Hepatoprotective potential of Diospyros melanoxylon (Roxb.) leaf extract by inhibition of IL-6, COX-2, and 5-LOX expression in paracetamol intoxicated rats

Ethnopharmacological relevance Diospyros melanoxylon, Roxb., (Ebenaceae), native to South and Southeast Asia, has been traditionally used to treat liver disorders, jaundice, tuberculosis, and chronic wounds and inflammatory conditions. Aim of the study To evaluate the hepatoprotective effect of D. melanoxylon leaf methanolic extract (MDML) in paracetamol (PCM)-induced liver toxicity in rats. Material and method Phytoconstituents in the MDML were identified via LC-MS. Molecular docking and dynamics simulations evaluated the binding stability of ursolic acid (UA) with IL-6, COX-2, and LOX. In vitro COX-2 and 5-LOX inhibition assays assessed anti-inflammatory potential. Hepatoprotective efficacy was examined in PCM-intoxicated rats treated with MDML (200, 300, 400 mg/kg). Biochemical markers, serum enzymes (ALT, AST, ALP, GGT, LDH), protein profile (TP, ALB, GLB, TB), antioxidant enzymes (SOD, CAT, GSH), oxidative stress marker (MDA), and cytokines (IL-6, IL-10, IL-1β, TNF-α) were analyzed. Histopathological examination of liver tissues further validated the findings. Result Nineteen compounds were identified by LC-MS. UA showed strong docking affinities with IL-6 (-7.0 kcal/mol), COX-2 (-8.5 kcal/mol), and LOX, with MD simulations confirming stable interactions. MDML (400 μg/mL) inhibited COX-2 and 5-LOX by 78.45 % and 85.45 %, respectively. In vivo, MDML (400 mg/kg) significantly (p Conclusion MDML shows dose-dependent hepatoprotection against PCM-induced toxicity, likely due to the presence of UA, supporting its traditional use in liver disorders.