基于网络药理学和分子对接探讨漆赛尔桑当松汤治疗类风湿性关节炎的作用机制

Study on the mechanism of Qi-Sai-Er-Sang-Dang-Song Decoction in treating rheumatoid arthritis based on network pharmacology and molecular docking

目的:基于网络药理学与分子对接探讨藏药漆赛尔桑当松汤治疗类风湿性关节炎的抗炎机制。方法:通过前期研究结果并将结果导入PubChem数据库和Swiss-Target-Prediction数据库收集漆赛尔桑当松汤药物的活性成分和作用靶点。通过Gene Cards等疾病数据库获取类风湿性关节炎的相关基因,将两者放入Venny中提取交集并导入STRING数据库构建PPI网络。使用Metascape数据库进行GO富集分析和KEGG通路分析。最后,将核心靶点与活性化合物进行分子对接。结果:筛选出74个漆赛尔桑当松汤的有效化学成分,检索出769个基因靶点,疾病数据库得到疾病靶点302个,两者取交集后共得到59个共同靶点。PPI网络显示类风湿性关节炎可能与TNF、VEGFA、CXCL8、TLR4等核心基因相关。GO和KEGG分析显示,漆赛尔桑当松汤治疗类风湿性关节炎主要涉及细胞因子产生的正向调节和细胞迁移的正向调节。信号通路主要包括MAPK、PI3K-Akt和C型凝集素受体信号通路。分子对接结果显示Abelmanihotols B、Abelmanihotols C和Rhamnocitrin与TLR4和NOTCH3靶点具有较高的亲和力。结论:漆赛尔桑当松汤能缓解类风湿性关节炎引起的关节炎症,其中MAPK、PI3K-Akt、NOTCH信号通路可能是漆赛尔桑当松汤治疗类风湿性关节炎的潜在作用机制。

Objective:To study the anti-inflammatory mechanism of Tibetan medicine Qi-Sai-Er-Sang-Dang-Song Decoction in treating rheumatoid arthritis(RA)based on the network pharmacology and molecular docking.Method:The active components and targets of the drugs in Qi-Sai-Er-Sang-Dang-Song Decoction were collected through previous research results and importing the results into the PubChem and Swiss-Target-Prediction databases.RA-related genes were obtained by disease databases such as Gene Cards.They were put into Venny to obtain the intersection which was imported into the STRING database to construct the PPI network.The Matescape database was used for GO enrichment analysis and KEGG pathway analysis.Finally,molecular docking of the core targets with the active compounds was performed.Result:74 effective components in Qi-Sai-Er-Sang-Dang-Song Decoction were screened.769 gene targets were retrieved,302 disease targets were obtained by the disease databases,and 59 common targets were obtained by taking their intersection.The PPI network showed that RA was likely related to the core genes including TNF,VEGFA,CXCL8,TLR4,etc.GO and KEGG analysis revealed that the treatment of RA by Qi-Sai-Er-Sang-Dang-Song Decoction mainly involved the positive regulation of cytokine production and cell migration.The signaling pathways primarily included MAPK,PI3K-Akt and C-type lectin receptor signaling pathways.The molecular docking results showed that Abelmanihotols B,Abelmanihotols C and Rhamnocitrin had high affinity with the targets TLR4 and NOTCH3.Conclusion:Qi-Sai-Er-Sang-Dang-Song Decoction can alleviate RA-caused joint inflammation.MAPK,PI3K-Akt and NOTCH signaling pathways may be the potential mechanism that Qi-Sai-Er-Sang-Dang-Song Decoction in treating RA.