文献类型：期刊文献

中文题名：基于网络药理学和分子对接技术探讨黄芪经铁死亡途径治疗结直肠癌前病变的作用机制

英文题名：Exploration of the mechanism of Radix Astragali in treating precancerous lesions of colorectal cancer via ferroptosis based on network pharmacology and molecular docking techniques

作者：王蒙[1,2];宁月[1,2];邵利华[1,2];韩静[3];李海龙[3];赵雪灵[4]

第一作者：王蒙

机构：[1]甘肃中医药大学第一临床医学院,甘肃兰州730101;[2]甘肃省中药新产品创制工程实验室,甘肃省中医方药挖掘与创新转化重点实验室,甘肃兰州730000;[3]甘肃中医药大学附属医院科研管理科,甘肃兰州730020;[4]甘肃中医药大学附属医院检验科,甘肃兰州730020

第一机构：甘肃中医药大学临床医学院

年份：2025

卷号：42

期号：1

起止页码：45

中文期刊名：甘肃中医药大学学报

外文期刊名：Journal of Gansu University of Chinese Medicine

基金：甘肃中医药大学科学研究与创新基金项目(2019KCZD-5);甘肃省卫生健康行业科研计划项目(GSWSKY2022-25)。

语种：中文

中文关键词：结直肠癌前病变;黄芪;网络药理学;分子对接;作用机制

外文关键词：precancerous lesions of colorectal cancer;Radix Astragali;network pharmacology;molecular docking;mechanism of action

摘要：目的基于网络药理学和分子对接技术探讨黄芪经铁死亡途径治疗结直肠癌前病变的作用机制。方法采用中药系统药理学数据库与分析平台(TCMSP)获取黄芪的主要活性成分及靶点;通过在线人类孟德尔遗传(OMIM)数据库、疗效药靶数据库(TTD)、GeneCards和DrugBank数据库获取结直肠癌前病变、铁死亡的主要作用靶点;通过微生信网站得到黄芪与铁死亡、结直肠癌、结直肠癌前病变的共同靶点;用Metascape平台分析药物-成分-靶点及交集靶点参与的生物过程(BP),运用Cytoscape3.8.0软件构建活性成分-靶点-通路网络图,并使用AutoDock对关键靶点与相应活性成分进行分子对接验证。结果从黄芪中筛选得到13种主要活性成分,并得到黄芪与铁死亡、结直肠癌、结直肠癌前病变的共同靶点33个,与结直肠癌前病变有关的核心活性成分为槲皮素、山奈酚、芒柄花黄素、异鼠李素、7-O-甲基异木糖醇等,关键靶点为肿瘤蛋白53(TP53)、米克基因(MYC)、原癌基因(JUN)、磷酸酶张力蛋白同源物(PTEN)、低氧诱导因子-1α(HIF-1α)等;分子对接结果显示,筛选的主要活性成分与对应靶点具有良好的结合活性。结论黄芪可能通过槲皮素、山奈酚、芒柄花黄素、异鼠李素、7-O-甲基异木糖醇等主要活性成分作用于TP53、MYC、JUN、PTEN、HIF-1α等相关靶点,通过调控炎症、细胞凋亡、自噬等,经铁死亡途径发挥治疗结直肠癌前病变的作用。
Objective To explore the action mechanism of Radix Astragali in treating precancerous lesions of colorectal cancer through the ferroptosis pathway based on network pharmacology and molecular docking techniques.Methods The main active components and targets of Radix Astragali were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP).The main targets of precancerous lesions of colorectal cancer and ferroptosis were obtained from the online mendelian inheritance in man(OMIM)database,therapeutic target database(TTD),GeneCards and DrugBank.The common targets of Radix Astragali with ferroptosis,colorectal cancer,and precancerous lesions of colorectal cancer were obtained from the microbioinformatics website.The biological processes(BP)involved in the drug-component-target and intersection targets were analyzed using the Metascape platform.The active component-target-pathway network diagram was constructed using Cytoscape3.8.0 software,and molecular docking was performed using AutoDock to verify the binding activity of the key targets and corresponding active components.Results 13 main active components of Radix Astragali and 33 common targets with ferroptosis,colorectal cancer,and precancerous lesions of colorectal cancer were screened and obtained.The core active components related to precancerous lesions of colorectal cancer were quercetin,kaempferol,formononetin,isorhamnetin,and 7-O-methyl isoxylitol,and the key targets were tumor protein 53(TP53),myc proto-oncogene(MYC),jun proto-oncogene(JUN),phosphatase and tensin homolog(PTEN),and hypoxia-inducible factor-1α(HIF-1α).Molecular docking results showed that the main active components screened had good binding activity with the corresponding targets.Conclusion Radix Astragali may exert therapeutic effects on precancerous lesions of colorectal cancer through the ferroptosis pathway by acting on TP53,MYC,JUN,PTEN,HIF-1α,and other related targets via quercetin,kaempferol,formononetin,isorhamnetin,and 7-O-methyl isoxylitol,and by regulating inflammation,apoptosis,autophagy,etc.