Neuroprotective and cognitive-enhancing effects of γ-Oryzanol in bile duct ligation-induced hepatic encephalopathy in rats.

Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome characterized by a spectrum of symptoms ranging from mild cognitive and motor disturbances to severe coma. γ-Oryzanol (ORY), a natural compound derived from rice bran, has demonstrated potential to enhance memory and cognitive function in preclinical studies. This study investigated the neuroprotective and cognitive-enhancing effects of γ-oryzanol in a rat model of HE induced by bile duct ligation (BDL). Male Wistar rats underwent BDL surgery and received either γ-oryzanol (100 mg/kg) or vehicle via oral gavage for subchronic 28 days. Four experimental groups were included: sham-operated, sham + ORY, BDL, and BDL + ORY. Cognitive function was assessed using the Novel Object Recognition (NOR) test and Y-maze. Blood samples were analyzed for oxidative stress markers (antioxidant status, lipid peroxidation, thiol levels), liver function markers (bilirubin, albumin, AST, ALT, ALP, LDH), and prefrontal cortex tissues were examined histologically. BDL induction significantly impaired cognitive performance and increased oxidative stress and neuronal damage in the prefrontal cortex. γ-Oryzanol treatment effectively restored cognitive function, reduced oxidative stress, and attenuated neuronal damage without significantly altering liver enzyme levels. These findings suggest that γ-oryzanol exerts neuroprotective effects in HE possibly through antioxidant-related pathways, although this mechanism was not consistently supported by all oxidative stress markers. The protective effects appeared largely independent of major liver function improvement.