基于网络药理学-分子对接技术研究贞芪扶正颗粒治疗大肠癌相关性疲乏的作用机制

doi:10.3969/j.issn.1004-616x.2022.05.002

摘要/Abstract

摘要： 目的：探讨贞芪扶正颗粒治疗大肠癌相关性疲乏的作用机制。方法：通过中药系统药理学数据库与分析平台(TCMSP)获取黄芪、女贞子的主要化学成分及靶点，根据ADME筛选中药活性组分；通过GeneCards、OMIM等数据库获取大肠癌相关性疲乏的主要靶点，利用String平台进行蛋白质相互作用分析，构建蛋白互作网络(PPI)并使用CytoScape 3.7.2中的MCODE插件挖掘网络中潜在的蛋白质功能模块。采用Metascape平台分析“药物-成分-靶点”及其参与的生物过程及通路，然后采用Cytoscape 3.7.2软件构建“贞芪扶正颗粒成分-大肠癌相关性疲乏靶点-通路”网络，最后通过AutoDock Vina1.1.2进行分子对接验证。结果：贞芪扶正颗粒治疗大肠癌相关性疲乏的核心活性成分为槲皮素、木犀草素、山柰酚、β-谷甾醇、毛蕊异黄酮等，核心靶点有 AKT1、JUN、MMP9、VEGFA等，分子对接结果亦证明以上核心成分与核心靶点结合活性较好。贞芪扶正颗粒治疗大肠癌相关性疲乏的生物学通路主要作用于癌症通路、PI3K-AKT信号通路等。结论：贞芪扶正颗粒治疗大肠癌相关性疲乏的机制具有多成分、多靶点、多通路的特点，本研究为进一步研究贞芪扶正颗粒治疗大肠癌相关性疲乏的机制及临床应用提供了依据。

关键词: 大肠癌, 癌因性疲乏, 贞芪扶正颗粒, 网络药理学, 槲皮素, 癌症通路

Abstract: OBJECTIVE: To explore mechanisms of Zhenqi Fuzheng granules in the treatment of colorectal cancer-related fatigue.METHODS: The main chemical components of Astragalus membranaceus and Ligustrum lucidum were obtained from the traditional Chinese medicine system pharmacology database and analysis platform (TCMSP),and the active components of Chinese medicine were screened according to ADME.The main targets of colorectal cancer-related fatigue were obtained through databases such as GeneCards and OMIM.The protein interaction analysis was carried out by using String platform,and the protein-protein interaction network (PPI) was constructed.The MCODE plug-in in CytoScape 3.7.2 was used to mine the potential protein function modules in the network.Metascape platform was used to analyze"drugs-componentstargets "and their biological processes and pathways involved,and then Cytoscape 3.7.2 software was used to construct a network of" Zhenqi Fuzheng Granules-colorectal cancer-related fatigue targets-pathways".Finally,the molecular docking was verified by AutoDock Vina1.1.2.RESULTS: The core active components of Zhenqi Fuzheng granules in the treatment of colorectal cancer-related fatigue were quercetin,luteolin,kaempferol,β-sitosterol and stamen isoflavones,and the core targets were AKT1,JUN,MMP9,VEGFA and so on.The results of molecular docking also proved that the above core components had good binding activity to the core targets.The biological pathway of Zhenqi Fuzheng granules in the treatment of colorectal cancer-related fatigue mainly acts on pathways in cancer,PI3K-AKT signaling pathway and so on.CONCLUSION: This study indicated the multi-component,multi-target and multi-pathway characteristics of Zhenqi Fuzheng granules in the treatment of colorectal cancer-related fatigue,and provided a basis for further research on the mechanism and clinical application of Zhenqi Fuzheng granules in the treatment of colorectal cancer-related fatigue.

Key words: colorectal cancer, cancer-related fatigue, Zhenqi Fuzheng granules, network pharmacology, quercetin, pathways in cancer

中图分类号:

R285.5

程艳野, 习弯弯, 毛雪杨, 魏天怡, 胡海瑞, 李志刚. 基于网络药理学-分子对接技术研究贞芪扶正颗粒治疗大肠癌相关性疲乏的作用机制[J]. 癌变·畸变·突变, 2022, 34(5): 335-343.

CHENG Yanye, XI Wanwan, MAO Xueyang, WEI Tianyi, HU Hairui, LI Zhigang. A network pharmacologymolecular docking study on mechanisms of Zhenqi Fuzheng granules on colorectal cancerrelated fatigue[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2022, 34(5): 335-343.

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