The protective effects of curcumin on depression: Genes, transcription factors, and microRNAs involved

We aim to identify the molecular mechanisms for curcumin's anti-depressant properties, including genes, transcription factors, and miRNAs. The Comparative Toxicogenomics Database, GeneMania, Metascape, MIENTURNET, and Cytoscape software were used as important data approaches in this study. Curcumin may have an anti-depressant effect via the relevant genes: ADORA2A, ALB, BDNF, FGF2, GLO1, GSK3B, IL6, MIF, NOS1, PTGS2, RELN, SELP, SOD1, and NR3C1. Co-expression (50.7 %) and physical interactions (28.7 %) were the primary relationships discovered by gene network analysis. The key pathways involved in curcumin's protective function against depression were “spinal cord injury”, “regulation of apoptotic signaling pathway”, “positive regulation of protein phosphorylation”, “folate metabolism”, “neuroinflammation and glutamatergic signaling”, and “inflammation response”. We also observed 74 miRNAs associated with depression that are targeted by curcumin, with hsa-miR-146a-5p having the greatest expression and interaction. PLSCR1, SNAI1, ZNF267, ATF3, and GTF2B were the most important transcription factors that regulated four curcumin-targeted genes. Curcumin's physicochemical characteristics and pharmacokinetics are consistent with its antidepressant effects due to its high gastrointestinal absorption, which did not remove it from the CNS, and its ability to penetrate the blood-brain barrier. Curcumin also inhibits CYP1A9 and CYP3A4. A toxicogenomic design in silico was applied. Our findings suggest that therapy optimization and further research into curcumin's pharmacological properties are required before it may be utilized to treat depression.