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Article Publish Status: FREE
Abstract Title:

One of the active ingredients infunctions as JAK1 inhibitor in rheumatoid arthritis.

Abstract Source:

Front Pharmacol. 2022 ;13:906763. Epub 2022 Sep 19. PMID: 36199685

Abstract Author(s):

Lu Xiao, Shudian Lin, Feng Zhan

Article Affiliation:

Lu Xiao

Abstract:

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 conductingandstudies.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.andstudies demonstrated that PB exerts its anti-inflammatory rolethe 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.

Study Type : Animal Study, In Vitro Study

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