摘要
采用网络药理学和分子对接技术揭示甘草(Glycyrrhiza uralensis)有效成分对大肠杆菌(Escherichia coli)的抑菌机制,并通过体外抑菌实验进行验证。TCMSP数据库用于获取甘草主要活性成分及其对应靶点,通过GeneCards和OMIM数据库获取抑制大肠杆菌靶点,利用jvenn在线平台获得交集靶点。采用STRING平台进行交集靶点蛋白互作网络分析,以Metascape平台进行GO功能富集和KEGG通路富集分析。获取抑制5种致病性大肠杆菌的交集靶点后,通过分子对接和体外抑菌实验验证甘草抑制致病性大肠杆菌的主要活性成分。筛选共得到86个活性成分和93个交集靶点。GO和KEGG富集分析表明甘草主要通过对外源刺激的反应和细菌源分子的反应等生物过程以及通过癌症通路、脂质和动脉粥样硬化等通路实现对大肠杆菌的抑制。抑制5种致病性大肠杆菌关键靶点为IL6、TP53和STAT3,分子对接结果显示柚皮素、异芒柄花素和3″-甲氧基光甘草定与以上靶点亲和力较高。上述3种活性成分对5种致病性大肠杆菌的最小抑菌浓度分别为0.16~0.31、0.62~1.25、0.07~0.16μg/mL,最小杀菌浓度分别为0.16~0.62、1.25~2.50、0.16~0.31μg/mL,3″-甲氧基光甘草定抑菌效果最好。该研究为探究甘草抑制大肠杆菌的机制及发掘甘草中抑制致病性大肠杆菌的关键成分提供了基础。
This study used network pharmacology and molecular docking technology to explore the inhibitory mechanism of active ingredients in Glycyrrhiza uralensis on pathogenic Escherichia coli and verified by in vitro bacteriostatic test.The active ingredients and targets of G.uralensis were screened in TCMSP databases.Genecards and OMIM databases were searched for targets that inhibit E.coli.The jvenn platform was used to obtain intersection targets.The protein-protein interaction(PPI)analysis of the intersection targets was performed using the STRING platform,followed by GO function and KEGG pathway enrichment analyses using the Metascape platform.After obtaining the key targets inhibiting 5 pathogenic E.coli,the effect of primary active ingredients was identified by molecular docking and in vitro bacteriostatic test.After screening,86 active ingredients and 93 intersection targets were obtained.Through GO and KEGG enrichment analysis,G.uralensis mainly affected biological processes such as response to xenobiotic stimulus and response to molecule of bacterial origin,and pathways like pathways in cancer,lipid and atherosclerosis pathways.Key targets for inhibiting 5 pathogenic E.coli were IL6,TP53,and STAT3,and molecular docking showed that the naringenin,isoformononetin,and 3″-methoxyglabridin exhibited high binding energy to these targets.The minimal inhibit concentration of above 3 active ingredients against 5 pathogenic E.coli varied between 0.16-0.31,0.62-1.25,and 0.07-0.16μg/mL,respectively,and minimum bactericidal concentration varied between 0.16-0.62,1.25-2.50,and 0.16-0.31μg/mL,respectively.3″-Methoxyglabridin displayed the best antibacterial activity.This study provides the basis for exploring the mechanism of G.uralensis in inhibiting E.coli and key active ingredients in G.uralensis for inhibiting pathogenic E.coli.
作者
杨秉乾
恽辰珂
刘蕾
陈天翼
李冰峰
张森
常思源
YANG Bingqian;YUN Chenke;LIU Lei;CHEN Tianyi;LI Bingfeng;ZHANG Sen;CHANG Siyuan(Bio-based Platform Chemicals Catalysis Engineering Technology Research and Development Center of Jiangsu Province,Nanjing Polytechnic Institute,Nanjing 210048,China;Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization,Nanjing University of Chinese Medicine,Nanjing 210023,China)
出处
《食品与发酵工业》
北大核心
2025年第20期122-130,I0001,I0002,共11页
Food and Fermentation Industries
基金
国家自然科学基金项目(221006073)
中国石油和化学工业联合会责任关怀专项研究课题(2022CRCB004)
江苏省高职院校教师专业带头人高端研修项目(2023GRFX038)
江苏省研究生实践创新计划项目(SJCX23_0766)
江苏省青蓝工程。
关键词
网络药理学
甘草
致病性大肠杆菌
分子对接
体外抑菌实验
network pharmacology
Glycyrrhiza uralensis
pathogenic Escherichia coli
molecular docking
in vitro bacteriostatic test
