Pakistan Journal of Pharmaceutical Sciences

Abstract: Prolonged exposure to iron can result in severe hepatic complications such as chronic liver damage, jaundice, cirrhosis, and hepatocellular carcinoma. Current treatment options for metal-induced hepatotoxicity are limited and often associated with undesirable side effects. This study investigates the hepatoprotective and anti-inflammatory properties of three phytochemicals, albiziasaponin-A, ellagitannin and azadirachtin, against iron-induced liver toxicity. Both in silico and in vivo approaches were employed to assess their binding affinity as well as the therapeutic effects of selected phytochemicals against the target protein, cyclooxygenase-2, a marker of liver damage. Molecular docking revealed strong binding affinities of all compounds with COX-2, indicating promising anti-inflammatory potential. Hepatic injury was assessed through biomarkers including ALT, 4HNE, 8-OHdG, TNF-?, IsoP-2?, MDA, and COX-2 levels. The rat group exposed to iron overdose exhibited significantly elevated biomarker levels compared to controls, confirming hepatotoxicity. However, combination therapy with the selected phytochemicals led to a significant reduction in these biomarkers, suggesting effective hepatoprotection. These findings indicate that albiziasaponin-A, ellagitannin and azadirachtin possess potent therapeutic properties that may be beneficial in mitigating iron-induced liver damage. Further investigation is needed to establish their potential for inclusion in novel drug formulations targeting inflammatory liver diseases.