摘要
目的基于网络药理学和分子对接技术研究阿拉坦五味丸治疗慢性胃炎的分子机制。方法通过TCMSP、BATMAN-TCM数据库和中国知网、维普、万方检索库确定阿拉坦五味丸活性成分,并从Swiss Targer Prediction、SEA、Pharm Mapper平台中预测活性成分相关靶点,在DisGeNET和GeneCard数据库中收集慢性胃炎相关靶点。将活性成分靶点与疾病靶点取交集,并构建“药物–活性成分–核心靶点”相互作用网络,利用STRING数据库构建蛋白相互作用(PPI)网络;应用Metascape数据库进行基因本体(GO)功能及京都基因与基因组百科全书(KEGG)通路富集分析;使用Auto Dock 4.2.6软件对阿拉坦五味丸的关键活性成分和PPI网络中的核心靶点进行分子对接,以评价其结合能力。结果共获得阿拉坦五味丸活性成分30个,治疗慢性胃炎的核心靶点106个。分析PPI网络获知肿瘤坏死因子(TNF)、白蛋白(ALB)、白细胞介素(IL)-6、蛋白激酶B1(Akt1)、血管内皮生长因子A(VEGFA)、表皮生长因子受体(EGFR)起主要作用。GO富集分析主要涉及对无机物的反应、磷酸化的正调控和细胞死亡的正调控等生物过程,蛋白激酶活性、蛋白激酶结合和蛋白酪氨酸激酶活性等分子功能,膜筏、薄膜侧面、囊泡腔及受体复合物等细胞组分。KEGG通路分析主要涉及癌症通路、癌症中的蛋白聚糖、糖尿病并发症中的糖基化终末产物-糖基化终产物受体(AGE-RAGE)信号通路等。分子对接结果显示,阿拉坦五味丸中五灵脂二萜酸、鞣花酸、槲皮素与关键靶点之间具有较好的亲和力。结论阿拉坦五味丸可能通过五灵脂二萜酸、鞣花酸、槲皮素等主要活性成分作用TNF、ALB、IL-6等靶点,可能通过参与癌症的发病途径、糖尿病并发症中的AGE-RAGE、低氧诱导因子-1(HIF-1)、磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)等信号通路有效治疗慢性胃炎。
Objective To study the molecular mechanism of Alatan Wuwei Pills in treatment of chronic gastritis based on network pharmacology and molecular docking technology.Methods To determine the active ingredients of Alatan Wuwei Pills through TCMSP,BATMAN-TCM databases,as well as CNKI,VIP,and Wanfang search databases.To predict active ingredient related targets from Swiss Targer Prediction,SEA,and Pharm Mapper platforms,and chronic gastritis related targets were collected from DisGeNET and GeneCard databases.Intersect the active ingredient target with the disease target,build an interaction network of“drugs–active ingredients–core targets”,using the STRING database to construct a PPI network,applying the Metascape database to analyze GO functions and KEGG pathway enrichment.Using the AutoDock 4.2.6 software to perform molecular docking on the key active ingredients of Alatan Wuwei Pills and the core targets in the PPI network to evaluate their binding ability.Results A total of 30 active ingredients were obtained from Alatan Wuwei Pills,and 106 core targets were identified for the treatment of chronic gastritis.Analyzing the PPI network reveals that TNF,ALB,IL-6,Akt1,VEGFA,and EGFR play a major role.GO enrichment analysis mainly involves reactions to inorganic substances,regulation of phosphorylation,regulation of cell death and other biological process,protein kinase activity,protein kinase binding,protein tyrosine kinase activity and other molecular function,membrane rafts,side of membrane,vesicle lumen,receptor complex and other cellular components.KEGG pathway analysis mainly involves cancer pathway,proteoglycan in cancer,AGE-RAGE signaling pathway in diabetes complications,etc.The molecular docking results showed that there was a good affinity between the diterpenoid acid,tannic acid,quercetin and key targets in Alatan Wuwei Pills.Conclusion Alatan Wuwei Pills may act on targets such as TNF,ALB,and IL-6 through the main active ingredients of wulingzhic acid,ellagic acid,quercetin etc,it may be through parti
作者
何祥
唐给斯
山丹
莫希叶勒
吴双英
HE Xiang;TANG Geisi;SHAN Dan;MOXI Yele;WU Shuangying(Hulunbeier Mongolian Medicine Hospital,Hulunberer 021000,China;College of Traditional Mongolian Medicine,Inner Mongolia University for Nationalities,Tongliao 028000,China)
出处
《现代药物与临床》
CAS
2024年第5期1145-1154,共10页
Drugs & Clinic
基金
呼伦贝尔市蒙医医院院级项目(YJ23-015)。
关键词
阿拉坦五味丸
慢性胃炎
网络药理学
分子对接
五灵脂二萜酸
鞣花酸
槲皮素
Alatan Wuwei Pills
chronic gastritis
network pharmacology
molecular docking
wulingzhic acid
ellagic acid
quercetin
