基于网络药理学和分子对接技术探讨经方黄芩汤治疗溃疡性结肠炎机制研究  

Potential Mechanism of Huangqin Decoction(黄芩汤)for the Treatment of Ulcerative Colitis Based on Network Pharmacology and Molecular Docking Techniques

作　　者：顾立梅[1,2] 刘培钊 孔维乾 潘程宇 李慧 田耀洲[1,2] GU Limei;LIU Peizhao;KONG Weiqian;PAN Chengyu;LI Hui;TIAN Yaozhou(Affiliated Hospital of Integrated Traditional Chinese and Western Medicine,Nanjing University of Chinese Medicine,Nanjing 210028,Jiangsu,China;Jiangsu Province Academy of Traditional Chinese Medicine,Nanjing 210028,Jiangsu,China;Affiliated Jinling Hospital,Medical School of Nanjing University,Nanjing 210002,Jiangsu,China;Liyang Hospital of Chinese Medicine,Liyang 213300,Jiangsu,China)

机构地区：[1]南京中医药大学附属中西医结合医院,江苏南京210028 [2]江苏省中医药研究院,江苏南京210028 [3]南京大学医学院附属金陵医院,江苏南京210002 [4]溧阳市中医医院,江苏溧阳213300

出　　处：《辽宁中医药大学学报》2022年第10期84-89,共6页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：国家中医药管理局中医循证实践能力建设研究(2019XZZX-XH007);江苏省中医药管理局科研项目(JD2019SZXYB05);田耀洲江苏省名老中医药专家传承工作室建设项目(20SGZS003);南京中医药大学自然科学基金项目(XZR2020030)。

摘　　要：目的基于网络药理学方法,探讨中医经典名方黄芩汤治疗溃疡性结肠炎的潜在分子作用机制,为其临床运用及研发提供一定的参考。方法基于TCMSP数据库检索获取黄芩汤的有效活性成分及其潜在的作用靶点,通过GeneCard、OMIM数据库检索溃疡性结肠炎(ulcerative colitis,UC)疾病相关靶点,将两者取交集获得黄芩汤治疗UC的潜在靶点93个,继而将获得的有效活性成分及潜在作用靶点导入Cytoscape软件,绘制“黄芩汤-活性化合物-UC作用靶点”的网络图,筛选关键活性成分;并将潜在靶点导入STRING数据库,构建PPI网络,筛选黄芩汤治疗UC的核心靶点;同时利用Metascape平台对核心靶点进行GO生物学过程富集分析和KEGG通路注释分析。结果黄芩汤治疗UC的主要活性成分为槲皮素(quercetin)、山柰酚(kaempferol)、汉黄芩素(wogonin)、黄芩素(baicalein)、β-胡萝卜素(β-carotene)等;可作用于AKT1、JUN、IL-6、VEGFA、STAT3、CASP3、EGFR等关键靶点,激活或抑制PI3K/Akt、MAPK、endocrine resistance、Th17 cell differentiation、NF-κB、AGE-RAGE、JAK-STATs等相关通路,涉及内毒素反应、调节小分子代谢、调节活性氧代谢、调控凋亡信号通路、负调控细胞增殖等生物过程。同时,通过Swissdock平台分子对接验证表明:黄芩汤的关键活性成分kaempferol、quercetin、wogonin与核心作用靶点AKT1结合能均小于-5.0 kJ/mol。结论研究初步揭示了黄芩汤治疗UC的多成分、多靶点、多通路的作用机制,为经方黄芩汤的临床开发以及应用提供科学依据。Objective To explore the material basis and the potential mechanism of action of Huangqin Decoction(黄芩汤)for the treatment of ulcerative colitis(UC)based on the network pharmacological approach and molecular docking technology,providing some reference for the clinical application and development of the classical formula.Methods The potential active ingredients in Huangqin Decoction and their targets were obtained from TCMSP database,and the targets related to UC disease were retrieved from GeneCard and OMIM databases,and 93 potential targets of Huangqin Decoction for UC were obtained by intersecting the two.Cytoscape software was adopted to create the network diagram of“Huangqin Decoction active ingredient-potential target”to screen the key ingredients by importing potential targets and active ingredients.Meanwhile,the potential targets were imported into STRING database to construct a PPI network,and the core targets of Huangqin Decoction for UC treatment were screened.The Metascape platform was used to perform GO(gene ontology)biological process enrichment analysis and KEGG(KEGG pathway analysis)pathway annotation analysis on the drug-disease intersection targets,and finally the molecular docking verification was performed by Swiss Dock Web Site.Results The main active ingredients of Huangqin Decoction for UC treatment are quercetin,kaempferol,wogonin,baicalein,β-carotene,etc.The core targets are AKT1,JUN,IL6,VEGFA,STAT3,MYC,CASP3,EGFR,etc.Huangqin Decoction treatment of UC mainly acts on signaling pathways such as cancer pathway,MAPK signaling pathway,TNF signaling pathway,insulin resistance,JAK-STAT pathway,Th17 cell differentiation,NF-κB,and other related pathways,which are involved in endotoxin response,regulation of apoptotic signaling pathway,regulation of small molecule metabolic processes,reactive oxygen species metabolic processes,negative regulation of cell proliferation and other biological processes.Meanwhile,the molecular docking verification by Swissdock platform showed that the binding

关 键 词：网络药理学 分子对接 黄芩汤 溃疡性结肠炎 潜在作用机制 

分 类 号：R574.62[医药卫生—消化系统]