Hepatoprotective activity of praecoxin A isolated from Melaleuca ericifolia against carbon tetrachloride-induced hepatotoxicity in mice. Impact on oxidative stress, inflammation, and apoptosis

The hepatoprotective activity of praecoxin A, an ellagitannin from Melaleuca ericifolia, was determined against CCl4-induced toxicity in mice. Praecoxin A was administered (25, 50, and 100 mg/kg) for 5 days followed by CCl4. Praecoxin A markedly ameliorated the CCl4-induced increase in AST (by 19, 52, and 56%), ALP (22, 45, and 48%), ALT (11, 47, and 54%), total bilirubin (14, 27, and 28%), and MDA (26, 44, and 51%) at the tested doses, respectively, as compared with CCl4 group. It was evident that praecoxin A significantly (p < 0.001) increased the antioxidant parameters GSH (45, 99, and 137%) and SOD (61, 129, and 159%). Histological findings revealed a marked amelioration of hepatocyte degeneration, necrosis, inflammatory cell infiltration, and hemorrhage in the groups treated with praecoxin A. COX-2 and caspase-3 hepatic expressions were significantly downregulated (p < 0.001) in praecoxin A-treated groups (up to 57, 83, and 93% for COX-2 and by 30, 82, and 99% for caspase-3). These findings suggest that praecoxin A exerts a beneficial effect against oxidative stress by reducing lipid peroxidation, enhancing the antioxidant defense status, and protecting against the histopathological changes induced by CCl4. This study highlights a promising natural hepatoprotective candidate derived from M. ericifolia that might be an alternative to silymarin.