Jiang Yunbin, Zhong Mei, Long Fei, Yang Rongping
College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing 400715, China.
College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
Evid Based Complement Alternat Med. 2020 Jan 13;2020:2361865. doi: 10.1155/2020/2361865. eCollection 2020.
(Levl.) Hutch (THH) shows well clinical effect on rheumatoid arthritis (RA), but the active ingredients and molecular mechanisms remain unclear. This work was designed to explore these issues by network pharmacology. Compounds from THH were gathered by retrieving literatures. Compound-related and RA-related genes were identified using databases, and the overlapping genes were identified by Venn diagram. The active ingredients and genes of THH against RA were confirmed by dissecting interactions between overlapping genes and compounds using Cytoscape. SystemsDock website was used to further verify the combining degree of key genes with active ingredients. Pathway enrichment analysis was performed to decipher the mechanisms of THH against RA by Database for Annotation, Visualization and Integrated Discovery. A total of 123 compounds were collected, and 110 compounds-related and 1871 RA-related genes were identified, including 64 overlapping genes. The target genes and active ingredients of THH against RA comprised 64 genes and 17 compounds, the focus of which was PTGS2, triptolide, and celastrol. SystemsDock website indicated that the combing degree of PTGS2 with triptolide or celastrol was very good. The mechanisms of THH against RA were linked to 31 signaling pathways, and the key mechanism was related to inhibition of inflammation response through inactivating TNF and NF-kappa B signaling pathways. This work firstly explored the active ingredients and mechanisms of THH against RA by network pharmacology and provided evidence to support clinical effects of THH on RA.
（雷公藤）哈钦森（THH）对类风湿关节炎（RA）显示出良好的临床效果，但其活性成分和分子机制仍不清楚。这项工作旨在通过网络药理学探索这些问题。通过检索文献收集来自THH的化合物。使用数据库鉴定与化合物相关和与RA相关的基因，并通过维恩图鉴定重叠基因。使用Cytoscape剖析重叠基因与化合物之间的相互作用，从而确认THH抗RA的活性成分和基因。使用SystemsDock网站进一步验证关键基因与活性成分的结合程度。通过注释、可视化和综合发现数据库进行通路富集分析，以解读THH抗RA的机制。共收集到123种化合物，鉴定出110种与化合物相关的基因和1871种与RA相关的基因，其中包括64个重叠基因。THH抗RA的靶基因和活性成分包括64个基因和17种化合物，其中重点是PTGS2、雷公藤内酯醇和雷公藤红素。SystemsDock网站表明PTGS2与雷公藤内酯醇或雷公藤红素的结合程度非常好。THH抗RA的机制与31条信号通路相关，关键机制与通过使TNF和NF-κB信号通路失活来抑制炎症反应有关。这项工作首次通过网络药理学探索了THH抗RA的活性成分和机制，并为THH对RA的临床效果提供了支持证据。
