Umbelliferone ameliorates acrylamide-induced brain damage by attenuating oxidative stress, inflammation, and apoptosis and restoring Nrf2/HO-1 in mice

Umbelliferone (UF), a natural coumarin derivative, possesses antioxidant and anti-inflammatory actions. Acrylamide (ACR) is a known neurotoxic compound that induces oxidative stress, inflammation, and apoptotic cell death, contributing to neurotoxic damage. This study aimed to assess the potential neuroprotective effects of UF against ACR-induced brain damage in mice. Mice received UF (25 or 50 mg/kg, orally) for 14 days, followed by ACR (50 mg/kg, intraperitoneally) for the last 11 days. ACR exposure significantly increased malondialdehyde and protein carbonyl contents and decreased reduced glutathione levels and superoxide dismutase and catalase activities in the brain. Hematoxylin and eosin staining assessments revealed pronounced histological alterations in the brains of ACR-injected animals, indicating severe neurotoxic damage. The brains of ACR-administrated animals also showed increased nuclear factor-kappa B (NF-κB) p65 expression and elevated tumor necrosis factor-alpha and interleukin-1β levels. ACR exposure resulted in significantly increased Bax and caspase-3 levels and decreased Bcl-2 levels in the brain. Overall, UF treatment ameliorated histopathological changes, mitigated oxidative stress, enhanced cellular antioxidants, suppressed NF-κB p65 and inflammatory mediators, modulated apoptotic markers (Bcl-2, Bax, and caspase-3), and restored Nrf2/HO-1 in the brain. In conclusion, UF exerts significant neuroprotective effects against ACR-induced brain injury by modulating Nrf2/HO-1 signaling and mitigating inflammation, oxidative stress, and apoptosis. These findings suggest that UF may represent promising neuroprotective effects against ACR-induced neurotoxicity and potentially other brain injuries driven by oxidative stress and inflammation.