网络药理学技术预测延胡索抗糖尿病作用及初步验证研究

Predication of Anti-Diabetes Effects of Corydalis yanhusuo Alkaloids with Pharmacological Network Technology and Experimental Validation in ICR Mice

目的利用网络药理学技术预测延胡索生物碱的抗糖尿病作用并加以验证。方法全面收集Pubmed、CNKI、万方和维普数据库中与延胡索的生物碱成分相关的靶点信息。在OMIM数据库检索糖尿病相关疾病的靶点,通过共享靶点实现与生物碱成分的关联,构建并分析延胡索生物碱"成分-靶点-糖尿病"网络。采用胰岛素抵抗模型和糖尿病模型验证预测结果。结果延胡索生物碱的"成分-靶点"网络中,延胡索各成分的靶点涉及神经递质及其代谢酶、离子通道、信号蛋白和酪氨酸激酶样受体和G蛋白偶联受体。延胡索"成分-靶点"网络和"糖尿病相关疾病-靶点"网络共享多个靶点,其中涉及多种重要枢纽节点,如NOS3、VEGF等,多种成分的靶点与2型糖尿病、高血压、肥胖、胰岛素抵抗等疾病关联,提示延胡索生物碱可能具有抗糖尿病相关疾病作用。延胡索醇提物明显降低对正常和糖尿病小鼠血糖、高脂诱导胰岛素抵抗小鼠糖耐量,这些结果与网络药理学预测结果较为一致。结论延胡索生物碱有潜在抗糖尿病、糖尿病并发症的作用。

OBJECTIVE To predict the anti-diabetes effects of Corydalis yanhusuo alkaloids with pharmacological network technology and verify the results in animal models. METHODS Targets of Corydalis yanhusuo alkaloids were collected from Pubmed, CNKI, Wangfang and VIP databases, and targets for treatment of diabetes and diabetic complications were searched from OMIM database. The ＂components-targets-diabetes＂ network was constructed and analyzed with cytoscape 2. 8.2. Diabetes model was established by STZ injection. RESULTS The targets of Corydalis yanhusuo alkaloids covered many kinds of protein, including ion channel, G coupled protein, and signal proteins such as potassium channel, MAPK/ERK, VEGF and NOS3. In the network, Corydalis yanhusuo alkaloids associated with diabetes and diabetic complications, especially, non-insulin dependent diabetes, obesity, and diabetic complications via modulation of NOS3, VEGF, INSR, KCNJ11 and IRS1, indicating potential effects of Corydalis yanhusuo for diabetes and diabetic complications. Corydalis yanhusuo alkaloids decreased blood glucose in normal and diabetic ICR mice and improved sugar tolerance in insulin-resistant mice, which was in conformity with the prediction. CONCLUSION Corydalis yanhusuo alkaloids show potential effects on diabetes and diabetic complications.