Computational assessment of the biological response of curcumin to type 2 diabetes mellitus induced by metal exposure.

The current study aimed to identify the molecular mechanisms of a metal mixture (cadmium, nickel, and lead) involved in type 2 diabetes mellitus (T2DM) development and the therapeutic effect of curcumin in this metal mixture-induced T2DM. To accomplish this, SwissADME assessed the physicochemical and pharmacokinetic properties of curcumin and the Prediction of Activity Spectra for Substances evaluates its biological activities. The Comparative Toxicogenomics Database, Cytoscape, AutoDock Vina, and MicroRNA ENrichment TURned NETwork were used as tools to perform data-mining approaches and molecular docking. Curcumin properties were fitted within the acceptable range to be a promising drug candidate. The mixed metal altered 23 genes linked to T2DM development and targeted by curcumin. Curcumin had a dual-natured effect or antagonistic effect for most of the involved genes in T2DM and metal mixture. The most prominent biological processes were identified as ''response to external stimulus'', ''regulation of programmed cell death'', ''programmed cell death'', ''cell death'', and ''response to stress''. Three highly interacted miRNAs related to metal mixture-induced T2DM and targeted by curcumin (hsa-miR-98-5p, hsa-miR-34a-5p, and hsa-miR-155-5p) were identified. These findings could pave the way for further studies to evaluate the link between these genes and T2DM.