Inhibition of PI3K/Akt/mTOR/JAK-2/STAT-3 Signalling Pathways via Ligustrazine in Alcoholic Liver Disease Associated Neurological Dysfunction.

Alcoholic liver disease (ALD) is a prevalent chronic hepatic disorder characterized by the abnormal accumulation of fat in the liver. Current treatments for ALD primarily focus on liver function and metabolic concerns; however, emerging evidence suggests that the disease also affects the brain, resulting in cognitive and mood disturbances. Individuals with ALD frequently encounter difficulties with memory, attention, executive function, mood, and episodes of depression. Excessive alcohol consumption is often employed to replicate ALD-related neurological impairments in preclinical studies. Ligustrazine has demonstrated therapeutic potential in this regard. An ethanol binge combined with CCl4 induced neurological complications in Sprague-Dawley rats associated with ALD. Neurobehavioral changes were evaluated, and molecular docking, behavioural analysis, cellular and molecular signalling, biochemical assessments, gross morphological examinations, and histopathological evaluations were conducted to determine the efficacy of ligustrazine compared with prednisolone. Ligustrazine modulated key molecular signalling pathways in both brain and liver homogenates and improved neurobehavioral, biochemical, and histopathological parameters in treated rats. Ligustrazine exhibits significant neuroprotective and hepatoprotective properties in neurological conditions associated with ALD. Additional clinical and experimental investigations are required to validate its therapeutic efficacy. These findings endorse the advancement of targeted biomarker-based therapies to enhance outcomes for patients with ALD-related neurological disorders.