Curcumin’s molecular mechanism of action and targets in the treatment of rheumatoid arthritis: A network analysis and molecular docking study

Abstract

Abstract Introduction: Rheumatoid Arthritis (RA) is an autoimmune disorder that majorly affects the joints leading to pain, swelling, and stiffness and inflammation. Curcumin is a chemical compound from Curcuma longa(Tumeric). The aim of this study was to investigate the molecular mechanisms underlying the treatment of RA using curcumin. Methods: Curcumin associated targets were retrieved from SwissTargetPrediction, PharmMapper and DrugBank. The RA associated targets were retrieved from OMIM, GeneCards, NCBI gene databases. GeneVenn was used to determine overlapping genes (RA-curcumin associated targets). The targets were used to construct a compound-disease target network. Gene Ontology enrichment analysis was done to identify the molecular function, cellular components and biological processes associated with the targets. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses was performed to identify top pathways with p< 0.05. A disease target-pathway network (D-P) was constructed and then merged with the C-D network to produce a compound-disease target-pathway network (C-D-P). Results: We obtained 190 RA-curcumin associated targets.Gene ontology analysis revealed response to peptide, protein kinase complex and non-membrane spanning protein kinase activity as the major biological processes, cellular componentsand molecular functionterms respectively. Network analysis revealed SRC, AKT1 and AKT2 as the hub targets. Molecular docking showed that curcumin can bind stably to the hub targets. Conclusion: Curcumin can interact with various proteins involved in the treatment of RA which can guide further its clinical application.