苓桂术甘汤改善胰岛素抵抗的网络药理学分析  

Network Pharmacology Analysis of Ling Gui Zhu Gan Decoction in Treatment of Insulin Resistance

作　　者：罗力[1] 刘春菇 黄钰[2] 张震宇[2] 余耀和 许帅[3] 龙舒妮 LUO Li;LIU Chungu;HUANG Yu;ZHANG Zhenyu;YU Yaohe;XU Shuai;LONG Shuni(Chinese Medicine Department of Guangzhou Xinhai Hospital,Guangzhou 510300 Guangdong,China;Endocrinology Department of Guangzhou Xinhai Hospital,Guangzhou 510300 Guangdong,China;Endocrinology Department of Shenzhen Baoan District Hospital of Traditional Chinese Medicine,Shenzhen 518101 Guangdong,China)

机构地区：[1]广州新海医院中医科,广东广州510300 [2]广州新海医院内分泌科,广东广州510300 [3]深圳市宝安区中医院内分泌科,广东深圳518101

出　　处：《中药新药与临床药理》2021年第11期1685-1691,共7页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：广东省中医药局科研项目(20212194)。

摘　　要：目的基于网络药理学探讨苓桂术甘汤改善胰岛素抵抗(IR)的分子机制。方法利用中药系统药理学分析平台(TCMSP)获取苓桂术甘汤的活性成分及作用靶点,通过OMIM、DisGenet、KEGG、TTD、GAD、Drugbank等数据库获取IR疾病相关靶点,并利用VennDiagram包获得二者的交集靶点即为苓桂术甘汤治疗IR的潜在作用靶点。利用Cystoscape 3.6.0软件及STRING数据库分别构建中药-活性成分-潜在作用靶点网络、苓桂术甘汤治疗IR潜在作用靶点的蛋白相互作用(PPI)网络,并进行网络特异性分析,最后借助topGO、GOplot包对结果进行可视化处理,阐明可能的关键靶点和关键通路。采用org.Hs.eg.db、ClusterPofiler包对苓桂术甘汤治疗IR的潜在作用靶点进行GO功能及KEGG通路富集分析。结果共筛选出苓桂术甘汤120个活性成分、73个潜在作用靶点。分析得到槲皮素、柚皮素、山柰酚、芒柄花素、β-谷甾醇等关键活性成分,维甲酸X受体α(RXRA)、雌激素α受体(ESR1)、丝氨酸/苏氨酸蛋白激酶1(AKT1)等关键靶点。苓桂术甘汤对IR的治疗作用与糖脂代谢、激素应答、转录过程和氧化应激等生物学过程相关,涉及晚期糖基化(AGERAGE)信号通路、肿瘤坏死因子(TNF)信号通路、磷脂酰肌醇-3激酶/蛋白激酶B(PI3K/AKT)信号通路等多条通路。结论苓桂术甘汤可能主要通过槲皮素、柚皮素、山柰酚等活性成分调节糖脂代谢、肿瘤坏死因子等信号通路发挥治疗IR的作用。Objective To explore the potential mechanism of Ling Gui Zhu Gan decoction in ameliorating insulin resistance using network pharmacology.Methods Firstly,the chemical compounds and potential targets of Ling Gui Zhu Gan decoction were collected from TCMSP database.Targets related to insulin resistance(IR)were obtained on OMIM,DisGenet,KEGG,TTD and GAD databases.Meanwhile,the Ling Gui Zhu Gan decoction-IR intersection targets were presented by Venn Diagram package.Then,the “herbs-active components-targets” network and the Ling Gui Zhu Gan decoction-IR interaction network were constructed by Cystospape 3.6.0.Moreover,network topological analysis of the both two networks were conducted to explore crucial nodes.Finally,GO analysis and KEGG enrichment analysis of the Ling Gui Zhu Gan decoction-IR interaction network were performed by the org.Hs.eg.db and the ClusterPofiler package.Results There were 120 active components and 73 potential targets in Ling Gui Zhu Gan decoction.Active components with high scores included quercetin,naringenin,kaempferol,formononetin,and β-sitosterol,etc.The key targets in Ling Gui Zhu Gan decoction-IR interaction network included RXRA,ESR1,AKT1,etc.GO analysis revealed that the biological progress involving Ling Gui Zhu Gan decoction may related to metabolic process of glucose and lipid,hormone response,transcription process and oxidative stress,etc.The KEGG pathways might be enriched in AGE-RAGE signaling pathway,TNF signaling pathway,PI3 K/AKT signaling pathway,and other pathways,etc.Conclusion Quercetin,naringenin,kaempferol,and other components in Ling Gui Zhu Gan decoction showed important implications in improving insulin resistance through regulating glucolipid metabolism pathway,TNF pathway,and other pathways.

关 键 词：苓桂术甘汤 胰岛素抵抗 网络药理学 糖脂代谢 肿瘤坏死因子 分子机制 信号通路 

分 类 号：R285.5[医药卫生—中药学] R857.3[医药卫生—中医学]