Resveratrol, Endocrine Disrupting Chemicals, Neurodegenerative Diseases and Depression: Genes, Transcription Factors, microRNAs, and Sponges Involved.

Abstract

We aimed to examine the molecular basis of the positive effect of resveratrol against amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), cognitive impairment (CI), and depression induced by a mixture of bisphenol A (BPA), BPS, and BPF. The CTD, GeneMania, Metascape, SwissADME, Cytoscape, MIENTURNET, miRNAsong, and Autodock Vina were the fundamental tools for analysis. Resveratrol exerts its protective effects on selected diseases induced by a mixture of BPA, BPS, and BPF through the following genes: PTGS2 and GSR for ALS; INS, IL6, BDNF, and SOD1 for PD; BDNF, CASP3, TNF, INS, IGF1, IL1B for CI; and BDNF, PTGS2, and IL6 for depression. Detoxification was noted as the most important for ALS, dopamine metabolism for PD, apoptosis for CI, and the selenium micronutrient network for depression. hsa-miR-377-3p, hsa-miR-1-3p, hsa-miR-128-3p, and hsa-miR-204-5p were highlighted. We created and tested in silico sponges that inhibited these miRNAs. NFE2L2, BACH1, PPARG, and NR4A3 were listed as the key transcription factors implicated in resveratrol's protective effect against harmful studied chemicals. Furthermore, resveratrol's physicochemical properties and pharmacokinetics are consistent with its therapeutic benefits in ALS, PD, CI, and depression, owing to its high gastrointestinal absorption, drug-likeness, non-P-glycoprotein substrate, and capacity to penetrate the blood-brain barrier.