基于网络药理学探讨黄柏-透骨草治疗类风湿关节炎的机制

Mechanisms of Cortex phellodendri-Herba tuberculate speranskia in treatment of rheumatoid arthritis based on network pharmacology

目的采用网络药理学研究方法筛选黄柏-透骨草治疗类风湿关节炎(RA)的活性成分、作用靶点及通路,探讨其潜在作用机制。方法采用中药系统药理学分析平台(TCMSP)筛选黄柏-透骨草中口服生物利用度≥30%,类药性≥0.18,渗透性≥0.4的活性化合物。通过DisGeNET数据库筛选RA相关的疾病靶点,应用Cytoscape 3.7.1软件构建黄柏-透骨草治疗RA的成分-靶点-通路网络,采用String数据库构建蛋白质相互作用网络,利用DAVID数据库对靶点进行基因本体(GO)和基因功能(KEGG)富集分析。结果筛选出防己碱、小檗碱、槲皮素等10个药物核心成分,前列腺素G/H合成酶2、磷酸肌激酶、丝裂原活化蛋白激酶等13个关键靶点,共同靶点主要富集于正向调控蛋白磷酸化、肿瘤坏死因子(TNF)通路、Toll样受体通路、血管内皮生长因子(VEGF)通路、缺氧诱导因子-1(HIF-1)通路、PI3K/AKT信号通路等132个生物过程和89条信号通路。结论黄柏-透骨草对治疗RA具有多成分-多靶点-多途径的作用特点,作用机制可能与调节免疫细胞和滑膜成纤维细胞的异常增殖、降低炎症反应有关。

AIM To screen the active components,targets and pathways of Cortex phellodendri(CP)-Herba tuberculate speranskia(HTS)in the treatment of rheumatoid arthritis(RA)and explore its potential mechanism.METHODS Traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP)was used to screen the bioactive compounds with oral bioavailability(OB)≥30%,drug-likeness(DL)≥0.18,Caco-2 permeability≥0.4.The disease targets related to RA were screened by the DisGeNET database,and the component-target-pathway network of CP-HTS in the treatment of RA was constructed by using the software of Cytoscape 3.7.1.The protein-protein interaction network was constructed by using String database,and the target was enriched by using DAVID to analyze gene ontology(GO)and gene function(KEGG).RESULTS Ten core components,such as palmatine,berberine and quercetin were screened out.And 13 key targets,such as PTGS2,PI3 K and MAPK were identified.The common targets were mainly involved in 132 biological process and 89 signaling pathways,such as regulation of protein phosphorylation,tumor necrosis factor(TNF)pathway,toll-like receptor pathway,vascular endothelial growth factors(VEGF)pathway,hypoxia-inducible factor-1(HIF-1)pathway and PI3 K/AKT signaling pathway.CONCLUSION The anti-RA effects of CP-HTS is based on the multi-component,multi-target and multi-pathway.The mechanism may be related to regulating the abnormal proliferation of immune cells and synovial fibroblasts and reducing the inflammatory response.