Trigonelline protects against alcohol-induced brain damage by inhibition of oxidative stress, TLR4/NF-κB/proinflammatory cytokines pathway, and apoptosis.

OBJECTIVES: 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 (C57BL/6) were exposed to binge ethanol (6 g/kg/day, by gavage) and treated with trigonelline (50 and 100 mg/kg/day, orally) for 6 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-1) and reduced the levels of ICAM-1 and MPO in the brains of mice exposed to alcohol. Trigonelline significantly reduced alcohol-induced brain inflammation by the inhibition of iNOS/NO, TLR4, NF-κB, and proinflammatory cytokines (TNF-α, IL-6, IL-1β, and TGF-β1). Moreover, trigonelline treatment reduced the levels of caspase-3, 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.