六味调更汤治疗更年期Ⅱ型糖尿病的网络药理学机制研究

Effective Mechanism of Liuwei Tiaogeng Decoction on Climacteric Type 2 Diabetes Mellitus Based on Network Pharmacology

目的采用网络药理学的方法对六味调更汤治疗更年期Ⅱ型糖尿病的分子作用机制进行研究。方法利用中药系统药理学数据库与分析平台(TCMSP),收集六味调更汤的活性成分,搜寻潜在靶点,借助STRING平台构建蛋白互作网络(PPI),使用Cytoscape 3.6.0软件筛选出关键靶点。用DAVID平台对关键靶基因进行GO生物过程富集,分析靶点的KEGG信号通路及相关的疾病富集。利用NCBI平台查找疾病靶标,最后使用Cytoscape 3.6.0软件对成分靶标和疾病靶标进行网络拓扑学分析。结果研究得到齐敦果酸、beta-谷甾醇、檞皮素等206个主要活性成分,其中活性成分度值较高的为β-谷甾醇、山奈酚及槲皮素等39个关键靶标,其与733个更年期Ⅱ型糖尿病靶标交集后得23个交集靶标。通过基因功能富集平台DAVID分析信号通路,得到雌激素信号转导通路(Estrogen signaling pathway)、PI3K-Akt信号通路(PI3K-Akt signaling pathway)等关键通路。结论六味调更汤中的活性成分主要通过CASP8、ESR1、Akt1等靶标作用于PI3K-Akt信号通路和雌激素信号转导通路达到对更年期Ⅱ型糖尿病的治疗作用。

Objective The molecular mechanism of Liuwei Tiaogeng Decoction in the treatment of climacteric type 2 diabetes mellitus was studied by network pharmacology. Methods The active ingredients in Liuwei Tiaogeng Decoction were collected and potential targets were searched in TCMSP. Protein-protein interaction network(PPI)was constructed by STRING platform,and key targets were screened by Cytoscape 3.6.0 software. The key target genes were enriched by GO biological process using DAVID platform, and KEGG signaling pathway and related disease enrichment were analyzed. The NCBI platform was used to search disease targets. Finally,Cytoscape 3.6.0 software was used to analyze the network topology of component targets and disease targets. Results Two hundred and six main active components were obtained including oleanolic acid,β-sitosterol and quercetin;the ones with higher degree values are β-sitosterol, quercetin and kaempferol. There are 23 common targets between 39 key targets of the components and 733 key targets of climacteric type 2 diabetes mellitus. Estrogen signaling pathway,PI3 K-Akt signaling pathway and other key pathways were obtained after analysis by gene function enrichment platform DAVID. Conclusion The treatment of climacteric type 2 diabetes mellitus by Liuwei Tiaogeng decoction was achieved by CASP8, ESR1 and other targets through PI3 K-Akt signaling pathway and estrogen signaling pathway.