator of DA2-dopaminergic andα2-adrenergic receptors on morbidity and mortality in patients with heart failure[J]. European Journal of Heart Failure, 2008, 10(1):89-95.
[18] REHMANN H. Epac-inhibitors:facts and artefacts[J]. Sci Rep,2013,3(10):3032.
[19] CHEN M,DOHERTY S D,HSU S. Innovative uses of thalidomide[J]. Dermatologic Clinics,2010,28(3):577.
[20]张艳,李帅.心宝丸治疗冠心病合并房颤伴长RR间期疗效观察[J].淮海医药,2016,34(3):338-339.
[2] LAM C S P, DONAL E, KRAIGHER-KRAINER E, et al.Epidemiology and clinical course of heart failure with preserved ejection fraction[J]. European Journal of Heart Failure, 2011, 13(1):18-28.
[3]彭广操,朱明军,王永霞,等.心宝丸治疗病态窦房结综合征的系统评价[J].中国实验方剂学杂志,2012,18(7):286-288.
[4] ZHANG G,LI Q,CHEN Q,et al. Network pharmacology:a new approach for chinese herbal medicine research[J]. Evidence-Based Complementary and Alternative Medicine,2013,2013:1-9.
[5]王冬梅,古江勇,朱伟,等.古方“四物汤”治疗银屑病计算机网络药理学研究[J].计算机与应用化学,2013,30(3):236-240.
[6]李梢.网络靶标:中药方剂网络药理学研究的一个切入点[J].中国中药杂志,2011,36(15):2017-2020.
[7]袁荣高,顾明华,古江勇.基于网络药理学研究大川芎方治疗偏头痛的作用机制[J].南京中医药大学学报,2016,32(6):571-576.
[8]王巍,苏光悦,胡婉琦,等.近10年人参皂苷对心血管疾病的药理作用研究进展[J].中草药,2016,47(20):3736-3741.
[9]高艳荣,张莉,张磊.蟾酥及其有效成分的药理作用及机制研究进展[J].武警医学院学报,2003,12(5):406-408.
[10]周华春.洋金花的药理作用及临床应用研究[J].中医临床研究,2017,9(9):129-130.
[11] HARTMANN R W, MüLLER U, EHMER P B. Discovery of selective CYP11B2(aldosterone synthase)inhibitors for the therapy of congestive heart failure and myocardial fibrosis[J]. European Journal of Medicinal Chemistry,2003,38(4):363-366.
[12] OTTE C WüST S,ZHAO S,et al. Glucocorticoid receptor gene,low-grade inflammation,and heart failure:the heart and soul study[J]. J Clin Endocrinol Metab,2010,95(6):2885-2891.
[13] MISSALE C, LOMBARDI C, DE C R, et al. Dopaminergic receptor mechanisms modulating the renin-angiotensin system and aldosterone secretion:an overview[J]. J Cardiovasc Pharmacol,1989,14(6):S29-S39.
[14] ARIAS T, BEAUMONT J, LóPEZ B, et al. Association of the peroxisome proliferator-activated receptorαgene L162V polymorphism with stage C heart failure[J]. Journal of Hypertension,2011,29(5):876-883.
[15] K?L??K?RAN AB, B0, KARADAG?B, et al. Renin-angiotensin system blockade in the treatment of heart failure and the role of valsartan in this treatment[J]. Anadolu kardiyoloji dergisi:AKD=the Anatolian journal of cardiology,2014,14 Suppl 2(2):S1.
[16] MéTRICH M, BERTHOUZE M, MOREL E, et al.Role of the cAMP-binding protein Epac in cardiovascular physiology and pathophysiology[J]. Pflügers Archiv European Journal of Physiology,2010,459(4):535.
[17] TORP-PEDERSEN C, KOBER L, CARLSEN JE, et al. A randomised trial of a pre-synaptic stimulator of DA2-dopaminergic andα2-adrenergic receptors on morbidity and mortality in patients with heart failure[J]. European Journal of Heart Failure, 2008, 10(1):89-95.
[18] REHMANN H. Epac-inhibitors:facts and artefacts[J]. Sci Rep,2013,3(10):3032.
[19] CHEN M,DOHERTY S D,HSU S. Innovative uses of thalidomide[J]. Dermatologic Clinics,2010,28(3):577.
[20]张艳,李帅.心宝丸治疗冠心病合并房颤伴长RR间期疗效观察[J].淮海医药,2016,34(3):338-339.