[关键词]
[摘要]
目的:利用网络药理学、分子对接和体外实验研究黎药胆木有效成分治疗糖尿病肾病的关键作用靶点和潜在作用机制。 方法:通过CNKI、PubMed、SwissTargetPrediction数据库检索胆木活性成分作用靶点,同时在GeneCards、Disgenet数据库获取糖尿病肾病靶点,取交集后导入String数据库筛选核心靶点,对靶点进行富集分析以及分子对接验证,细胞实验验证胆木中有效成分对糖尿病肾病的保护作用。 结果:筛选得到9种有效成分,258个对应靶点5 333个疾病靶点,取交集得132个共同靶点,主要为IL6、ALB、STAT3、PPARG、EGFR等靶点;经富集分析可知胆木治疗糖尿病肾病信号通路主要涉及基因表达的正调控、细胞溶质、ATP结合、HIF‑1、FoxO、PI3K‑Akt等通路;分子对接可知胆木活性成分与核心蛋白之间能自发结合,同时将结合分数及靶点通路相关度最高的胆木化学成分常春藤皂苷元进行体外实验验证,结果表明常春藤皂苷元能够保护高糖诱导的细胞凋亡,抑制细胞迁移并提高细胞增值率。 结论:本研究通过网络药理学及分子对接研究胆木治疗糖尿病肾病的作用成分及机制,发现胆木可通过多靶点、多成分、多通路发挥治疗作用。体外实验初步验证了胆木中活性成分常春藤皂苷元可缓解高糖诱导的细胞损伤,提高肾足细胞增值率,表明胆木中常春藤皂苷元可能是治疗糖尿病肾病的基础所在,为研究黎药胆木应用提供了新思路。
[Key word]
[Abstract]
Objective:To study the potential mechanism of the active ingredients of Liyao Nauclea(N.) officinalis in the treatment of diabetic nephropathy by using network pharmacology and in vitro experiments. Methods:Through CNKI, PubMed, and SwissTargetPrediction databases, the active ingredients and targets of N. officinalis were searched. At the same time, the targets of diabetic nephropathy were obtained in GeneCards and Disgenet databases. After the intersection was imported into the String database, the core targets were screened, and the targets were enriched and analyzed. Molecular docking verification, and cell experiments verified the effective protective effect of N. officinalis on diabetic nephropathy. Results:A total of 9 effective components, 258 corresponding targets and 5 333 disease targets were screened, and 132 common targets were obtained by intersection, mainly IL6, ALB, STAT3, PPARG, EGFR and other targets. Enrichment analysis showed that the signaling pathways of N. officinalis in the treatment of diabetic nephropathy mainly involved positive regulation of gene expression, cell solute, ATP binding, HIF‑1, FoxO, PI3K‑Akt and other pathways. Molecular docking showed that the active components of N. officinalis could spontaneously bind to the core protein. At the same time, the Hederagenin with the highest binding fraction was verified in vitro. The results showed that Hederagenin could protect high glucose‑induced apoptosis, inhibit cell migration and increase cell proliferation rate. Conclusion:In this study, the components and mechanisms of N. officinalis in the treatment of diabetic nephropathy were studied by network pharmacology, and it was found that N. officinalis could play a therapeutic role through multi‑target, multi‑component and multi‑pathway. Hederagenin contained in N. officinalis is likely to be the basis for its treatment of diabetic nephropathy. In vitro experiments have preliminarily verified that the active ingredient hederagenin in N. officinalis can alleviate cell damage induced by high glucose and increase cell proliferation rate, which provides a new idea for the treatment of diabetic nephropathy by Li medicine N. officinalis.
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[基金项目]
海南省自然科学基金(823MS147);海南省自然科学基金高层次人才项目(820RC624)