基于网络药理学与分子对接探讨舒肝宁注射液治疗非酒精性脂肪性肝病的潜在作用机制  

Exploration of potential mechanisms of Shuganning injection for non-alcoholic fatty liver disease through network pharmacology and molecular docking

作　　者：卢存存 王海博 柯立鑫 张强[4] LU Cuncun;WANG Haibo;KE Lixin;ZHANG Qiang(Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences,Beijing 100700,P.R.China;Department of Critical Care Medicine,Affiliated Hospital of Gansu University of Chinese Medicine,Lanzhou,Gansu 730000,P.R.China;Department of Pediatrics,Medical Center of University of Groningen,Groningen 9713GZ,Netherlands;Department of Gastroenterology,the First Affiliated Hospital of Henan University of CM,Zhengzhou,Henan 450000,P.R.China)

机构地区：[1]中国中医科学院中医临床基础医学研究所,北京100700 [2]甘肃中医药大学附属医院重症医学科,兰州730000 [3]格罗宁根大学医学中心儿科学实验室,荷兰格罗宁根9713GZ [4]河南中医药大学第一附属医院脾胃肝胆科,郑州450000

出　　处：《华西医学》2024年第12期1911-1916,共6页West China Medical Journal

基　　金：河南省中医药科学研究专项课题(2024ZY2046)。

摘　　要：目的利用网络药理学和分子对接技术探讨舒肝宁注射液治疗非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)的潜在作用机制。方法2024年5月23日—28日通过检索多个公共数据库收集舒肝宁注射液活性成分及其作用靶点、NAFLD相关疾病靶点的信息,进行蛋白相互作用网络分析、通路富集分析等。构建舒肝宁注射液治疗NAFLD的“中药-成分-靶点-疾病”多层次网络,并对“核心靶点-活性成分”网络中的度中心性评分排名前5位的关键活性成分与核心作用靶点进行分子对接。结果最终获得舒肝宁注射液的140个活性成分及其486个潜在作用靶点,得到1058个NAFLD相关靶点和舒肝宁注射液治疗NAFLD的154个共有靶点。共有靶点蛋白相互作用网络的拓扑分析筛选出包括蛋白激酶B1、过氧化物酶体增殖物激活受体α、过氧化物酶体增殖物激活受体γ、甾醇调节元件结合蛋白1、白细胞介素-6和基质金属蛋白酶-9等的16个关键作用靶点蛋白。其基因本体富集分析显示,共涉及179个生物学过程、13个细胞组分和48个分子功能;京都基因与基因组数据库富集分析显示,共涉及癌症、脂质与动脉粥样硬化、NAFLD和胰岛素抵抗等99条通路。构建的“中药-成分-靶点-疾病”多层次网络由102个节点和208条边组成。分子对接结果显示,黄芩苷、刺槐黄素、谷甾醇、β-谷甾醇和灵芝酸A这5个关键活性成分与核心作用靶点蛋白的亲和力均较高。结论舒肝宁注射液可能通过黄芩苷、刺槐黄素、谷甾醇、β-谷甾醇和灵芝酸A等成分作用于蛋白激酶B1、过氧化物酶体增殖物激活受体α、过氧化物酶体增殖物激活受体γ、甾醇调节元件结合蛋白1、白细胞介素-6和基质金属蛋白酶-9等关键靶点蛋白,参与调控脂质与动脉粥样硬化、NAFLD和胰岛素抵抗等通路,从而对NAFLD发挥治疗作用。Objective To explore the potential mechanism of Shuganning injection for non-alcoholic fatty liver disease(NAFLD)through network pharmacology and molecular docking techniques.Methods Information on the active compounds of Shuganning injection and their target proteins,as well as disease-related targets of NAFLD,were collected from multiple public databases from May 23rd to 28th,2024,for protein interaction network analysis and pathway enrichment analysis.A multi-level network of“herb-compound-target-disease”of Shuganning injection for NAFLD was constructed.Molecular docking was performed on the top 5 key active compounds ranked in the degree centrality of the“core target-active compound”network and the core action targets.Results Finally,140 active compounds of Shuganning injection and 486 potential targets,1058 NAFLD-related targets,154 common targets for NAFLD and Shuganning injection were obtained.Topological analysis of the common target protein interaction network identified 16 key target proteins of protein kinase B1,peroxisome proliferator-activated receptor alpha,peroxisome proliferator-activated receptor gamma,sterol regulatory element-binding protein 1,interleukin-6,and matrix metalloproteinase-9,etc.The gene ontology enrichment analysis showed that their genes were involved in 179 biological processes,13 cellular components,and 48 molecular functions.The Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that their genes were involved in 99 pathways of cancer,lipid and atherosclerosis,NAFLD and insulin resistance,etc.The constructed multi-level network of“herb-compound-target-disease”consisted of 102 nodes and 208 edges.The molecular docking results showed that the 5 key active compounds of baicalin,acacetin,sitosterol,β-sitosterol,and ganoderic acid A had high affinity for the core target proteins.Conclusion Shuganning injection may exert therapeutic effects on NAFLD through active compounds like baicalin,acacetin,sitosterol,β-sitosterol and ganoderic acid A,acting on key

关 键 词：网络药理学 分子对接 舒肝宁注射液 黄芩苷 作用机制 

分 类 号：R285[医药卫生—中药学]