[关键词]
[摘要]
目的 基于网络药理学和分子对接技术探讨健脾祛湿方“异病同治”慢性腹泻和慢性疲劳综合征的作用 机制。方法 检索 TCMSP 数据库获取健脾祛湿方中中药活性成分,预测其作用靶点,利用 UniProt 数据库转 换靶点基因信息;应用 GeneCards 和 OMIM 数据库筛选两种疾病相关疾病靶点;利用 Venny 2.1.0 绘制韦恩图, 将获得的靶点蛋白与疾病靶点进行汇总取交集,获得三者共有靶点;导入 String 数据库构建核心靶点蛋白质相 互作用图,通过 Cytoscape 3.7.0 构建“单味中药-交集靶点-疾病”网络图;根据度值筛选健脾祛湿方治疗慢 性腹泻和慢性疲劳综合征的关键靶点基因,应用 David 数据库进行 GO 功能和 KEGG 通路富集分析,微生信平 台进行可视化处理;运用 AutoDock Tools-1.5.7 模拟活性成分与关键靶点分子对接,Pymol 软件结果可视化。 结果 筛选后得到健脾祛湿方有效成分 197 个,作用靶点 248 个,与两种疾病三者交集靶点 195 个;“单味药- 交集靶点-疾病”网络图获槲皮素、木犀草素、山柰酚、豆甾醇等 5 个主要活性成分;PPI 网络图中核心靶点为 细胞肿瘤抗原 p53(TP53)、丝氨酸/苏氨酸蛋白激酶(AKT1)、白细胞介素 6(IL6)等 6 个;GO 功能富集分析涉及 细胞组成(CC)106 项,分子功能(MF)166 项,生物过程(BP)829 项;KEGG 通路富集分析主要涉及 TNF、脂质与 动脉粥样硬化、人巨细胞病毒感染、糖尿病并发症中的 AGE-RAGE 信号、IL-17 信号等通路;分子对接结果表 明,各主要活性成分与靶点蛋白结合良好。结论 健脾祛湿方通过多种药物成分,调节多条信号通路,关联多 个关键靶点,从而发挥对慢性腹泻和慢性疲劳综合征的“异病同治”作用。
[Key word]
[Abstract]
Objective To explore the mechanism of Jianpi Qushi Recipe in the same treatment of chronic diarrhea and chronic fatigue syndrome based on network pharmacology and molecular docking technology. Methods TCMSP database was searched to obtain the active components of traditional Chinese medicine in Jianpi Qushi Recipe and predict its target. UniProt database was applied to convert target gene information. GeneCards and OMIM databases were used to screen disease-related targets. Venny2.1.0 was used to draw the Venn diagram,and the obtained target proteins and disease targets were summarized and intersected to obtain the common targets of the three. The common targets were imported into the String database to construct protein interaction map of the core targets,and the 'single Chinese herbal medicine-intersection targets-disease' network map was constructed by Cytoscape 3.7.0. The key target genes of Jianpi Qushi Recipe in the treatment of chronic diarrhea and chronic fatigue syndrome were screened according to the degree value. The GO function and KEGG pathway enrichment analysis were performed using the David database, and the micro-bioinformatics platform was visualized. AutoDock Tools-1.5.7 was used to simulate the docking of active components with key target molecules, and the results were visualized by Pymol software. Results After screening, 197 active components of Jianpi Qushi Recipe,248 acting targets,and 195 intersection targets of two diseases and acting targets were obtained. Five main active ingredients including quercetin,luteolin,kaempferol and stigmasterol were obtained from the network diagram of 'single herb-intersection targets-disease'. The core targets in the PPI network diagram were cell tumor antigen p53(TP53),serine/threonine protein kinase(AKT1),interleukin 6(IL6),and so on. GO functional enrichment analysis involved 106 items of CC,166 items of MF and 829 items of BP. KEGG pathway enrichment analysis mainly involved TNF,lipid and atherosclerosis,human cytomegalovirus infection,AGE-RAGE signaling and IL-17 signaling,etc in diabetic complications. The results of molecular docking showed that the main active components were well combined with the target proteins. Conclusion A variety of drug components of Jianpi Qushi Recipe can regulate multiple signaling pathways,associate multiple key targets,and play a therapeutic role in chronic diarrhea and chronic fatigue syndrome. Based on the confirmed drug data,the effective active components,proteinprotein interactions,core targets and signaling pathways of Jianpi Qushi Recipe were analyzed to further elucidate the mechanism of 'treating different diseases with the same treatment'.
[中图分类号]
R285. 5
[基金项目]
浙江省自然科学基金项目(LY21H270003);湖州市科技局重点项目(2023GZ87)