基于网络药理学与分子对接方法探讨白术七物颗粒对慢传输型便秘的作用机制  

Mechanism of Baizhu Qiwu Granules on slow transit constipation based on network pharmacology and molecular docking

作　　者：罗宏标[1,2] 丁宁[2] 唐清珠 林仁敬[4] 张涛[2] 何永恒[3] Luo Hongbiao;Ding Ning;Tang Qingzhu;Lin Renjing;Zhang Tao;He Yongheng(Department of Anorectal Surgery,Chenzhou NO.1 People′s Hospital,Chenzhou Hunan 423000;Hunan University of Chinese Medicine,Changsha Hunan 410208;Hunan Institute of Traditional Chinese Medicine,Changsha Hunan 410013;Department of Anorectal Surgery,Hunan Academy of Traditional Chinese Medicine Affiliated Hospital,Changsha Hunan 410005)

机构地区：[1]郴州市第一人民医院,湖南郴州423000 [2]湖南中医药大学,湖南长沙410208 [3]湖南中医药研究院,湖南长沙410013 [4]湖南中医药大学第二附属医院,湖南长沙410005

出　　处：《山西中医药大学学报》2022年第4期356-363,共8页Journal of Shanxi University of Chinese Medicine

基　　金：湖南省自然科学基金面上项目(2021JJ30419,2021JJ30517);湖南省郴州市科学技术局科技发展计划项目(zdyf201962);湖南省中医药科研计划课题青年项目(202103);湘南学院科学技术项目(2019-28)。

摘　　要：目的:探讨白术七物颗粒治疗慢传输型便秘(STC)的作用机制。方法:通过中药系统药理学分析平台(TCMSP)及BATMAN-TCM数据库检索白术七物颗粒中药物的活性成分与预测靶点;通过GEO、GeneCards、PharmGkb、DrugBank、TTD数据库挖掘STC的相关靶点基因,取并集得到STC的疾病靶点;通过Cytoscape软件与STRING数据库构建“疾病-药物-成分-靶点网络图”及蛋白互作网络图。对共有基因进行GO和KEGG富集分析,最后通过SYBYL-X 2.0软件进行分子对接验证。结果:筛选出白术七物颗粒有效成分61个,共有基因81个,其中核心成分为槲皮素、β-谷甾醇和6,7-dimethoxy-2-(2-phenylethyl)chromone。核心靶点基因分别为AKT1、TP53、CASP3、IL1B、CCND1、EGFR、PTGS2。白术七物颗粒有效成分可能作用于膜筏、膜微域、小窝等,调节细胞对化学应激的反应、对异种刺激的反应、对营养水平的反应、对氧化应激的反应等生物学过程,并通过IL-17信号通路、肿瘤坏死因子信号通路、细胞凋亡等治疗STC。分子对接显示主要有效成分檞皮素能与目标靶蛋白受体较好地结合。结论:根据白术七物颗粒治疗慢传输型便秘多成分、多靶点作用的特点,初步预测了其可能的分子作用机制,为后续研究提供了基础。Objective:To investigate the mechanism of Baizhu Qiwu Granules in the treatment of slow transit constipation.Methods:The active components and predicted targets in Baizhu Qiwu Granules were retrieved through the Traditional Chinese Medicine System Pharmacology Analysis Platform(TCMSP)and BATMAN-TCM database.The related target genes of slow transit constipation were mined through GEO,GeneCards,PharmGkb,DrugBank,and TTD databases,and the disease targets of STC were obtained by taking the union.The“disease-drug-component-target network map”and the protein interaction network map were constructed by Cytoscape software and STRING database.GO and KEGG enrichment analysis were performed on the common genes,and finally the molecular docking verification was performed by SYBYL-X 2.0 software.Results:There were 61 active ingredients in Baizhu Qiwu Granules,and 81 genes in total,of which the core ingredients were quercetin,beta-sitosterol and 6,7-dimethoxy-2-(2-phenylethyl)chromone.The core target genes were AKT1,TP53,CASP3,IL1B,CCND1,EGFR and PTGS2,respectively.The active ingredients of Baizhu Qiwu Granules may act on membrane raft,membrane microdomain and caveola,etc.And they may regulate the biological response of cells to chemical stress,xenobiotic stimulus,nutrient levels,and oxidative stress.Besides,these active ingredients could treat STC through IL-17 signaling pathway,TNF signaling pathway and apoptosis.Molecular docking showed that quercetin,the main active ingredient,could bind well to the target protein receptor.Conclusion:This study preliminarily predicted the possible molecular mechanism of action of Baizhu Qiwu Granules in the treatment of slow transit constipation,and provided a basis for subsequent research.

关 键 词：白术七物颗粒 网络药理学 分子对接 机制 慢性传输型便秘 

分 类 号：R574.62[医药卫生—消化系统]