摘要
目的:利用网络药理学探索小陷胸汤治疗2型糖尿病(T2DM)的药理机制。方法:在中药系统药理学技术平台(TCMSP)网站检索小陷胸汤的主要活性成分、对应的作用靶点及靶标基因,通过人类基因数据库(Gene Cards)获得T2DM的相关靶标基因,将药物活性成分靶点与T2DM靶点相映射,获得交集靶点即为小陷胸汤作用于T2DM的预测靶点。利用Cytoscape 3. 7. 1软件构建药物活性成分-交集靶点网络模型,选出关键活性成分。利用STRING网站构建交集靶点蛋白相互作用网络(PPI),选出关键靶点基因。利用DAVID 6. 8在线工具对交集靶点进行基因本体(GO)分析和基于京都基因与基因组百科全书(KEGG)通路富集分析。结果:小陷胸汤作用于T2DM的活性成分有30个,相关靶点156个,关键有效成分14个,关键靶点基因18个。GO分析显示,小陷胸汤治疗T2DM潜在基因的生物功能主要涉及转录调控、氧化应激、蛋白结合和炎症反应等;KEGG通路富集显示小陷胸汤治疗T2DM影响的通路主要有缺诱导因子-1(HIF-1)信号通路,肿瘤坏死因子(TNF)信号通路,Toll样受体信号通路,甲状腺激素信号通路,磷脂酰肌醇氧3激酶/蛋白激酶B(PI3K/Akt)信号通路,乙肝,丙肝,酪氨酸激酶受体2(Erb B)信号通路,钙离子信号通路和核转录因子-κB(NF-кB)信号通路等。结论:小陷胸汤治疗T2DM机制可能是通过抑制炎症因子分泌,参与抗炎反应,降低氧化应激,升高细胞内钙离子浓度,阻断胰高血糖素信号通路,激活PI3K/Akt通路等来改善胰岛素抵抗,提高胰岛素敏感性,降低血糖。
Objective: To explore the pharmacological mechanism of Xiao Xianxiongtang in treating type 2 diabetes mellitus(T2 DM) by network pharmacology. Method: The main active ingredients,corresponding targets and target genes of Xiao Xianxiongtang were searched on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) website. Relevant target genes of T2 DM were obtained through Gene Cards. The targets of drug active ingredients were mapped to the targets of T2 DM,and the intersection targets were obtained as the predictive targets of Xiao Xianxiongtang on T2 DM. Cytoscape 3. 7. 1 software was used to construct the drug active ingredient-intersection target network model and select the key active ingredients. Interactive protein-protein interaction network(PPI) was constructed by STRING website,and key target genes were selected.Gene function analysis(GO) and enrichment analysis based on the Kyoto encyclopedia of genes and genomes(KEGG) pathway were performed on the intersecting targets using DAVID6. 8 online tool. Result: Xiao Xianxiongtang had 30 active ingredients,156 relevant targets,14 key active ingredients and 18 key target genes on T2 DM. GO analysis showed that the biological functions of Xiao Xianxiongtang in the treatment of potential genes of T2 DM mainly involved transcriptional regulation,oxidative stress,protein binding and inflammatory reaction.KEGG pathway enrichment showed that the main pathways of Xiao Xianxiongtang in the treatment of T2 DM were hypoxia inducible factor-1(HIF-1) signaling pathway,tumor necrosis factor(TNF) signaling pathway,Toll-like receptor signaling pathway and thyroid hormone signaling pathway,phosphatidylinositol 3 kinase/protein kinase B(PI3 K/Akt) signaling pathway,hepatitis B,hepatitis C,tyrosine kinase receptor2(ErbB) signaling pathway,calcium signaling pathway and nuclear factor-kappa B(NF-κB) signaling pathway. Conclusion: Xiao Xianxiongtang is a multi-component,multi-target and multi-pathway process in the treatment of T2 DM. It plays an important role in the treatment of T2 DM by regulating transcription, oxidative stress, protein binding and inflammatory reaction. Conclusion: The mechanism of Xiao Xianxiongtang in treating T2 DM may alleviate insulin resistance,increase insulin sensitivity and reduce blood sugar by inhibiting the secretion of inflammatory factors,participating in anti-inflammatory response, reducing oxidative stress, increasing intracellular calcium concentration,blocking glucagon signaling pathway and activating PI3 K/Akt pathway.
作者
施岚尔
聂课朝
张文婧
郑美思
刘闯
朱章志
SHI Lan-er;NIE Ke-chao;ZHANG Wen-jing;ZHENG Mei-si;LIU Chuang;ZHU Zhang-zhi(The First Clinical School of Guangzhou University of Chinese Medicine,Guangzhou 510405,China;The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2020年第4期198-206,共9页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金面上项目(8187141299)。
关键词
小陷胸汤
2型糖尿病
网络药理学
作用机制
Xiao Xianxiongtang
type 2 diabetes mellitus
network pharmacology
mechanism of action
