基于网络药理学和分子对接技术探究健脾化湿方治疗溃疡性结肠炎的作用机制  

Mechanism of Jianpi Huashi Formula in treatment of ulcerative colitis based on network pharmacology and molecular docking technology

作　　者：徐张扬 蒋蓓尔 万雨 闵天骄 刘光盛 何颖 Xu Zhangyang;Jiang Beier;Wan Yu;Min Tianjiao;Liu Guangsheng;He Ying(Marine Biomedicine and Polar Medicine Laboratory,Naval Medical Center,Shanghai 200433,China)

机构地区：[1]海军特色医学中心海洋生物医药与极地医学研究室,上海200433 [2]海军军医大学基础医学院 [3]上海海洋大学研究生院

出　　处：《海军医学杂志》2023年第9期935-942,共8页Journal of Navy Medicine

基　　金：海装军内科研重点项目(16A211)。

摘　　要：目的 利用网络药理学和分子对接技术探究健脾化湿方治疗溃疡性结肠炎(ulcerative colitis,UC)的作用机制。方法 通过文献检索和TCMSP、 Drugbank数据库筛选健脾化湿方的化学成分及潜在作用靶点。通过Genecards、 OMIM、 DisGeNet数据库获取UC相关靶点。利用R语言获得交集靶点,并通过Cytoscape软件和String数据库绘制“药物活性成分-疾病-靶点”网络互作图和蛋白相互作用(protein-protein interaction,PPI)网络互作图。利用R语言对交集靶点进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)进行富集分析,使用CentiScaPe和Cytohub插件获取网络中的关键活性成分和核心靶点,并将有效成分与核心靶点进行分子对接以验证结果的可靠性。结果 健脾化湿方治疗UC的有效成分共18个,靶点75个。潜在有效成分主要包括槲皮素、山柰酚、川陈皮素等,核心靶点包括白细胞介素6(interleukin-6,IL-6)、肿瘤坏死因子(tumor necrosis factor,TNF)、苏氨酸激酶1(AKT1)、肿瘤蛋白p53(TP53)等,主要涉及流体剪切应力与动脉粥样硬化信号通路、糖尿病并发症AGE-RAGE信号通路、TNF等信号通路。分子对接结果显示,薯蓣皂素,山柰酚,槲皮素,柚皮素与AKT1,TNF,IL-6等关键靶点均有较强的结合能力。结论 健脾化湿方通过多靶点、多通路协同作用发挥抗炎、抗氧化及免疫调节等作用,从而治疗UC。Objective To investigate the therapeutic effect and molecular mechanism of the Jianpi Huashi Formula on ulcerative colitis by network pharmacology and molecular docking technology.Methods TCMSP database,Drugbank database and information retrieval were used to screen the active components and potential targets of Jianpi Huashi Formula.The target genes related to ulcerative colitis were obtained from Genecards,OMIM and DisGeNet databases.The intersectional targets were obtained by R language.Cytoscape software and String database were used to construct and analyze the “drug-active ingredient-disease-targets” network and protein-protein interaction(PPI) network.R language was used for gene ontology(GO) analysis and Kyoto encyclopedia of genes and genomes(KEGG) enrichment analysis on the intersectional targets.CentiScaPe and Cytohub plug-in were used to identify the key active components and core targets,and then we performed molecular docking of main active ingredients and target proteins.Results A total of 18 active ingredients were found in Jianpi Huashi Formula,corresponding to 75 targets.The key active ingredients were quercetin,nobiletin,and kaempferol.The key proteins involved were interleukin-6(IL-6),tumor necrosis factor(TNF),threonine kinase 1(AKT1),and tumor protein P53(TP53).They were mainly enriched in the fluid shear stress and atherosclerosis signaling pathway,AGE-RAGE(advanced glycation end products-receptor for advanced glycation end products) signaling pathway in diabetic complications,and TNF signaling pathway.The molecular docking results showed that diosgenin,kaempferol,quercetin and naringin had strong binding activity with AKT1,TNF and IL-6.Conclusion Many active components of Jianpi Huashi Formula may play therapeutic roles in the treatment ulcerative colitis by regulating multiple targets and multiple signaling pathways in anti-inflammatory,antioxidant and immune regulation.

关 键 词：健脾化湿方 溃疡性结肠炎 网络药理学 分子对接 

分 类 号：R285[医药卫生—中药学]