Investigation of the effect of curcumin on protein targets in NAFLD using bioinformatic analysis

Background: Non-alcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder. Defects in function/expression of genes/proteins are critical in initiation/progression of NAFLD. Natural products may modulate these genes/proteins. Curcumin improves steatosis, inflammation, and fibrosis progression. Here, bioinformatic tools, gene-drug and gene-disease databases were utilized to explore targets, interactions, and pathways through which curcumin could impact NAFLD.

Methods: Significant curcumin-protein interaction was identified (high-confidence:0.7) in the STITCH database. Identified proteins were investigated to determine association with NAFLD. gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were analyzed for significantly involved targets (p < 0.01). Specificity of obtained targets with NAFLD was estimated and investigated in Tissue/Cells-gene associations (PanglaoDB Augmented 2021, Mouse Gene Atlas) and Disease-gene association-based EnrichR algorithms (Jensen DISEASES, DisGeNET).

Results: Two collections were constructed: 227 protein-curcumin interactions and 95 NAFLD-associated genes. By Venn diagram, 14 significant targets were identified, and their biological pathways evaluated. Based on gene ontology, most targets involved stress and lipid metabolism. KEGG revealed chemical carcinogenesis, the AGE-RAGE signaling pathway in diabetic complications and NAFLD as the most common significant pathways. Specificity to diseases database (EnrichR algorithm) revealed specificity for steatosis/steatohepatitis.

Conclusion: Curcumin may improve, or inhibit, progression of NAFLD through activation/inhibition of NAFLD-related genes.