基于网络药理学的柴胡治疗癫痫有效活性成分、作用靶基因筛选及靶基因生物学功能分析

Screening of active components and action target genes of Chaihu(Bupleurum chinense)in treatment of epilepsy based on network pharmacology and biological function analysis of target genes

目的基于网络药理学筛选柴胡治疗癫痫的有效活性成分、作用靶基因,并分析其靶基因生物学功能。方法通过中药系统药理学技术平台(TCMSP)和SwissTargetPrediction数据库,筛选出柴胡的有效活性成分及其相关靶基因。利用GeneCards、TTD、DisGeNET、OMIM数据库检索出癫痫相关靶基因。利用Draw Venn Diagram在线工具将柴胡的有效活性成分靶基因与癫痫相关靶基因取交集,得到柴胡-癫痫的共同靶基因。利用R软件对柴胡-癫痫共同靶基因进行GO分子功能和KEGG信号通路富集分析。通过STRING数据库构建柴胡-癫痫共同靶基因的PPI网络图,根据度值筛选核心基因。根据柴胡-癫痫共同靶基因的“活性成分-靶点-通路”及PPI网络中的共同核心靶基因,选取受体、配体,利用Autodock4软件进行分子对接,验证柴胡-癫痫共同核心靶基因与柴胡有效活性成分的结合活性。结果得到柴胡有效活性成分14个及其靶基因273个,癫痫相关靶基因2020个,取交后集得到柴胡-癫痫共同靶基因77个。构建的柴胡-癫痫的“药物-活性成分-疾病-靶点”网络显示,柴胡通过槲皮素、豆甾醇、山奈酚等13种有效活性成分作用于ESR1、VEGFA等77个共同靶基因。柴胡-癫痫共同靶基因的GO分子功能主要涉及神经递质受体活性、细胞因子活性等,KEGG信号通路主要富集在IL-17信号通路、肿瘤坏死因子信号通路等。TP53、IL-1B、CXCL8、TNF等靶基因与豆甾醇、3,5,6,7-四甲氧基-2-(3,4,5-三甲氧基苯基)色酮等柴胡有效活性成分具有良好亲和力。结论槲皮素、豆甾醇、山奈酚等13种柴胡有效活性成分作用于ESR1、VEGFA等77个柴胡-癫痫共同靶基因,通过调节神经递质、抗炎、抗氧化应激等途径发挥治疗癫痫的作用。

Objective To screen out the active components and target genes of Chaihu(Bupleurum chinense) in the treatment of epilepsy based on network pharmacology,and to analyze the biological function of the target genes.Methods The active components and target genes of Bupleurum chinense were screened by TCMSP and Swiss Target Prediction database.GeneCards,OMIM,DisGeNET and TTD databases were used to collect the epilepsy-related genes.The common target genes of Bupleurum chinense and epilepsy were obtained by the intersection of the target genes of Bupleurum chinense and epilepsy with the online tool Draw Venn Diagram.R software was used to analyze the Gene ontology(GO) molecular function and Kyoto encyclopedia of genes and genomes(KEGG) signaling pathway enrichment of the common targets.STRING database was used for the protein-protein interaction(PPI) network analysis,and the core genes were screened according to the degree value.The common core target genes between the "active components-target genespathway" and the PPI network were selected as the receptors,and the molecular docking was conducted by using Autodock4 software to verify the binding activity.Results The results showed that 14 active components and 273 target genes of Bupleurum chinense and 2 020 epilepsy-related target genes were obtained.The "drug-active ingredient-diseasetarget genes" network showed that Bupleurum chinense acted on 77 common target genes such as ESR1 and VEGFA through 13 effective active ingredients such as quercetin,stigmasterol and kaempferol.Go molecular function of common target genes of Bupleurum chinense and epilepsy mainly involved neurotransmitter receptor activity and cytokine activity.KEGG signal pathway was mainly enriched in IL-17 signal pathway and tumor necrosis factor signal pathway,etc.The molecular docking-based virtual screening showed that the target genes of TP53,IL-1 B,CXCL8 and TNF,etc.had binding affinity with stigmasterol and 3,5,6,7-tetramethoxy-2-(3,4,5-trimethoxyphenyl) chromone.Conclusion Thirteen active components of Bupleurum chinense such as quercetin,stigmasterol and kaempferol,acting on 77 target genes like ESR1 and VEGFA,play a role in the treatment of epilepsy by regulating neurotransmitters,anti-inflammatory and antioxidant stress.