Characterisation of Hepatoprotective Mechanisms of Moringa oleifera Leaf Polyphenols Against Acetaminophen-Induced Hepatotoxicity in Rats

Acetaminophen overdose-induced hepatotoxicity is mediated through oxidative stress, mitochondrial dysfunction, and inflammatory cascades, and plant polyphenols with antioxidant and anti-inflammatory properties have been proposed as candidates for hepatoprotective interventions. This study characterises the hepatoprotective mechanisms of Moringa oleifera leaf polyphenol-rich extract against acetaminophen-induced hepatotoxicity in Wistar rats. Forty rats were divided into five groups: normal control, acetaminophen hepatotoxicity control (600 mg/kg oral), silymarin reference treatment (100 mg/kg), low-dose Moringa polyphenol extract (250 mg/kg), and high-dose extract (500 mg/kg). Hepatotoxicity was induced by a single oral dose of acetaminophen, and treatment extracts were administered for seven days prior to induction and for two days post-induction. Serum liver function enzymes, bilirubin, albumin, and prothrombin time were measured. Liver tissue was analysed for oxidative stress markers (MDA, SOD, CAT, GPx, GSH), inflammatory cytokines (TNF-alpha, IL-6, IL-1beta) by ELISA, and hepatocyte apoptosis by caspase-3 activity. Histopathology was performed by haematoxylin-eosin and Masson's trichrome staining. The high-dose extract significantly attenuated acetaminophen-induced elevation of serum ALT, AST, and ALP, and reduced bilirubin towards normal ranges. Tissue analysis revealed significant reduction in MDA, TNF-alpha, IL-6, and caspase-3 activity in extract-treated groups, alongside preservation of antioxidant enzyme activities. Histopathology confirmed reduced necrotic area and inflammatory cell infiltration. These results indicate that Moringa polyphenols protect hepatocytes through coordinated antioxidant, anti-inflammatory, and anti-apoptotic mechanisms. Keywords: Moringa oleifera, hepatoprotection, acetaminophen toxicity, polyphenols, oxidative stress.