基于网络药理学及分子对接技术构建中药复方调控网络模型探讨痛泻要方加味治疗溃疡性结肠炎的作用机制

Discussion on the Network Model of TCM Compound Regulation Based on Network Pharmacology and Molecular Docking Technology Effect Mechanism of Tongxie Yaofang Adds Flavor on Ulcerative Colitis

目的:基于网络药理学,结合分子对接技术,来探讨痛泻要方加味对溃疡性结肠炎(UC)产生治疗作用的物质基础及分子机制。方法:通过TCMSP数据库搜索痛泻要方加味所包含的全部化学成分及作用靶点,利用Genecards、OMIM、TTD及DrugBank 4个数据库获取UC的受体靶点,制作Venny图寻找药物和疾病的共有靶点;结合Cytoscape软件对中药复方调控网络进行可视化展示;在STRING数据库中寻找靶点蛋白图并构建网络核心;分析GO生物学过程和KEGG富集通路;并对核心蛋白进行3D结构的重建,实现Vina分子对接。结果:在TCMSP中获得痛泻要方加味的有效活性成分共98个,成分靶点231个,疾病基因4 635个,二者共有基因161个;GO生物学过程主要涉及对脂多糖、抗生素、细菌来源分子、营养水平、氧化应激、活性氧、类固醇激素等反应,与细胞周期蛋白依赖性蛋白激酶等全酶复合物、转录因子等的活性、RNA聚合酶II特异性及磷酸酶等酶的结合有关;KEGG富集分析:与类固醇激素、精氨酸生物的合成,色氨酸、精氨酸、谷胱甘肽和脯氨酸代谢密切相关;黄芩甙元、山奈酚等成分可与AKT1蛋白受体进行高效对接,构象稳定。结论:痛泻要方加味成分复杂,对UC的治疗作用具有靶点多样、通路复杂、层次分明的特点;AKT1等重点因子可作为治疗UC疗效的重要观测指标,为下一步临床验证奠定基础。

Objective:Based on network pharmacology and molecular docking technology,to explore the material basis and molecular mechanism of Tongxie Yaofang adds flavor on the therapeutic effect of ulcerative colitis.Methods:The TCMSP database was used to search all the chemical components and targets of Tongxie YaoFang,and the four databases of Genecards,OMIM,TTD and DrugBank were used to obtain the receptor targets of UC,and the Venny diagram was made to find the common targets of drugs and diseases.Combined with Cytoscape software,the regulation network of TCM compounds was sorted out and visualized.The protein map of target was found in the STRING database,and the network core was constructed.The GO biological process and KEGG enrichment pathway were analyzed.The 3D structure of the core protein was reconstructed to achieve Vina molecular docking.Results:A total of 98 active components,231 component targets and 4635 disease genes were obtained from the TCMSP,including 161 genes in total.The biological process of GO mainly involves the reactions to lipopolysaccharides,antibiotics,bacteria-derived molecules,nutrient levels,oxidative stress,reactive oxygen species,steroid hormones,etc.,and is related to the activity of holoenzyme complexes such as cyclin-dependent protein kinases,transcription factors,and the binding of enzymes such as RNA polymerase II and phosphatase.KEGG enrichment analysis:It is closely related to the biosynthesis of steroid hormones and arginine,metabolism of tryptophan,arginine,glutathione and proline.Baicalein,Kaempferol and other components can efficiently dock with AKT1 protein receptor,and the conformation is stable.Conclusions:Tongxie Yaofang flavored-adding ingredients are complex,and its therapeutic effects on UC are characterized by diverse targets,complex pathways and distinct levels.AKT1 can be used as an important observation index affecting the efficacy of UC,laying a foundation for the next clinical verification.