Neuroprotective effects of honokiol against hexavalent chromium exposure in rat brain: Evidence from oxidative stress, inflammation, and apoptosis.

Hexavalent chromium (Cr-VI) is a major industrial and environmental pollutant with serious toxicological and health consequences worldwide. Limited knowledge about its neurotoxic potential and the underlying mechanisms. Honokiol (Hnk) is a bioactive neolignan compound derived from Magnolia species with reported neuroprotective properties. The present study aimed to investigate the protective effects of Hnk against Cr-VI-induced neurotoxicity in rats. Forty male Wistar Albino rats were allocated into five groups (n = 8): Control, vehicle, Cr-VI (15 mg/kg), Hnk (40 mg/kg), and Cr-VI + Hnk (15 mg/kg Cr-VI and 40 mg/kg Hnk). All treatments were administered orally once daily for 15 days. In the brain tissue of Cr-VI group, elevated levels of malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and interleukin-1β (IL-1β) were noted, whereas GSH levels and the activities of superoxide dismutase (SOD), catalase (CAT), and acetylcholinesterase (AChE) were decreased. Hnk treatment decreased MDA levels while increasing GSH levels and SOD, CAT, and AChE activities, and reduced TNF-α and IL-1β levels. Immunohistochemical investigations demonstrated that Cr-VI raised the cerebral cortex and hippocampus expression of the endoplasmic reticulum stress (ERS) marker C/EBP homologous protein (CHOP), the apoptotic marker caspase-3, and the astroglial activation marker glial fibrillary acidic protein (GFAP). Hnk treatment reduced these expressions. Histopathological alterations caused by Cr-VI improved in Hnk-treated groups. The Cr-VI group exhibited a reduced number of neurons in the cornu ammonis and dentate gyrus. Hnk therapy was observed to mitigate this neuronal loss. In conclusion, Hnk reduces Cr-VI-induced neurotoxicity by lowering oxidative stress, neuroinflammation, ERS, apoptosis, and glial activation, preserving tissue integrity.