Protective effects of Fraxinus Micrantha against thioacetamide-induced hepatic encephalopathy: a focus on antioxidant and neuroprotective mechanisms.

Hepatic encephalopathy (HE) is a multifaceted neuropsychiatric syndrome frequently observed in patients with liver dysfunction. The present study aimed to evaluate the therapeutic effects of Fraxinus micrantha (F. micrantha) in thioacetamide (TAA)-induced HE model. HE was induced using TAA (200 mg/kg i.p.) for once every 48 h for 14 consecutive days in rats. Ethyl acetate fraction of F. micrantha (EAFM) (50, 100, and 200 mg/kg) was administered for 14 consecutive days (p.o.) after HE induction. TAA induced hepatotoxicity and HE, evidenced by significant alterations in liver biomarkers alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), lipid profiles (triglycerides, cholesterol), and neurotransmitter levels (serotonin, acetylcholine, dopamine, norepinephrine). Histopathological analysis revealed severe liver necrosis, inflammation, and brain damage, characterized by reduced neuronal density and hippocampal degeneration. EAFM treatment produced a significant, dose-dependent amelioration of TAA-induced liver injury, evidenced by the normalization of serum biomarkers (ALT, AST, ALP) and lipid profiles (cholesterol, triglycerides), with the 200 mg/kg dose showing efficacy comparable to silymarin. EAFM also exerted potent neuroprotective effects, restoring the altered levels of key neurotransmitters (serotonin, dopamine, norepinephrine) and reducing elevated acetylcholinesterase activity in the brain cortex and hippocampus. Furthermore, EAFM significantly mitigated oxidative stress by replenishing depleted reduced glutathione (GSH) levels in both hepatic and brain tissues. Histopathological analysis confirmed these findings, demonstrating that EAFM attenuated TAA-induced hepatocellular necrosis, inflammation, and hippocampal neurodegeneration. The results indicate that F. micrantha confers robust hepatoprotective and neuroprotective effects against HE, primarily mediated through its antioxidant activity and restoration of neurochemical balance, positioning it as a promising therapeutic candidate.