基于网络药理学研究白仙风汤剂治疗类风湿性关节炎的药理机制

Pharmacological mechanism of Chinese herbal compound Bai Xian Feng Decoction in treating rheumatoid arthritis based on network pharmacology

目的基于网络药理学探讨白仙风汤剂治疗类风湿性关节炎的活性成分,并预测其可能机制。方法白仙风汤剂中白芍、甘草、青风藤、威灵仙4味草药在TCMSP数据库中检索,经口服吸收率(OB)、类药性、半衰期条件筛选得到药物有效成分,并进行靶点预测;从OMIM、TTD、PharmGKB和GAD数据库对类风湿性关节炎靶点进行检索;使用Cytoscape 3.2.1软件构建药物成分靶点蛋白相互作用网络,对该网络进行拓扑学分析得到核心化学成分及核心靶点;对核心靶点基因进行GO通路分析和KEGG生物过程分析。结果筛选得到白芍有效成分10个,甘草有效成分66个,青风藤有效成分6个,威灵仙有效成分8个,删除共有的有效成分,共有83个有效活性化合物,对这些化合物进行靶点预测,共得到260个药物靶点;对疾病相关靶点进行检索,共得到58个疾病靶点。通过对药物成分-疾病靶点网络节点的拓扑学分析得到槲皮素、β-谷甾醇、豆甾醇、甘草素等19个核心化学成分,及丝裂原活化蛋白激酶14、雌激素受体、糖皮质激素受体等9个核心靶点,对这些靶点进行通路富集发现药物治疗疾病涉及血管内皮生长因子(VEGF)信号通路、调节脂肪细胞中的脂肪分解、催乳素信号通路、雌激素信号通路、TNF信号通路等11条通路。结论白仙风汤剂主要通过VEGF信号通路、调节脂肪细胞中的脂肪分解、催乳素信号通路等多条途径实现类风湿性关节炎的治疗作用,表现出多成分、多靶点、多通路的特点,与类风湿关节炎治疗机制相一致。

Objective Based on network pharmacology,the basis of active ingredients of rheumatoid arthritis treated by Bai Xian Feng decoction was discussed,and its possible mechanism was predicted.Method The four herbs in Baixianfeng Decoction,Paeonia lactiflora,Licorice,Sinomenia sinensis and Willingxian,were searched in TCMSP database.The active ingredients were screened by oral absorption rate(OB),medicinal properties and half-life conditions,and the target was predicted.The target of rheumatoid arthritis was searched from OMIM,TTD,PharmGKB and GAD databases.The target eggs of drug components were constructed by Cytose 3.2.1 software.White Interaction Network(BIN)is used to obtain core chemical components and core targets by topological analysis,GO pathway analysis and KEGG biological process analysis of core target genes.Result There were 10 effective ingredients of Paeoniae Radix Alba,64 effective components of licorice,6 effective constituents of Caulis Sinomenii and 8 effective components of Radix Clematidis.A total of 83 effective active compounds were deleted.The targets of these compounds were predicted,and 260 drug targets were obtained.At the same time,a total of 58 disease targets were obtained.By the topology analysis of the network nodes,19 core chemical components,such as beta sterol,sterol,glycyrrhizin and naringin,are obtained,and9 cores,such as mitogen activated protein kinase 14,estrogen receptor,glucocorticoid receptor,etc.Targeting,the pathway enrichment of these targets is found to involve 11 pathways,such as VEGF signaling pathway,estrogen signaling pathway,TNF signaling pathway,and cGMP-PKG signaling pathway.Conclusion Baixianfeng Decoction mainly regulates the treatment of rheumatoid arthritis through VEGF signaling pathway,regulating fat breakdown in fat cells and prolactin signaling pathway.Baixianfeng Decoction for rheumatoid arthritis shows multi-component,multi-target,multi-channel characteristics,consistent with the treatment mechanism of rheumatoid arthritis.