基于网络药理学探讨桃核承气汤治疗血瘀型慢性前列腺炎/慢性盆腔疼痛综合征的机制

Discussion on the mechanism of Taohe Chengqi Decoction in the treatment of the blood stasis type of chronic prostatitis/chronic pelvic pain syndrome based on network pharmacology

目的基于网络药理学探讨桃核承气汤治疗血瘀型慢性前列腺炎(CP)/慢性盆腔疼痛综合征(CPPS)的潜在作用机制。方法筛选桃核承气汤的有效成分及CP/CPPS相关靶点基因,构建蛋白相互作用(PPI)网络,进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,对关键成分和靶点进行分子对接。结果桃核承气汤的潜在活性成分共有140个,CP/CPPS的差异基因1256个,共同靶点61个。桃核承气汤治疗CP/CPPS的关键蛋白包括蛋白激酶B(Akt1)、白介素(IL)-6、血管内皮生长因子A(VEGFA)、表皮生长因子(EGF)、肿瘤坏死因子(TNF)等,主要有效成分为槲皮素、β-谷甾醇和山柰酚等。GO功能富集分析显示,桃核承气汤主要通过调控RNA聚合酶Ⅱ启动子转录、细胞凋亡、丝裂原活化蛋白激酶(MAPK)活性、环磷酸腺苷、炎症反应和细胞因子活性等治疗CP/CPPS。KEGG通路富集分析显示,桃核承气汤可通过晚期糖基化终末产物-受体、MAPK、磷脂酰肌醇-3-激酶(PI3K)-Akt、TNF、Janus激酶-信号转导和转录激活因子(JAK-STAT)信号通路等对CP/CPPS起到治疗作用。分子对接结果表明主要活性成分与关键靶点结合性较好。结论桃核承气汤治疗CP/CPPS具有多靶点、多途径的特点。

Objective To investigate the potential mechanism of Taohe Chengqi Decoction in the treatment of the blood stasis type of chronic prostatitis(CP)/chronic pelvic pain syndrome(CPPS)by network pharmacology.Methods The active components of Taohe Chengqi Decoction and the related target genes of CP/CPPS were screened to construct the protein-protein interaction(PPI)network.Gene ontology(GO)function enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were carried out.The molecular docking of the key components and targets was conducted.Results There were 140 potential active components of Taohe Chengqi Decoction,1256 differential genes of CP/CPPS,and 61 common targets.The key proteins of Taohe Chengqi Decoction for the treatment of CP/CPPS include protein kinase B(Akt1),interleukin(IL)-6,vascular endothelial growth factor A(VEGFA),epidermal growth factor(EGF),tumor necrosis factor(TNF),etc.,and the main effective components include quercetin,β-sitosterol and kaempferol,etc.GO function enrichment analysis showed that Taohe Chengqi Decoction mainly achieved the therapeutic effect on CP/CPPS by regulating RNA polymeraseⅡpromoter transcription,cell apoptosis,mitogen-activated protein kinase(MAPK)kinase activity,cyclic adenosine monophosphate,inflammatory response and cytokine activity,etc.KEGG pathway enrichment analysis showed that Taohe Chengqi Decoction can treat CP/CPPS through advanced glycation end products-receptor signaling pathway,MAPK signaling pathway,phosphatidylinositol-3-kinase(PI3 K)-Akt signaling pathway,TNF,Janus kinase-signal transducer and activator of transcription(JAK-STAT)signaling pathway,and other signaling pathways.Molecular docking results showed that the main active ingredients have better binding to the key targets.Conclusions Taohe Chengqi Decoction has the characteristics of multi-target and multi-pathway in the treatment of CP/CPPS.