痛泻要方主要有效成分的多靶点网络构建与机制分析
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摘要
目的:对痛泻要方主要有效成分构建多靶点网络和机制分析,以阐明痛泻要方多成分、多靶点、多通路治疗肠易激综合征的药理机制。方法:利用数据库筛选出肠易激综合征相关基因,结合文献与数据库获取痛泻要方的目标成分和靶点,通过注释、可视化和集成发现数据库(DAVID)和京都基因组百科全书(KEGG)对靶点基因进行功能注释和通路富集分析,利用网络数据集成、分析和可视化(Cytoscape)软件构建痛泻要方的成分、靶点、疾病通路的相关网络并进行分析。结果:筛选得到痛泻要方中25种主要有效成分,相关靶点37个。以此为基础构建了目标成分-有效靶点(C-T)网络和成分-靶点-通路(C-T-P)网络,获得重要成分12个,核心靶点11个,关键通路26条,功能涉及胃肠道血管平滑肌、内分泌调节和神经免疫。结论:痛泻要方不同有效成分作用于多靶点网络,通过炎症反应调节、肠道感觉功能调节、免疫反应调节、精神心理调节和肠道感染与菌群紊乱调节等多途径发挥协同作用。
Objective: A multi-target network and mechanism analysis of the main effective components of Tongxie Yaofang was carried out to illustrate the multi-component, multi-target and multi-pathway pharmacological mechanism of Tongxie Yaofang in treating irritable bowel syndrome. Method: Genes associated with irritable bowel syndrome were screened out through databases. Literatures and databases were retrieved to obtain the components and targets of Tongxie Yaofang. Functional annotation and pathway enrichment analysis of target genes were carried out by the Database for Annotation,Visualization and Integrated Discovery(DAVID) and Kyoto Encyclopedia of Genes and Genomes(KEGG) databases. The components,targets and disease pathwaysrelated networks of Tongxie Yaofang were constructed and analyzed by Cytoscape software. Result: A total of 25 main active components of Tongxie Yaofang were screened out,involving 37 related targets. Based on this,the target component-effective target(C-T) network and the component-target-pathway(C-T-P) network were constructed,including 12 important components and 11 core targets and 26 crucial pathways. The functions of target genes involved gastrointestinal vascular smooth muscle, endocrine regulation and nerve immunity.Conclusion: Various effective components of Tongxie Yaofang act on multiple targets network,and then have a synergistic effect by multiple channels,including regulating inflammation,intestinal sensory function regulation,immune response,psychological adjustment and intestinal infection and flora disorder.
Objective: A multi-target network and mechanism analysis of the main effective components of Tongxie Yaofang was carried out to illustrate the multi-component, multi-target and multi-pathway pharmacological mechanism of Tongxie Yaofang in treating irritable bowel syndrome. Method: Genes associated with irritable bowel syndrome were screened out through databases. Literatures and databases were retrieved to obtain the components and targets of Tongxie Yaofang. Functional annotation and pathway enrichment analysis of target genes were carried out by the Database for Annotation,Visualization and Integrated Discovery(DAVID) and Kyoto Encyclopedia of Genes and Genomes(KEGG) databases. The components,targets and disease pathwaysrelated networks of Tongxie Yaofang were constructed and analyzed by Cytoscape software. Result: A total of 25 main active components of Tongxie Yaofang were screened out,involving 37 related targets. Based on this,the target component-effective target(C-T) network and the component-target-pathway(C-T-P) network were constructed,including 12 important components and 11 core targets and 26 crucial pathways. The functions of target genes involved gastrointestinal vascular smooth muscle, endocrine regulation and nerve immunity.Conclusion: Various effective components of Tongxie Yaofang act on multiple targets network,and then have a synergistic effect by multiple channels,including regulating inflammation,intestinal sensory function regulation,immune response,psychological adjustment and intestinal infection and flora disorder.
引文
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[12]LI T X,HU L,YANG X H.A sensitive UPLC-MS/MS method for simultaneous determination of eleven bioactive components of Tong-Xie-Yao-Fang decoction in ratbiological matrices[J].J Chromatogr B,2014,944:90-100.
[13]Hopkins A L.Network pharmacology[J].Nat Biotechnol,2007,25(10):1110-1111.
[14]范骁辉,程翼宇,张伯礼.网络方剂学:方剂现代研究的新策略[J].中国中药杂志,2015,40(1):1-6.
[15]高宁,李天聪,程玉鹏,等.龙胆裂环环烯醚萜类有效成分作用机理的网络药理学研究[J].化学工程师,2017,31(1):14-16.
[16]刘鑫馗,吴嘉瑞,张晓朦,等.基于网络药理学的参附汤作用机制分析[J].中国实验方剂学杂志,2017,23(16):211-218.
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[18]蔡菲菲,李晓燕,董姝,等.基于网络药理学的茵陈蒿汤“异病同治”研究[J].世界科学技术—中医药现代化,2016,18(9):1507-1514.
[19]ZHAO F,LI G C,YANG Y H,et al.A network pharmacology approach to determine active ingredients and rationality of herb combinations of ModifiedSimiaowan for treatment of gout[J].J Ethnopharmacol,2015,168:1-16.
[20]陈天阳,薛建华,侯天禄,等.苍术酮对急性肺损伤小鼠血清细胞因子和TLR7信号通路的影响[J].中国中医急症,2017,26(6):952-955.
[21]姚凤,周清燕,熊瑛,等.β-谷甾醇对脂多糖诱导的小鼠急性肺损伤的保护作用研究[J].中国农学通报,2015,31(2):55-61.
[22]石超峰,殷中琼,魏琴,等.α-松油醇对大肠埃希菌的抑菌作用及其机理研究[J].畜牧兽医学报,2013,44(5):796-801.
[23]廖芳,杨振德,黄庆华,等.麝香草酚和香荆芥酚对痢疾杆菌和肠炎常见菌的体外抗菌效应[J].医药导报,2005,24(10):868-870.
[24]王岚,梁日欣,曹莹,等.升麻苷和5-O-甲基维斯阿米醇苷对TNF-α所致大鼠胸主动脉平滑肌细胞增殖的影响[J].中国中药杂志,2008,33(17):2157-2160.
[25]郑世存,李晓宇,欧阳兵,等.芍药苷药理作用研究新进展[J].中国药物警戒,2012,9(2):100-103.
[26]旺建伟,叶虹玉,殷越,等.痛泻要方对肠易激综合征内脏高敏性大鼠结肠组织肥大细胞活化、P物质表达及相关性的影响[J].中华中医药杂志,2014,29(6):1982-1986.
[27]李翠芹,贺浪冲.白细胞膜色谱模型建立与白术中TLT4受体拮抗活性成分筛选研究[J].中国科学,2005,35(6):545-550.
[28]胡云飞,徐国兵.牡丹皮及其主要成分丹皮酚的药理作用研究进展[J].安徽医药,2014,18(4):589-592.
[29]陈一竹,杨文龙,郭玲玉,等.白术内酯3抗血小板作用及其机制[J].国际药学研究杂志,2016,43(3):514-517.
[2]李晓青,常敏,许东,等.中国肠易激综合征流行病学调查现状分析[J].胃肠病学和肝病学杂志,2013,22(8):734-739.
[3]刘雁冰,袁耀宗.肠道炎症引起功能性胃肠动力异常的机制[J].诊断学理论与实践,2006,5(1):16-19.
[4]Bensoussan A,Talley N J,Hing M,et al.Treatment of irritable bowel syndrome with Chinese herbal medicine[J].JAMA,1998,280(18):1585-1589.
[5]Thompson D L.Complementary healthcare practices:east meets west:The use of traditional Chinese medicine for gastrointestinal disorders[J].Gastroenterol Nurs,2003,26(6):266-268.
[6]梁瑞峰,葛文静,王慧森,等.痛泻要方加减引经药防风对肠易激综合征大鼠内脏敏感性及脑肠轴不同靶点脑肠肽的影响[J].中国实验方剂学杂志,2018,24(2):152-157.
[7]赵玉斌,李佃贵.痛泻要方对肠道高敏感性肠易激综合征大鼠模型疗效和作用机理的研究[J].中成药,2006,28(6):852-855.
[8]余萍,张成,陈敏,等.痛泻要方缓解肠易激综合征患者内脏高敏机制研究进展[J].辽宁中医杂志,2016,43(1):216-217.
[9]肖亚,熊艾君,何文智,等.痛泻要方对腹泻型肠易激综合征大鼠胃肠激素的影响[J].中国当代医药,2010,17(3):20-22.
[10]李冬华,李春淼,李伍善,等.痛泻要方对肠易激综合征模型大鼠血管活性肠肽的影响[J].时珍国医国药,2007,18(9):2098-2099.
[11]YAN Z X,YANG X H.Qualitative and quantitative analysis of chemical constituents in traditional Chinese medicinal formula Tong-Xie-Yao-Fang by highperformance liquid chromatography/diode array detection/electrospray ionization tandem mass spectrometry[J].Anal Chim Acta,2011,691(1/2):110-118.
[12]LI T X,HU L,YANG X H.A sensitive UPLC-MS/MS method for simultaneous determination of eleven bioactive components of Tong-Xie-Yao-Fang decoction in ratbiological matrices[J].J Chromatogr B,2014,944:90-100.
[13]Hopkins A L.Network pharmacology[J].Nat Biotechnol,2007,25(10):1110-1111.
[14]范骁辉,程翼宇,张伯礼.网络方剂学:方剂现代研究的新策略[J].中国中药杂志,2015,40(1):1-6.
[15]高宁,李天聪,程玉鹏,等.龙胆裂环环烯醚萜类有效成分作用机理的网络药理学研究[J].化学工程师,2017,31(1):14-16.
[16]刘鑫馗,吴嘉瑞,张晓朦,等.基于网络药理学的参附汤作用机制分析[J].中国实验方剂学杂志,2017,23(16):211-218.
[17]刘洪,范欣生.三拗汤主要功效成分多靶点网络构建[J].中草药,2015,46(22):3370-3376.
[18]蔡菲菲,李晓燕,董姝,等.基于网络药理学的茵陈蒿汤“异病同治”研究[J].世界科学技术—中医药现代化,2016,18(9):1507-1514.
[19]ZHAO F,LI G C,YANG Y H,et al.A network pharmacology approach to determine active ingredients and rationality of herb combinations of ModifiedSimiaowan for treatment of gout[J].J Ethnopharmacol,2015,168:1-16.
[20]陈天阳,薛建华,侯天禄,等.苍术酮对急性肺损伤小鼠血清细胞因子和TLR7信号通路的影响[J].中国中医急症,2017,26(6):952-955.
[21]姚凤,周清燕,熊瑛,等.β-谷甾醇对脂多糖诱导的小鼠急性肺损伤的保护作用研究[J].中国农学通报,2015,31(2):55-61.
[22]石超峰,殷中琼,魏琴,等.α-松油醇对大肠埃希菌的抑菌作用及其机理研究[J].畜牧兽医学报,2013,44(5):796-801.
[23]廖芳,杨振德,黄庆华,等.麝香草酚和香荆芥酚对痢疾杆菌和肠炎常见菌的体外抗菌效应[J].医药导报,2005,24(10):868-870.
[24]王岚,梁日欣,曹莹,等.升麻苷和5-O-甲基维斯阿米醇苷对TNF-α所致大鼠胸主动脉平滑肌细胞增殖的影响[J].中国中药杂志,2008,33(17):2157-2160.
[25]郑世存,李晓宇,欧阳兵,等.芍药苷药理作用研究新进展[J].中国药物警戒,2012,9(2):100-103.
[26]旺建伟,叶虹玉,殷越,等.痛泻要方对肠易激综合征内脏高敏性大鼠结肠组织肥大细胞活化、P物质表达及相关性的影响[J].中华中医药杂志,2014,29(6):1982-1986.
[27]李翠芹,贺浪冲.白细胞膜色谱模型建立与白术中TLT4受体拮抗活性成分筛选研究[J].中国科学,2005,35(6):545-550.
[28]胡云飞,徐国兵.牡丹皮及其主要成分丹皮酚的药理作用研究进展[J].安徽医药,2014,18(4):589-592.
[29]陈一竹,杨文龙,郭玲玉,等.白术内酯3抗血小板作用及其机制[J].国际药学研究杂志,2016,43(3):514-517.