Roles of Curcumin on Cognitive Impairment Induced by a Mixture of Heavy Metals.

We aimed to explore the molecular mechanisms of curcumin's protective action against heavy metal-related cognitive impairment (CI). In silico analysis, CTD, SwissADME, AutoDock Vina, Metascape, GeneMania, and MIENTURNET were key approaches. The server-predicted interactions (41.7%) and physical interactions (35.7%) were found to be the most important interactions in the gene network analysis. The most important pathways involved in curcumin's protective activity against heavy metals were categorized as "regulation of neuron apoptotic process" and "negative regulation of apoptotic signaling route". These pathways were also emphasized in the protein-protein interaction enrichment analysis. Curcumin was also well-positioned inside the CASP3 binding region. Three key miRNAs linked to CI, mixed heavy metals, and curcumin (hsa-miR-34a-5p, hsa-miR-24-3p, and hsa-miR-128-3p) were observed. These miRNAs were found to be related to the important pathways related to CI and involved in curcumin's protective activity against mixed heavy metals such as "apoptosis multiple species", "apoptosis", and "Alzheimer's disease". We also created and tested in silico sponges that inhibited these miRNAs. Curcumin's physicochemical characteristics and pharmacokinetics are consistent with its therapeutic benefits in CI, owing to its high gastrointestinal absorption and ability to cross the blood-brain barrier, and it is not a P-glycoprotein substrate. Our findings emphasize the protective effects of curcumin in CI caused by heavy metal mixtures and pave the way for molecular mechanisms involved in CI pathology.