基于通降和胃法与网络药理学方法探讨半夏-枳实-黄连干预慢性胃炎的作用机制

The Intervention Effects of Banxia-Zhishi-Huanglian on Chronic Gastritis Based on Tongjiang Hewei Method and Network Pharmacology Method

目的:总结沈舒文教授通降和胃法辨治慢性胃炎(chronic gastritis,CG)的经验,基于网络药理学方法和分子对接技术对探讨半夏-枳实-黄连角药治疗CG平调寒热,升降气机的作用机制。方法:运用TCMSP、ETCM、BATMAN等数据库筛选半夏-枳实-黄连相关靶点,建立药物靶点数据库;通过CTD、DisGenet、GeneCards数据库筛选CG潜在靶点;利用Venny 2.1对药物靶点和疾病靶点进行映射,通过STRING平台构建交集靶点PPI网络;运用ClusterProfiler程序包进行基因本体(gene ontology,GO)功能富集分析和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)富集分析;利用Cytoscape 3.7.0构建“药物-潜在靶标-信号通路”网络关系图;通过Discovery Studio 2016软件对核心药效物质和受体蛋白进行分子对接分析。结果:沈舒文教授应用半夏-枳实-黄连角药通过寒热平调通降法辨治CG寒热互结、胃失和降证,效果良好。筛选得到药物靶点黄连165个,半夏84个,枳实114个,CG潜在靶点324个。活性成分通过作用于诱导型前列腺素内过氧化物合酶(prostaglandin-endoperoxide synthase 2,PTGS2)、过氧化物酶体增生激活受体γ(peroxisome proliferative activated receptor gamma,PPARG)和B淋巴细胞瘤(B-cell lymphoma-2,Bcl-2)等80个靶点发挥作用;靶点主要通过对氧化合物反应、对脂质反应和活性氧代谢正调控等方面参与流体剪切应力和动脉粥样硬化、AGE-RAGE、白细胞介素17(interleukin-17,IL-17)等信号通路。活性成分与关键靶点之间结合具有良好的亲和力。结论:半夏-枳实-黄连角药中柚皮苷、β-谷甾醇、豆甾醇、异橙黄酮等活性成分通过PTGS2、PPARG和BCL-2等靶点作用于流体剪切应力和动脉粥样硬化、AGE-RAGE和IL-17等信号通路,通过多组分、多靶标、多通路发挥治疗CG的作用。

Objective:To sum up professor Shen Shuwen's experience in differentiating and treating chronic gastritis(CG)by Tongjiang Hewei method,and discuss the mechanism of Banxia-Zhishi-Huanglian in the treatment of CG by mildly regulating cold and heat,adjusting Qi movement based on network pharmacology and molecular docking technology.Methods:TCMSP,ETCM and BATMAN databases were used to screen the targets related to Banxia-Zhishi-Huanglian,and to establish the data of herbal targets;CTD,DisGenet and GeneCards were used to screen the potential targets of CG;Venny 2.1 was applied to perform the mapping of herbal targets and disease targets,the intersection targets were used to build PPI network through STRING platform;ClusterProfiler software package was utilized to carry out enrichment analysis of GO function and KEGG pathway;Cytoscape 3.7.0 was used to construct the network diagram of“medicine-potential targets-signal pathway”;molecular docking analysis of the core pharmacodynamic substances and receptor protein was performed using Discovery Studio 2016 software.Results:Professor Shen Shuwen applied the method of mildly regulating cold and heat,adjusting Qi movement to differentiate and treat CG of intermingling cold with heat,stomach Qi rising with the good effects of Banxia-Zhishi-Huanglian.By screening,165 Huanglian targets,84 Banxia ones,114 Zhishi ones and 324 CG potential targets were yielded.The active ingredients could play a role through acting on 80 targets including PTGS2,PPARG and Bcl-2;the targets,mainly involving the reaction to the oxygen compounds,lipid response and positive regulation of reactive oxygen species metabolism,participate in signal pathway such as fluid shear stress and atherosclerosis,AGE-RAGE,and interleukin 17(IL-17).Binding between the active ingredients and key targets have good affinity.Conclusion:The active ingredients such as Naringin,β-sitosterol,myristerol and isoorange flavonoids contained in Banxia-Zhishi-Huanglian act on signal pathways including fluid shear stress and atherosclerosis,AGE-RAGE,and IL-17,which could play a role in treating CG through many components,many targets and pathways.