摘要
目的基于网络药理学结合分子对接技术探究石榴皮治疗腹泻的作用机制。方法通过TCMSP数据库获取石榴皮的活性成分和潜在作用靶点;GeneCards、OMIM、DisGeNET数据库进行检索获得腹泻的潜在作用靶点,筛选两者交集靶点;应用Cytoscape软件构建蛋白相互作用(PPI)图并筛选核心靶点。通过DAVID数据库进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析,最后采用AutoDock软件进行分子对接验证。结果获得7个石榴皮主要化学成分,石榴皮与腹泻共同靶点114个。PPI分析显示,肿瘤抗原p53(TP53)、蛋白激酶B1(Akt1)、肿瘤坏死因子(TNF)、白细胞介素-6(IL-6)、胱天蛋白酶33(CASP)等可能为治疗关键靶点。通过KEGG分析表明,石榴皮可能通过癌症通路、磷脂酰肌醇3-激酶(PI3K)/Akt信号通路等起到治疗腹泻的作用。分子对接表明关键活性成分与核心靶点均可自发结合。结论通过网络药理学和分子对接技术揭示石榴皮可以通过多成分、多靶点、多途径治疗腹泻,为后续研究提供理论依据。
Objective To explore the mechanism of pomegranate peel in treatment of diarrhea based on network pharmacology and molecular docking technology.Methods The active chemical components of pomegranate peel and the corresponding targets were obtained from TCMSP databases,and the disease targets of diarrhea were retrieved using GeneCards,OMIM,and DisGeNET database,following by filtering the intersection of the two.Cytoscape 3.9.1 software was used to construct the PPI network of the intersection targets and screen the core targets.DAVID database was used for gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of potential targets of pomegranate peel in treatment of diarrhea,and AutoDock software was used for further verified by molecular docking.Results 7 Main chemical constituents of pomegranate peel were screened out,and 114 intersection targets between pomegranate peel and diarrhea were obtained.Topology analysis of PPI network showed that pomegranate peel alleviated diarrhea mainly acting the core targets TP53,Akt1,TNF,IL-6,CASP3,etc.The KEGG enrichment analysis showed that pomegranate peel might play a therapeutic role through the cancer pathway,PI3K/Akt signaling pathway,and so on.Molecular docking showed that the key active ingredients and the core targets could all bind spontaneously.Conclusion Network pharmacology combined with molecular docking proved that pomegranate peel could treat diarrhea through multi-component,multi-target and multi-pathway,which provides theoretical basis for its further in-depth research.
作者
卢永慧
张立华
王京龙
张肖
刘婧
刘雪
高丽丽
LU Yong-hui;ZHANG Li-hua;WANG Jing-long;ZHANG Xiao;LIU Jing;LIU Xue;GAO Li-li(College of Pharmaceutical Sciences,Shandong University of Traditional Chinese Medicine,Jinan 250355,China;College of Food Science and Pharmaceutical Engineering,Zaozhuang University,Zaozhuang 277160,China;College of Life Sciences,Shihezi University,Shihezi 832061,China)
出处
《现代药物与临床》
CAS
2023年第10期2436-2443,共8页
Drugs & Clinic
基金
山东省重点研发计划项目(2022TZXD0019)。
