摘要
目的利用网络药理学和分子对接技术探讨护胃散治疗化疗性恶心和呕吐(CINV)的关键靶点及通路,挖掘作用机制。方法通过TCMSP及BATMAN-TCM数据库筛选出护胃散活性成分,并通过SwissTargetPrediction预测靶点。运用OMIM、GeneCards、TTD数据库筛选CINV疾病基因,将筛选的药物靶点与疾病基因取交集,作为护胃散治疗CINV的潜在靶点。通过STRING数据库筛选结合Cytoscape3.7.2软件构建中药成分-CINV-靶点蛋白相互作用(PPI)网络图,采用Metascape数据库对交集靶点进行GO与KEGG富集分析,利用AutoDock Vina分子对接验证药物与靶点的结合力。结果共筛选出护胃散潜在靶点384个,CINV相关靶点413个,交点靶点基因109个。经Network Analyzer工具网络拓扑参数分析共获得10个核心靶点信息。GO富集分析共得到1173条相关条目,结果显示,生物过程主要与蛋白质磷酸化的正向调节、腺体发育和凋亡信号通路的调控有关;细胞组分主要涉及对氮化物的反应、细胞及其成分迁移正向调节、增殖负调节、凋亡信号通路的正向调节;分子功能包括蛋白结合、相同蛋白结合、酶结合、神经递质受体活性。KEGG信号通路共得到198条,富集程度最高通路为癌症通路、乙型肝炎等。分子对接结果表明,STAT3、TP53、MAPK3、AKT1、MAPK1、HSP90AA1与活性成分β-谷甾醇、槲皮素、山柰酚、连翘苷、汉黄芩素及白桦脂酸结合能≤-5 kcal/mol,结合能力稳定。结论护胃散通过调节STAT3、TP53、MAPK3、AKT1、MAPK1、HSP90AA1等潜在靶点,参与癌症通路、细胞凋亡、细胞衰老等通路延缓细胞衰老凋亡及抗氧化来治疗CINV,多通路、多靶点地发挥药理作用。
Objective To explore the key targets and pathways of Huwei Powder in the treatment of chemotherapy-induced nausea and vomiting(CINV)using network pharmacology and molecular docking technology;To explore its mechanism.Methods The active components of Huwei Powder were screened out by TCMSP and BATMAN-TCM databases,and the target prediction was predicted by SwissTargetPrediction.The OMIM,GeneCards,and TTD databases were used to screen CINV disease genes,and the screened drug targets were intersected with disease genes as potential targets for Huwei Powder in the treatment of CINV.Through STRING database screening combined with Cytoscape 3.7.2 software,the PPI network diagram of“TCM components-CINV targets”was constructed,and the Metascape database was used to perform GO and KEGG enrichment analysis of intersection targets.AutoDock Vina molecular docking was used to verify the binding force of drugs and targets.Results A total of 384 potential targets for Huwei Powder,413 related targets for CINV,and 109 targets for intersection genes were screened.A total of 10 pieces of core target information were obtained by analyzing the network topology parameters of the Network Analyzer tool.GO enrichment analysis obtained a total of 1173 related items,and the results showed that biological processes were mainly related to positive regulation of protein phosphorylation,gland development and apoptotic signaling pathways.Cellular component mainly involved response to nitrogen compounds,positive regulation of migration of cells and their components,negative regulation of proliferation,and positive regulation of apoptotic signaling pathways.Molecular functions included protein binding,identical protein binding,enzyme binding,and neurotransmitter receptor activity.A total of 198 KEGG signaling pathways were obtained,and the most enriched pathways were cancer pathway and hepatitis B.The molecular docking results showed that STAT3,TP53,MAPK3,AKT1,MAPK1 and HSP90AA1 had a binding energy of≤-5 kcal/mol with the active components
作者
弓鹏
芦亦旻
邓晓鹏
李曼
李孝波
GONG Peng;LU Yimin;DENG Xiaopeng;LI Man;LI Xiaobo(Shanxi University of Chinese Medicine,Jinzhong 030619,China;Yingze District Hospital of Traditional Chinese Medicine,Taiyuan 030000,China;Shanxi Combined Hospital of Traditional Chinese and Western Medicine,Taiyuan 030000,China)
出处
《中国中医药图书情报杂志》
2024年第3期56-63,共8页
Chinese Journal of Library and Information Science for Traditional Chinese Medicine
基金
山西特色优势名方验方和诊疗技术研发引导专项-门氏功能五态诊疗技术建设(2023PY-YS-29)
山西中医药管理局门氏中医功能态诊疗体系建设研究(2023ZYYA030)
中医临床基础学科基金(2023XKJS-04)。
关键词
护胃散
化疗性恶心和呕吐
网络药理学
作用机制
分子对接
Huwei Powder
chemotherapy-induced nausea and vomiting
network pharmacology
mechanism
molecular docking
