基于网络药理学与分子对接探讨枳术丸对非酒精性脂肪性肝病的作用机制  

Exploring the action mechanism of Zhizhu Wan in treating non-alcoholic fatty liverbased on network pharmacology and molecular docking

作　　者：韦琴英 王振常 WEI Qinying

机构地区：[1]广西国际壮医医院,广西南宁530001

出　　处：《中医临床研究》2024年第29期1-8,共8页Clinical Journal Of Chinese Medicine

基　　金：国家自然科学基金项目(81960910);2023年广西中医药多学科交叉创新团队项目(GZKJ2311);广西中医药重点学科中医肝胆病学学科项目(GZXK-Z-20-06)。

摘　　要：目的:通过网络药理学和分子对接技术研究枳术丸在治疗非酒精性脂肪性肝病(Non-Alcoholic Fatty Liver Disease,NAFLD)可能的作用靶点和机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)筛选出枳术丸的活性成分及其对应的靶点。采用Disgenet、GeneCards及OMIM数据库预测NAFLD相关靶点,聚焦共同靶标,得到枳术丸治疗NAFLD的关键靶点,将已确认的关键靶点输入STRING数据库进行分析,构建蛋白质-蛋白质相互作用网络,并通过Cytoscape 3.8.0软件可视化。采用Metascape数据库对关键靶点进行基因本体论(GO)功能及京都基因与基因组百科全书(KEGG)通路富集分析。通过AutoDock Vina进行分子对接验证,利用PyMOL软件对结合能较低的结果进行可视化展示。结果:共获得枳术丸靶点125个、NAFLD靶点1 506个,药物、疾病共同靶点51个,核心靶点有丝氨酸/苏氨酸蛋白激酶1、肿瘤蛋白p53、肿瘤坏死因子、白细胞介素-6,可能通过IL-17、磷脂酰肌醇3激酶-蛋白激酶B、缺氧诱导因子-1信号通路等作用于NAFLD。分子对接结果显示核心靶点与药物成分之间亲和力较强。结论:通过这些研究可初步了解到枳术丸治疗NAFLD的重要活性成分和可能的作用方式,为药物效能、作用机制及实际应用等的进一步研究提供科学依据。Objective:To investigate the potential targets and action mechanisms of Zhizhu Wan(枳术丸)in the treatment of non-alcoholic fatty liver disease(NAFLD)through network pharmacology and molecular docking technology.Methods:The active ingredients and corresponding targets of Zhizhu Wan were screened through the TCMSP database.Disgenet,GeneCards,and OMIM databases were used to predict NAFLD related targets.Focusing on common targets,key targets of Zhizhu Wan on NAFLD were obtained.The confirmed key targets were inputted into the STRING database to construct a protein-protein interaction network,which was visualized by Cytoscape 3.8.0 software.In Metascape database,the gene ontology(GO)analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis for key targets were performed.Molecular docking validation was performed by AutoDock Vina,and results with lower binding energies were visualized by PyMOL software.Results:There were 125 targets of Zhizhu Wan,1506 targets of NAFLD,and 51 common targets of drug and disease.The core targets included Akt serine/threonine kinase 1(AKT1),tumor protein p53(TP53),tumor necrosis factor(TNF),and interleukin(IL)-6,which might act on NAFLD by IL-17,phosphatidylinositol 3 kinase/protein kinase B(PI3K-Akt)and hypoxia inducible factor-1(HIF-1)signaling pathways.The molecular docking results showed a strong affinity between the core target and the drug components.Conclusion:Through these studies,the important active components and possible modes of action of Zhizhu Wan on NAFLD can be preliminary understood,and scientific basis for further research on drug efficacy,action mechanism,and practical application can be provided.

关 键 词：枳术丸 非酒精性脂肪性肝病 网络药理学 分子对接 

分 类 号：R256.4[医药卫生—中医内科学]