基于网络药理学探讨小柴胡汤治疗亚急性甲状腺炎的分子机制

Molecular mechanism of action of Xiaochaihu decoction in treatment of subacute thyroiditis: A study based on network pharmacology

目的:基于网络药理学研究小柴胡汤治疗亚急性甲状腺炎的分子机制。方法:通过TCMSP数据库获取柴胡、黄芩、半夏、生姜、人参、大枣、甘草的主要化学成分及靶点,根据ADME筛选其中活性成分,通过GeneCards、OMIM、DRUGBANK数据库获取亚急性甲状腺炎主要靶点,采用String平台进行蛋白质互相作用分析。应用CytoScape 3.7.1软件构建“小柴胡汤活性成分-亚急性甲状腺炎靶点-通路”网络,在Metascape平台进行基因本体论(GO)、京都基因与基因组百科全书(KEGG)通路富集分析。结果:小柴胡汤治疗亚急性甲状腺炎的有效活性成分为槲皮素、豆甾醇、β-谷甾醇、山柰酚等,核心靶点有前列腺素-内过氧化物合酶2(PTGS2)、热休克蛋白90Alpha Family A类成员1(HSP90AA1)、钙调蛋白(CALM1)、前列腺素-内过氧化物合酶1(PTGS1)、雄激素受体(AR)、雌激素受体-1(ESR1)、核受体辅激活蛋白2(NCOA2)、一氧化氮合酶诱导型(NOS2)、钠电压门控通道α亚基5(SCN5A)、过氧化物酶体增殖物激活受体-γ(PPARG)等。小柴胡汤治疗亚急性甲状腺炎的生物通路主要有单纯疱疹感染、NF-κB信号通路、细胞凋亡、白细胞跨内皮迁移的通路以及AMPK信号通路等。结论:本研究初步揭示了小柴胡汤通过多成分、多靶点、多通路治疗亚急性甲状腺炎的作用机制,为小柴胡汤的临床应用提供了现代医学依据。

Objective:To investigate the molecular mechanism of Xiaochaihu decoction in the treatment of subacute thyroiditis based on network pharmacology.Methods:TCMSP database was used to obtain the main chemical components and targets of Bupleurum chinense,Scutellaria baicalensis,Pinellia ternata,ginger,Panax ginseng,jujube,and Radix Glycyrrhizae,and active components were screened out based on ADME.GeneCards,OMIM,and DRUGBANK databases were used to obtain the main targets of subacute thyroiditis,and String platform was used to analyze protein-protein interaction.CytoScape 3.7.1 software was used to establish a“Xiaochaihu decoction active components-subacute thyroiditis targets-pathway”network,and gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed on Metascape platform.Results:The active components of Xiaochaihu decoction in the treatment of subacute thyroiditis included quercetin,stigmasterol,beta-sitosterol,and kaempferol,and the core targets included prostaglandin-endoperoxide synthase 2,heat shock protein 90kDa alpha class A member 1,calmodulin,prostaglandin-endoperoxide synthase 1,androgen receptor,estrogen receptor-1,nuclear receptor coactivator 2,inducible nitric oxide synthase 2,sodium voltage-gated channelαsubunit 5,and peroxisome proliferator-activated receptor-γ.The main biological pathways involved in the treatment of subacute thyroiditis by Xiaochaihu decoction included herpes simplex infection,the NF-κB signaling pathway,cell apoptosis,leukocyte transendothelial migration,and the AMPK signaling pathway.Conclusion:This study preliminarily reveals that Xiaochaihu decoction exerts a therapeutic effect on subacute thyroiditis through multiple components,targets,and pathways,which provides a modern medical basis for the clinical application of Xiaochaihu decoction.