基于网络药理学和分子对接技术探究首乌藤的潜在肝毒性机制  

Potential hepatotoxic mechanism of Polygoni multiflori caulis based upon network pharmacology and molecular docking technology

作　　者：谈泽烨 周桂 丰依明 项楠 陈灵如 谢瑞芳[1] 周昕[1] TAN Zeye;ZHOU Gui;FENG Yiming;XIANG Nan;CHEN Lingru;XIE Ruifang;ZHOU Xin(Department of Pharmacy,Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China)

机构地区：[1]上海中医药大学附属龙华医院药学部,上海200032

出　　处：《中国医院药学杂志》2024年第23期2731-2736,共6页Chinese Journal of Hospital Pharmacy

基　　金：上海市中医药传承创新发展三年行动计划项目[编号:ZY(2021-2023)-0203-1];上海市科技计划项目(编号:20S2901400)。

摘　　要：目的:通过网络药理学及分子对接技术探究首乌藤的潜在肝毒性机制。方法:根据文献数据,利用TCMSP、TCMID、HIT等数据库检索首乌藤主要活性成分以及相关靶点、药物性肝损的疾病靶点。对首乌藤靶点及疾病靶点进行交集分析,得核心交集靶点。利用核心交集靶点信息进行蛋白互作网络分析、KEGG及GO富集分析。采用AutoDock 1.5.7版进行分子对接,并应用PyMOL软件对对接结果进行可视化示例;最后利用体外试验、毒理数据库以及体内试验对筛选出的结果进行初步验证。结果:网络药理学确定首乌藤可以结合BCL2和EGFR等靶点通过癌症信号通路、PI3K-AKT等信号通路导致药物性肝损,大黄酚、大黄素和大黄素甲醚苷为重要活性成分。分子对接结果显示活性成分与核心靶点之间的结合力较稳定。体外验证试验结果表明大黄素与大黄素甲醚苷具有细胞毒性,体内验证试验表明大黄素存在一定的潜在肝毒性,与网药筛选结果一致。结论:应用网络药理学及分子对接技术对首乌藤致肝毒成分、机制、靶点、通路进行了初步探索,为进一步对首乌藤的临床应用研究和效应机制提供数据支持。OBJECTIVE To explore the potential hepatotoxic mechanism of Polygoni multiflori caulis(PMC)through network pharmacology and molecular docking techniques.METHODS Based upon the literature data,the relevant databases of TCMSP,TCMID and HIT were searched for identifying the major active ingredients of PMC,as well as target proteins associated with drug-induced liver injury(DILI).Intersection analysis of PMC/DILI targets was performed for acquiring core intersecting targets.Protein-protein interaction network,KEGG pathway and GO enrichment analyses were performed with information from core intersecting targets.Molecular docking was performed with AutoDock version 1.5.7.And the docking results were visualized with PyMOL software.Finally,the results were preliminarily validated through in vitro experiments,toxicology databases and in vivo experiments.RESULTS Network pharmacology indicated that PMC could interact with targets such as BCL2 and EGFR,leading to DILI through cancer and PI3K-AKT signaling pathways,etc.Important active ingredients included emodin,chrysophanol and chrysophanol-8-O-β-D-glucopyranoside.Molecular docking results showed stable binding affinity between active ingredients and core targets.In vitro validation assays demonstrated cytotoxicity of emodin and physcion-8-O-β-Dglucoside.And in vivo validation assays revealed potential hepatotoxicity of emodin consistent with the screening results of network pharmacology.CONCLUSION Network pharmacology and molecular docking techniques are applied for a preliminary exploration of the components,mechanisms,targets and pathways of PMC-induced liver injury,providing data supports for further clinical application researches and elucidating the underlying mechanisms.

关 键 词：首乌藤 药物性肝损 网络药理学 分子对接 

分 类 号：R966[医药卫生—药理学]