Four targets play a key role in the treatment of rheumatoid arthritis with hydroxychloroquine: smoothened homolog (SMO), sphingosine kinase (SPHK) 1, SPHK2 and gatty-acid amide hydrolase (FAAH).
The related 3316 proteins’ network which regulate ErbB, HIF-1, NF-κB, FoxO, chemokines, MAPK, PI3K/Akt pathways participate in the multi-targets mechanism of hydroxychloroquine.
Molecular docking analysis demonstrated that hydrogen bonding and π-π stacking are the main forms of chemical force of hydroxychloroquine and the targets.
This study was performed to investigate the multi-targets mechanism of hydroxychloroquine (HCQ) in the treatment of rheumatoid arthritis (RA).
The predicted targets of HCQ and the proteins related to RA were returned from databases. Followed by protein-protein interaction (PPI) network, the intersection of the two group of proteins was studied. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment was used to analyse these proteins in a macro perspective. Finally, the candidate targets were checked by molecular docking.
The results suggested that HCQ in the treatment of RA was mainly associated with 4 targets that are smoothened homolog (SMO), sphingosine kinase (SPHK) 1, SPHK2 and gatty-acid amide hydrolase (FAAH), with their related 3276 proteins’ network which regulate ErbB, HIF-1, NF-κB, FoxO, chemokines, MAPK, PI3K/Akt pathways and so forth. Biological process were mainly focused in the regulation of cell activation, myeloid leukocyte activation, regulated exocytosis and so forth. Molecular docking analysis showed that hydrogen bonding and π-π stacking were the main forms of chemical force.
Our research provides protein targets affected by HCQ in the treatment of RA. SMO, SPHK1, SPHK2 and FAAH involving 3276 proteins become the multi-targets mechanism of HCQ in the treatment of RA.El texto completo de este artículo está disponible en PDF.
Keywords : Hydroxychloroquine, Rheumatoid arthritis, Treatment, Multi-targets, Network pharmacology