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Investigation of the Effect of Curcumin on Protein Targets in NAFLD Using Bioinformatic Analysis
Ali Mahmoudi1, Alexandra E Butler2, Muhammed Majeed3
1Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad 9177899191, Iran.
Abstract:
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.
Insights
Curcumin may impact non-alcoholic fatty liver disease (NAFLD) progression by modulating key genes and pathways. This study used bioinformatics to identify 14 significant targets linking curcumin to NAFLD, suggesting therapeutic potential.
Area of Science:
- Bioinformatics
- Molecular Biology
- Pharmacology
Background:
- Non-alcoholic fatty liver disease (NAFLD) is a widespread metabolic disorder.
- Gene and protein dysregulation is central to NAFLD development and progression.
- Natural compounds like curcumin show promise in managing NAFLD.
Purpose of the Study:
- To explore the molecular targets, interactions, and pathways affected by curcumin in NAFLD using bioinformatics.
- To identify specific genes and biological processes through which curcumin may influence NAFLD.
Main Methods:
- Utilized STITCH database for high-confidence curcumin-protein interactions.
- Analyzed Gene Ontology (GO) and KEGG pathways for identified targets.
- Assessed NAFLD specificity using PanglaoDB, Mouse Gene Atlas, and EnrichR algorithms (DisGeNET, Jensen DISEASES).
Main Results:
- Identified 14 significant targets connecting curcumin to NAFLD from 227 protein-curcumin interactions and 95 NAFLD genes.
- GO analysis indicated targets involved in stress and lipid metabolism.
- KEGG pathway analysis highlighted chemical carcinogenesis and AGE-RAGE signaling in diabetic complications and NAFLD.
Conclusions:
- Curcumin demonstrates potential in modulating NAFLD progression.
- Therapeutic effects may be achieved through the activation or inhibition of specific NAFLD-related genes.
- Identified pathways suggest mechanisms involving stress, lipid metabolism, and AGE-RAGE signaling.
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