火把花根片“异病同治”红斑狼疮和类风湿性关节炎的功效网络与机制探讨

Study on efficacy network and mechanism of Huobahuagen Tablets “treating different diseases with same method” for lupus erythematosus and rheumatoid arthritis

目的基于网络药理学研究方法,并结合中医理论探讨火把花根片(HuoBaHuaGen Tablet,HBHGT)"异病同治"红斑狼疮(LE)和类风湿性关节炎(RA)的共同作用机制。方法通过TCMSP、Chinese Herb Dictionary等数据库并结合文献,搜集并获取HBHGT中的化合物及其作用靶点。利用CTD、PubMed、Drugbank等数据库并结合文献搜集LE和RA的疾病相关靶点。通过Cytoscape软件构建"单味药-成分-靶点"网络和"药物-靶点-疾病"相互作用(PPI)网络,并对构建网络的基因功能和信号通路进行分析。运用Cytoscape软件中的Clue GO插件进行GO分析和Pathway分析。结果共收集到火把花根主要成分为表儿茶素、雷公藤甲素、雷公藤内酯酮,且获得其关键靶点138个。通过GO分析和Pathway分析发现HBHGT"异病同治"LE和RA涉及EGFR、CRK、LCK等17个共有靶点,其作用机制可能与磷蛋白结合、ERBB2信号通路、肽基酪氨酸自磷酸化等生物过程有关,并通过受体酪氨酸激酶信号通路、FGFR3信号通路、Fcε受体(FCERI)信号传导通路等实现。其中受体酪氨酸激酶通路为HBHGT"异病同治"最主要通路。结论从靶点和通路2个方面证实,HBHGT在治疗RA和LE存在着极大的相似性,其中EGFR、CBL、LCK等靶点和EGFR相关信号通路为HBHGT发挥"异病同治"作用的关键靶点和通路。

Objective Based on the network pharmacology research method, combined with the theory of traditional Chinese medicine, to explore the mechanism of the interaction of Huobahuagen Tablets(HBHGT) for treating different diseases with same method between the lupus erythematosus(LE) and rheumatoid arthritis(RA). Methods The components in HBHGT and their targets were collected by using TCMSP, Chinese Herb Dictionary, and other databases in combination with literature. Disease-related targets for lupus erythematosus and rheumatoid arthritis were collected using databases such as CTD, PubMed, and Drugbank in conjunction with literature. The herb-ingredient-target network and drug-target-disease interaction PPI network were constructed by Cytoscape software, and the gene function and signaling pathway of the constructed network were analyzed. ClueGO plugin in Cytoscape software was used for GO analysis and Pathway analysis. Results The main components of torch flower roots were epicatechin,triptolide and triptonide, and 138 key targets were obtained. Through GO analysis and Pathway analysis, it was found that HBHGT for treating different diseases with same method between the lupus erythematosus and rheumatoid arthritis involved 17 common targets such as EGFR, CRK, and LCK, and its mechanism may be related to biological processes such as phosphoprotein binding, ERBB2 signaling pathway, peptidyl tyrosine autophosphorylation, and receptor tyrosine kinase signaling pathway, FGFR3 signaling pathway, Fcε receptor(FCERI) signaling pathway and other pathways. Receptor tyrosine kinase signaling pathway was the main pathway of HBHGT for treating different diseases with same method. Conclusion This study confirmed from the two aspects of target and pathway that HBHGTs had great similarities in the treatment of RA and LE. Among them, EGFR, CBL, LCK, and other targets and EGFR-related signaling pathways were the key targets and pathways of HBHGT for "different diseases with the same treatment".