基于网络药理学和分子对接探讨清热利胆颗粒治疗胆石症的作用机制  

Integrated Molecular Docking with Network Pharmacology to Study the Molecular Mechanism of Qingrelidan Granules in Treating Calculous Cholecystitis

作　　者：李积强 齐清会[2] 刘德 张桂信[1,2] LI Jiqiang;QI Qinghui;LIU De;ZHANG Guixin(Dalian Medical University,Dalian 116000,Liaoning,China;The First Affiliated Hospital of Dalian Medical University,Dalian 116011,Liaoning,China)

机构地区：[1]大连医科大学,辽宁大连116000 [2]大连医科大学附属第一医院,辽宁大连116011

出　　处：《实用中医内科杂志》2023年第10期35-39,I0007-I0010,共9页Journal of Practical Traditional Chinese Internal Medicine

基　　金：国家自然科学基金项目(82174136);辽宁省卫健委中医药临床重点专科能力建设项目(辽卫办2019[169]号)。

摘　　要：目的 基于网络药理学及分子对接探讨清热利胆颗粒治疗胆石症的作用机制。方法 通过检索TCMSP数据库获取清热利胆颗粒相关药物的主要活性成分和潜在作用靶点。利用Genecards数据库获得胆石症相关靶点,并筛选出清热利胆颗粒治疗胆石症的潜在靶点。将潜在靶点导入String数据库构建潜在靶点的PPI网络,然后利用Cytoscape 3.9.0软件绘制“药物-成分-靶点”网络图。再对核心靶标进行GO富集分析和KEGG通路富集分析。最后使用AutoDOCK1.5.6软件对活性成分和相关靶点进行分子对接。结果 经TCMSP数据库筛选后得到清热利胆颗粒活性成份共75种,主要参与成分为槲皮素、山柰酚、β-谷固醇、豆甾醇、柚皮素等,涉及胆石症相关靶点107个,通过PPI网络分析后我们得知AKT1、IL-6、TNF、EGFR、JUN是核心靶点。GO富集分析的结果显示清热利胆颗粒涉及生物过程为1407个,涉及细胞组成67个,而涉及分子功能119个。主要通过脂质结合、氧化还原酶活性、转录因子结合、信号受体调节活性、DNA结合转录因子结合等分子功能发挥作用。KEGG富集分析显示清热利胆颗粒涉及通路160条,主要通调控化学致癌-受体激活、PI3K-Akt信号通路、脂质和动脉粥样硬化、癌症中的蛋白多糖、HIF-1通路等相关通路发挥作用。结论 清热利胆颗粒主要作用于AKT1、IL6、TNF、EGFR等靶点并通过PI3K-Akt、癌症中的蛋白多糖相互作用及HIF-1等信号通路来促进炎症及癌症细胞凋亡和抑制其增殖从而发挥对胆石症的抗炎、抗肿瘤的治疗作用。此外发现EGFR蛋白是预防结石复发的关键靶点。Objective To explore the mechanism of Qingrelidan granule in the treatment of calculous cholecystitis based on net-work pharmacology and molecular docking.Methods The main active components and potential targets of drugs related to Qingrel-idan granules were obtained by searching TCMSP database.Genecards database was used to obtain the related targets of calculous cholecystitis,and the potential targets of Qingrelidan granules for the treatment of calculous cholecystitis were screened.Potential targets were imported into String database to construct PPI network of potential targets,and then the"drug-component-target"network diagram was drawn by Using Cytoscape 3.9.0 software.GO enrichment analysis and KEGG pathway enrichment analysis were performed for the core targets.Finally,AutoDOCK1.5.6 software was used for molecular docking of active ingredients and related targets.Results After screening by TCMSP database,75 kinds of active ingredients of Qingrelidan granules were ob-tained,including quercetin,kaempferol,β-sitosterol,stigmasterol,naringin,etc.,and 107 targets related to calculi cholecys-titis were involved.Through PPI network analysis,AKT1,IL6,TNF,EGFR and JUN were the core targets.The results of GO enrichment analysis showed that There were 1407 biological processes,67 cell compositions and 119 molecular functions involved in Qingrelidan granules.Mainly through lipid binding,oxidoreductase activity,transcription factor binding,signaling receptor reg-ulator activity,DNA-binding transcription factor binding and other molecular functions.KECG enrichment analysis showed that Qingreligan granules were involved in 160 pathways,mainly through Chemical carcinogenesis-receptor activation,PI3K-Akt signaling pathway,Lipid and atherosclerosis、HIF-1 signaling pathway HIF-1 pathway and other related pathways.Conclu-sion Qingreligan granule mainly acts on AKT1,IL-6,TNF,EGFR and other targets,and promotes inflammation and cancer cell apoptosis and inhibits proliferation through PI3K-Akt,Proteoglycans in cancer and HIF

关 键 词：胆石症 清热利胆颗粒 网络药理学 分子机制 

分 类 号：R289[医药卫生—方剂学]