Trigonelline protects against alcohol-induced brain damage by inhibition of oxidative stress, TLR۴/NF-κB/proinflammatory cytokines pathway, and apoptosis

Objective(s): Brain injury is one of the most predominant complications following excessive alcohol consumption. Oxidative, inflammatory, and apoptotic processes are the essential mechanisms involved in alcohol-induced brain damage. Trigonelline is a natural compound that has a variety of pharmacologic activities. The present study investigated the protective effect of trigonelline in alcohol-induced brain injury and its underlying mechanisms.  Materials and Methods: Adult male mice (C۵۷BL/۶) were exposed to binge ethanol (۶ g/kg/day, by gavage) and treated with trigonelline (۵۰ and ۱۰۰ mg/kg/day, orally) for ۶ days. Mice were sacrificed and the brain tissues were dissected for experimental assessments.  Results: The results showed that trigonelline alleviated alcohol-induced locomotor impairment and brain oxidative damage by decreasing lipid peroxidation and protein oxidation. Trigonelline restored the levels of protective antioxidants (GSH, SOD, and HO-۱) and reduced the levels of ICAM-۱ and MPO in the brains of mice exposed to alcohol. Trigonelline significantly reduced alcohol-induced brain inflammation by the inhibition of iNOS/NO, TLR۴, NF-κB, and proinflammatory cytokines (TNF-α, IL-۶, IL-۱β, and TGF-β۱). Moreover, trigonelline treatment reduced the levels of caspase-۳, cytochrome c, and TUNEL positive cells in the brains of alcohol-exposed mice. Conclusion: These findings suggest that trigonelline protects brain against alcohol intoxication by inhibition of oxidative and inflammatory and apoptotic responses. Therefore, trigonelline may serve as a potential therapeutic approach for the protection of brain damage associated with binge alcohol consumption.

کلیدواژه ها:

Alcohol ، Neuroinflammation ، Neurotoxicity ، TLR۴/NF-κB ، Trigonelline