Evaluation of Umbelliferone Neuroprotective Effects Against Acrylamide-Induced Oxidative Stress, In Vivo and In Silico Study

Acrylamide (ACR) is a heat-generated carcinogen, one of the most common toxins, with various effects on the biological system, including oxidative stress and related disorders. Umbelliferone (UMB) is a naturally occurring coumarin derivative that is present in edible fruits, known as an antioxidant, and reported for many other therapeutic effects. In the current study, UMB was evaluated for neuro- and hepatoprotective activity against oxidative stress toxicity induced by a 40 mg/kg daily dose of ACR in a mouse model over 15 days. Also, UMB was used as a ligand for the first time to predict its affinity for the most important proteins involved in neuronal failure. The UMB administration significantly improves liver enzyme elevations, alanine transaminase (ALT) and aspartate transaminase (AST), following ACR injection. Also, UMB treatment reduced elevated total protein (TP) and albumin (ALB) serum levels. In addition, lipid peroxidation levels were significantly reduced by UMB (expressed as malondialdehyde MDA levels), and the levels of total non-enzymatic antioxidant capacity (TAC) were increased in brain tissue homogenate in comparison with brain injury in the ACR group. Furthermore, UMB downregulated the expression of tumor necrosis factor-alpha (TNF-α), an inflammatory marker and caspase-3, an apoptotic marker, while upregulating heme oxygenase-1 (HO-1), an antioxidant enzyme, in both liver and brain tissues. Molecular docking analysis revealed that the compound could form H-bonds and hydrophobic interactions with the target receptors. Results of this study conclude that UMB may be considered a potential pharmaceutical agent to ameliorate ACR-induced toxicity in the liver and brain, due to its anti-inflammatory, antioxidant, and antiapoptotic mechanisms, as well as its moderate affinity for neuronal disease-targeted proteins.