Abstract��OBJECTIVE To construct a network of active components-effect target of xiangdan injection and the network of protein interaction,to analyze the functions and pathways involved in the targets,and to investigate its mechanism of multicomponent-multitarget-multipathway in the treatment of coronary heart disease. METHODS The main active components in xiangdan injection, such as danshensu, salvianolic acid A, salvianolic acid B, salvianolic acid D, tanshinone ��A, protocatechuic aldehyde,rosmarinic acid,and oxidated nerolidol were used as the research object to predict targets of active components in xiangdan injection on the basis of reverse docking server (PharmMapper),to screen the targets for the treatment of coronary heart disease through the human genome annotation database (GeneCards), to construct active ingredients-target disease network using Cytoscape 3.5.1 software, to construct target protein protein interaction(PPI) network using STRING platform,and to analyze the target GO biological process and KEGG metabolic pathway using biological information annotation database (DAVID). RESULTS Eight pharmacodynamic components of xiangdan injection act on ACE, HSP90AA1, AKT1, NOS3, F2, F7 and other 257 potential targets for coronary heart disease,which mainly related to the 13 signaling pathways and 12 biological processes. CONCLUSION The main active ingredient of xiangdan injection could treat the coronary heart disease by PPAR, complement and coagulation cascades, HIF-1, estrogen signaling pathway, play a role of anti-inflammatory, anticoagulant, anti-hypoxia, anti-apoptosis and regulating hormones.
��Ծ��, ��־ǿ, ��Խ, �´���, ������. �㵤ע��Һ���ƹ��IJ���Ҫ���Գɷ�-�е�-ͨ·���������[J]. �й�ҩѧ��־, 2018, 53(22): 1927-1935.
LI Yue-wen, LIU Zhi-qiang, ZHAO Yue, CHEN Chun-lin, WANG Bo-long. Network Analysis of Main Active Ingredients-Target-Pathway of Xiangdan Injection in Treatment of Coronary Heart Disease. Chinese Pharmaceutical Journal, 2018, 53(22): 1927-1935.
LU Q, SHAO Q, QU H B, et al. Determination of water-soluble ingredients in xiangdan injection and nerolidol content with column switching chromatography at same time [J]. China J Chin Mater Med(�й���ҩ��־),2008,33(23):2776-2780.
[2]
YU J J, XU F H. Determination of sodium danshensu, protocatechuic aldehyde and salvianolic acid b in xiangdan injection by RP-HPLC[J]. Strait Pharm J(��Ͽҩѧ),2012,24(2):45-47.
[3]
WU D,WANG X. Study on the determination of the content of effective components in xiangdan injection[J]. Heilongjiang Sci Tech Inform(�������Ƽ���Ϣ),2017(16):28.
[4]
WANG B Y,WU X Y,FAN G W. Pharmacologic mechanism for protective effects of danshensu on cardiovascular system[J]. China Tradit Herb Drugs(�в�ҩ),2014,45(17):2571-2575.
[5]
QI T T, BAO Y M, LIU A H. Research advances in protective effect of water-soluble ingredients in Salviae Miltiorrhizae Radix et Rhizoma on myocardial ischemia and reperfusion injury[J]. Chin J Exp Tradit Med Form(�й�ʵ�鷽��ѧ��־),2017,23(24):217-223.
[6]
ZHU W T, FAN X M, WEI H, et al. Mechanism research of apatinib-treated breast cancer based on network pharmacology[J]. Chin Pharm J(�й�ҩѧ��־),2016,51(18):1569-1573.
[7]
ZHAO Q Q, LI X, CENG M L, et al. A network pharmacology based study of regulation effects of the main active components in honghua injection on cerebrovascular disease network[J]. Chin Pharm J(�й�ҩѧ��־),2015,50(16):1402-1407.
[8]
LI J, GAO L, GAO Y, et al. Exploration in targets action of antitussive and expectorant bioactive components from Farfarae Flos based on network pharmacology[J]. China Tradit Herb Drugs(�в�ҩ),2018,49(1):179-187.
[9]
CHEN S. Chemoinformatics-based on screening and mechanism investigation of heart failure related drugs[D]. Shanghai:The Second Military Medical University,2017.
[10]
LU Q, SHAO Y L. Research status of determination of effective constituents of Xiangdan injection[J]. Zhejiang J Integr Tradit Chin West Med(�㽭����ҽ�����־),2012,22(9):743-746.
[11]
LIN R,DUAN J L,MOU F, et al. Progress in research of the metabolic pathways and metabolites of major active constituents of Salvia miltiorrhiza[J]. Chin New Drugs J(�й���ҩ��־),2017,26(19):2271-2277.
[12]
LEE H J, SEO M, LEE E J.Salvianolic acid b inhibits atherogenesis of vascular cells through induction of Nrf2-dependent Heme oxygenase-1[J]. Curr Med Chem,2014,21(26) : 3095-3106.
[13]
LIN C,LIU Z G,QIAN X, et al. Research progress of salvianolic acid B in cardiovascular diseases[J]. Chin Pharmacol Bull(�й�ҩ��ѧͨ��),2015,31(4):449-452.
[14]
LIU L S,WANG C T,WANG L M, et al. Effect of salveanolic acid B on the release of VEGF, SDF-1, IL-8 and MMP9 cytokines and adhesion ability of EPCs[J]. Pract Pharm Clin Remed(ʵ��ҩ�����ٴ�),2018,21(1):5-9.
[15]
SHEN W L,YU F,XU L, et al. Protective effects of tanshinone ��A derivative on myocardial ischemia/reperfusion injury in rats[J]. J Chin Pharm Sci,2018,27(1):1-13.
[16]
LIU H Y,FAN M M,HE M Z, et al. Advances in studies on volatile oil from Lignum Dalbergiane Odoriferae[J]. China Tradit Herb Drugs(�в�ҩ),2009,40(11):1847-1849.
[17]
LIU X Y,YANG J W,PENG W J, et al. Role of HSP90 in focal cerebral ischemia/reperfusion injury through protein kinase B pathway[J]. Chin J Geriatr Heart Brain Vessel Dis(�л���������Ѫ�ܲ���־),2017,19(12):1316-1319.
[18]
TIAN J P. Bioinformatics forecast on the molecular mechanisms for the treatment of coronary heart disease by the common drug pairs invigorating qi,promoting blood circulation and blood-breaking drugs[D]. Guangzhou:Guangzhou University of Chinese Medicine,2013.
[19]
LIU X. Study on estrogen like protective effect of tanshinone ��A on vascular endothelial injury and its mechanism[D]. Beijing:Beijing University of Chinese Medicine,2013.
[20]
LI L,CAI H Y,GUO T, et al. Signal transduction by vascular endothelial growth factor receptors[J]. Adv Cardiovas Dis(��Ѫ�ܲ�ѧ��չ),2015,36(2):210-213.
[21]
MA J,GUO C X,LU P P, et al. Cardioprotective efficacy of qishen capsule in rats with chronic myocardial infarction[J]. Chin Pharm J(�й�ҩѧ��־),2017,52(13):1137-1146.
[22]
XIANG B X,LIU T T,SUN F L, et al. Advances in research on VEGF-related signaling pathways in angiogenesis[J]. Chin Compar Med(�й��Ƚ�ҽѧ��־),2015,25(12):81-86.
[23]
PAN Y,YIN J,CAI X M, et al. Research progress on intervention of traditional Chinese medicine on coronary heart disease through PI3K/Akt signaling pathway[J]. China Tradit Herb Drugs(�в�ҩ),2017,48(19):4100-4104.
[24]
YUAN X.Pharmacological postconditioning with tanshinone ��A attenuate myocardial ischemia-reperfusion injury through PI3K/AKt pathway in rats[D]. Fuzhou:Fujian Medical University,2013.
[25]
DAI J, JIANG D N,MAO W, et al. Effects of Tanyu tongzhi granule on TCM syndrome and PPAR�� of coronary heart disease[J]. China J Tradit Chin Med (�л���ҽҩ��־),2010,25(7):1112-1114.
[26]
TAN C B,SHI L L,ZHOU Z X, et al. Progress in research and development of peroxisome proliferator activated receptor-gamma related drugs[J]. Chin Pharm J(�й�ҩѧ��־),2013,48(6):406-409.
[27]
SUN A,LIU H,WANG S, et al. Salvianolic acid B suppresses maturation of human monocyte-derived dendritic cells by activating PPAR��[J]. Br J Pharmacol, 2011,164(8):2042-2053.
[28]
ZHANG Q,ZHANG Y,LU L H, et al. Molecular regulation mechanism of PPARs in lipid disorder and inflammation in coronary heart disease and its application in traditional Chinese medicine[J]. China J Tradit Chin Med(�л���ҽҩ��־),2017,32(8):3623-3625.
[29]
WANG G,JIANG M,ZHU M D, et al. Study on the syndrome of stagnant blockade of heart blood and yin deficiency of heart and kidney of coronary heart disease through proteomics[J]. Liaoning J Tradit Chin Med(������ҽ��־),2011,38(3):405-407.
[30]
XU S X,ZHANG J P,ZHONG A Q, et al. Time sequence features of salvianolic acid B-regulated exression of hypoxia inducible factor l�� in rats following cerebral ischemia reperfusion[J]. Chin J Geriatr Heart Brain Vessel Dis(�л���������Ѫ�ܲ���־),2012,14(4):425-427.