Xiao Lu, Lin Shudian, Zhan Feng
Department of Rheumatology and Immunology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Hainan, China.
Front Pharmacol. 2022 Sep 19;13:906763. doi: 10.3389/fphar.2022.906763. eCollection 2022.
We aimed to explore and verify the mechanism underlying the action of the active ingredients of (PRA) in the treatment of rheumatoid arthritis (RA). The protein targets of PRA's six active ingredients and RA were identified. Then, the intersection of the two groups was studied. The drug-target network was constructed, visualized, and analyzed by Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were performed to analyze these genes. Furthermore, we validated our predictions of the potential targets through a docking study. Finally, the anti-inflammatory effect of Palbinone (PB), one of the active ingredients of PRA, was tested by conducting and studies. Six active ingredients of PRA were identified, and 103 overlapping genes were discovered. Functional enrichment analysis indicated that the genes are mostly enriched in IL-17 signaling pathway, Th17 cell differentiation, and the FoxO, ErbB, and TNF signaling pathways. 10 hub genes and two gene cluster modules were identified by Cytoscape. Molecular docking analysis proved that PB was able to bind to the ATP binding site of Janus kinase (JAK)1, thereby acting as a potential inhibitor of JAK1. and studies demonstrated that PB exerts its anti-inflammatory role the inhibition of JAK1. We constructed a multitarget pharmacological network of PRA in RA treatment. PB, one of the active compounds of PRA, was demonstrated to be a promising inhibitor of JAK1.
我们旨在探索并验证（PRA）活性成分治疗类风湿关节炎（RA）的作用机制。确定了PRA六种活性成分和RA的蛋白质靶点。然后，研究了两组的交集。通过Cytoscape软件构建、可视化并分析了药物-靶点网络。进行了基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析以分析这些基因。此外，我们通过对接研究验证了对潜在靶点的预测。最后，通过进行……和……研究测试了PRA活性成分之一帕尔比诺酮（PB）的抗炎作用。确定了PRA的六种活性成分，发现了103个重叠基因。功能富集分析表明，这些基因主要富集于IL-17信号通路、Th17细胞分化以及FoxO、ErbB和TNF信号通路。通过Cytoscape确定了10个枢纽基因和两个基因簇模块。分子对接分析证明，PB能够与Janus激酶（JAK）1的ATP结合位点结合，从而作为JAK1的潜在抑制剂发挥作用。……和……研究表明，PB通过抑制JAK1发挥其抗炎作用。我们构建了PRA治疗RA的多靶点药理网络。PRA的活性化合物之一PB被证明是一种有前景的JAK1抑制剂。
