Abstract��OBJECTIVE To analyze active ingredients,targets,pathways and biological processes of xianglian pills by means of network pharmacology and explore its pharmacodynamics material base and mechanism of action.METHODS Active ingredients and corresponding targets of xianglian pills were obtained by using TCMSP database and BATMAN-TCM analytical platform,the network of xianglian pills active ingredients-targets was constructed by using Cytoscape 3.5.1 software, using the STRING platform to build protein-protein interaction; GO bioprocess enrichment and clustering analysis of target genes were finished by using BINGO and MCODE plug-ins; KEGG signaling pathways of target genes were analyzed by means of DAVID database.RESULTS Eleven active ingredients in xianglian pills act on 291 potential targets. these targets participate in eighteen major GO biological process adjustment sub-clusters of the inflammatory response, leukotriene metabolism, lipid metabolism, apoptosis, smooth muscle contraction and platelet activation etc. involve in thirty-three signal pathways of seven categories: inflammation, metabolism,signal transduction, cancer, secretion of digestive juices, ardiovascular system etc.CONCLUSION The different therapeutic value, pharmacodynamic substances and molecular mechanism of Xianglian pills in the treatment of inflammation,diabetes,cancer and cardiovascular diseases have been preliminarily elucidated, which provides new clues for the development of its clinical application.
������, ��Ծ��. ���������û��Ƶ�����ҩ��ѧ�о�[J]. �й�ҩѧ��־, 2018, 53(24): 2079-2089.
WANG Bo-long, LI Yue-wen. Research on Network Pharmacology of Action Mechanism of Xianglian Pills. Chinese Pharmaceutical Journal, 2018, 53(24): 2079-2089.
HUANG Y P,LIU D L,LIU X Y, et al. HPLC fingerprint of xianglian pills. China Tradit Herb Drugs(�в�ҩ),2011,42(10):2014-2016.
[2]
KONG J J,ZHU J J,WANG Z M, et al. Quantitative analysis of four alkaloids in xianglian preparations by QAMS method. China J Chin Mater Med(�й���ҩ��־),2011,36(11):1445-1448.
[3]
CHEN Y J,WU Y G,FANG H H, et al. Simultaneous determination of contents of five components in xianglian pills by HPLC. Chin J Hosp Pharm(�й�ҽԺҩѧ��־),2016,36(12):972-975.
[4]
TAN X M, LONG Q.Study on pharmacodynamics of analgesic,antidiarrhea,anti-inflammatory and small intestine propelling in effective parts of xianglian pills. J Southern Med Univ(�Ϸ�ҽ�ƴ�ѧѧ��),2008,28(3):499-500.
[5]
ZHANG X F,QIAO C X,CHEN X F, et al. Observation on the effect of xianglian pill on chemotherapy related diarrhoea naked rat model. Chin Tradit Pat Med(�г�ҩ),2016,38(7):1598-1601.
[6]
MA H,HU Y R,ZOU Z Y, et al. Preliminary evaluation of antihyperglycemic effect of Rhizoma Coptidis alkaloids and their structure-activity relationships. Chin Pharmacol Bull(�й�ҩ��ѧͨ��),2015,31(11):1575-1579.
[7]
SUN H,LU F E,WANG Z S, et al. Molecular mechanism of berberine to improve insulin NIT-1 cell apoptosis induced by high sugar and high lipids. Chin Pharmacol Bull(�й�ҩ��ѧͨ��),2008, 24 (6):762-765.
[8]
MA H G,YAO L F.Berberine in the treatment of central nervous system related diseases. J Chin Pract Diag Ther(�л�ʵ�������������־),2017,31(9):929-931.
[9]
QIN H L,FANG L H,GONG L L, et al. Application of berberine in the prevention and treatment of myocardial ischemic diseases:CN102000073A. China,2011-04-06.
[10]
YUAN W F,TU M Y,CHEN C, et al. Network pharmacology study of compound danshen dropping pill based on molecular docking and recognition of biological network function modules. Chin Pharm J(�й�ҩѧ��־),2017,52(9):743-749.
[11]
ZHAO Q Q,LI X,ZENG M L, et al. A network pharmacology based study of regulation effects of the main active components in honghua injection on cerebrovascular disease network. Chin Pharm J(�й�ҩѧ��־),2015,50(16):1402-1407.
[12]
SHI R F,ZHANG R L. Research progress on the intracellular mechanisms of kallikrein-kinin system. J Med Postgrad(ҽѧ�о���ѧ��),2015,28 (5):534-538.
[13]
WEINREUTER M,KREUSSER M M,BECKENDORF J, et al. CaM kinase�� mediates maladaptive post-infarct remodeling and pro-inflammatory chemoattractant signaling but not acute myocardial ischemia/reperfusion injury. EMBO Mol Med,2014,6(10):1231-1245.
[14]
DONG Y,LU J G.The effects of aucklandia and coptis pills on cellular apoptosis and the expression of Bcl-2 and Bax mRNA in model rats with ulcerative colitis. West Chin Med J(����ҽѧ),2016,31(6):1046-1051.
[15]
SUN L M,LIU L F,ZHU H X, et al. Network pharmacology-based study on intervention mechanism of Huanglian Jiedu decoction in the treatment of Alzheimer��s disease. Acta Pharm Sin(ҩѧѧ��),2017,52(8):1268-1275.
[16]
CHAI H,YU J W,MA J L, et al. Effect of ilerberine in tumor necrosis factor-a induced inflammation. J Zhejiang Chin Med Univ(�㽭��ҽҩ��ѧѧ��),2011,35(4):489-491.
[17]
PAN X L, XIANG H, XIE Y F, et al. The anti-inflammatory mechanism of coptisine basing on the signal path of NF-��B in vitro. Chin J Antibiot(�й���������־),2013,38(12):951-954,959.
[18]
WANG Y,DING S L,QI X J, et al. Research progress on the pathogenesis and treatment of stress gastric ulcer. Tianjin J Tradit Chin Med(�����ҽҩ),2013,30(3):186-189.
[19]
WANG X N.Clinical observation of traditional Chinese medicine Coptis Chinensis treatment of type 2 diabetes mellitus. J Liaoning Univ Tradit Chin Med(������ҽҩ��ѧѧ��),2015,17(7):168-170.
[20]
CUI X L,WANG D Z,ZOU Z Y, et al. Study on hypoglycemic effect of epiberberine . Asia-Pacific Tradit Med(��̫��ͳҽҩ),2015,11(13):12-13.
[21]
ZHANG Q,XIAO X,FENG K, et al. Berberine moderates glucose and lipid metabolism through multipathway mechanism. Evid Based Complement Alternat Med,2011,2011:924851.
[22]
KO B S,CHOI S B,PARK S K, et al. Insulin sensitizing and insulinotropic action of berberine from Cortidis Rhizoma. Biol Pharm Bull,2005,28(8):1431-1437.
[23]
QIAN Y. A molecular epidemiology study on the type 2 diabetes susceptibilty in Chinese population . Nanjing:Nanjing Medical University,2012.
[24]
TU Y Q. Association analysis of polymorophisms in ADIPOQ gene with T2D in Chinese Han population. Wuhan:Huazhong University of Science and Technology,2015.
[25]
YANG Y,LUO B R,ZHAO D M, et al. Research progress on relationship of CD36 gene with type 2 diabetes mellitus glucolipid metabolism. Pract J Clin Med(ʵ��ҽԺ�ٴ���־),2017,14(6):279-282.
[26]
TANG J T. Association of The rs2268388 Polymorphism of ACACB gene With Diabetic mellitus and Diabetic kidney disease. Kunming:Kunming Medical University,2015.
[27]
YIN Z J, CAO Z W,YAN X M, et al. Study of synergistic mechanism in the combination of berberine and evodiamine from the perspective of miRNA. Chin Pharmacol Bull(�й�ҩ��ѧͨ��),2017,33(6):772-780.
[28]
MA W, ZHU M, ZHANG D, et al. Beriberi inhibits the proliferation and migration of breast cancer ZR-75-30 cells by targeting Ephrin-B2. Phytomedicine,2017,25:45-51.
[29]
LU J J,FU L,TANG Z, et al. Melatonin inhibits AP-2beta/h TERT, NF-kappa B/COX-2 and Akt/ERK and activates caspase/Cyto C signaling to enhance the antitumor activity of berberine in lung cancer cells. Oncotarget, 2016,7(3):2985-3001.
[30]
WANG J X. Berberine enhances Efficacy of EGFR inhibitors in gastric cancer through inhibition of EGFR/STAT3 signaling pathway. Beijing:Capital Medical University,2017.
[31]
SHI H L, LIU F,GUO X J, et al. Effects of berberine on proliferation, migration and adhesion of lung adenocarcinoma cell line A549. China Oncol(�й���֢��־),2009,19(12):910-914.
[32]
LI O. Inhibition effects and mechanisms of berberine on HepG2 Hepatoma cell proliferation and repopulation. Changchun:Jilin University,2013.
[33]
ZHU L H,BI W,LIU X D, et al. Induction of apoptosis by evodiamine involves both activation of mitotic arrest and mitotic slippage. Oncol Rep,2011,26(6):1447-1455.
[34]
YANG Y B J,WANG S, LI S, et al. Effects of compound daqiqi decoction combined cisplatin on Bcl-2/Bax expression of nude mice ovarian cancer subcutaneous transplanted tumor. China J Chin Mater Med(�й���ҩ��־),2015,40(8):1575-1579.
[35]
REN L P,LI X J,JING S J. Influence of sophoridine on proliferation and caspase-3/bcl-2/bax signaling pathway of human pancreatic cancer cell line capan-1 cells. Chin J Mod Appl Pharm(�й��ִ�Ӧ��ҩѧ),2017,34(3):325-328.
[36]
LI Z.The expression and clinical significance of Bid and Fas in cervucal cancer tissues. Chengdu:South-west Medical University,2017.
[37]
ZHANG M F.Antihypertensive effects of berberine. Eval Anal Drug-Use Hosp Chin(�й�ҽԺ��ҩ���������),2001,1(5):299-301.
[38]
WANG C M, LI J, LV X Y, et al. Ameliorative effect of berberine on endothelial dysfunction in diabetic rats induced by high-fat diet and streptozotocin. Eur J Pharmacol,2009,620(1/3):131-137.
[39]
WANG X Y,LIN J,PAN J Q. Pharmacological effects of berberine and its congeners on inhibition of myocardial hypertrophy and ventricular remodeling. Pharm Today(����ҩѧ),2012,22(1):46-50.
[40]
ZHAO H P,HONG Y,XIE J D, et al. Effect of berberine on left ventricular remodeling in renovascular hypertensive rats. Acta Pharm Sin(ҩѧѧ��),2007,42(3):336-341.
[41]
HOU P F,CHEN W X,ZHAO X H, et al. Analysis of chemical composition of the essential oil from Radix Aucklandiae by GC-MS and the effect on platelet aggregation. Chin J Exp Tradit Med Form(�й�ʵ�鷽��ѧ��־), 2008,14 (7):26-30.
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