[关键词]
[摘要]
目的 通过网络药理学与分子对接技术,筛选海藻的活性成分作为靶点和疾病靶点,建立“成分–靶点–疾病”网络,探讨海藻治疗糖尿病肾病的作用机制。方法 借助TCMSP数据库对海藻活性成分进行检索,从而获取其具体成分以及与之对应的靶蛋白,整合GeneCards数据库收集糖尿病肾病的与之相关联的作用靶点,并采用Venny交集分析方法鉴定海藻活性化合物与糖尿病肾病的靶点的共同作用靶标;使用STRING数据库挖掘化合物相关靶点的蛋白互作网络(PPI)关系图,基于Metascape数据库开展基因本体(GO)和京都基因和基因组百科全书(KEGG)通路富集研究。结果 鉴定出4个潜在活性成分,筛选获得137个候选靶点及259条关联通路,GO和KEGG富集分析揭示,海藻的生物活性主要通过干预调控内分泌抵抗,癌症通路以及磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B1(Akt)信号通路相关通路等。结论 海藻治疗糖尿病肾病的药理效应主要源于其对PI3K/Akt通路的调节作用,这种调节机制能够极为明显地提升胰岛素的敏感度,有力推动葡萄糖被细胞摄取,促进其代谢过程,并且有效控制血糖水平,从而间接保护肾脏功能。
[Key word]
[Abstract]
Objective To screen the active components of Sargassum and disease targets through network pharmacology and molecular docking technology, to establish “component-target-disease” network to explore the mechanism of Sargassum-Glycyrrhizae Radix in treatment of diabetic nephropathy. Methods To search the active ingredients of Sargassum by TCMSP database, so as to obtain their specific components and corresponding target proteins. To collect the action targets associated with diabetes nephropathy by GeneCards database, and to identify the common action targets of Sargassum active compounds and diabetes nephropathy targets by Venny intersection analysis. To mine PPI relationship diagrams of compound related targets by using STRING database, and conduct GO and KEGG pathway enrichment studies based on Metascape database. Results Four potential active components were identified, and 137 candidate targets and 259 associated pathways were screened. GO and KEGG enrichment analysis revealed that the biological activity of seaweeds mainly intervened and regulated endocrine resistance, cancer pathways, and PI3K/ Akt signaling pathway-related pathways. Conclusion The pharmacological effect of Sargassum on diabetes nephropathy is mainly due to its regulatory effect on PI3K/Akt pathway. This regulatory mechanism can significantly enhance insulin sensitivity, effectively promote glucose uptake by cells, promote its metabolic process, and effectively control blood glucose levels, thus indirectly protecting renal function.
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[基金项目]
内蒙古自治区自然科学基金项目(2023QN08031);内蒙古民族大学博士科研启动基金项目(BS622);内蒙古自治区本级事业单位引进人才科研启动资金(RCQD202208);内蒙古自治区高等学校科学研究项(NJZY23099);内蒙古自治区直属高校基本科研业务费项目(GXKY23Z008)