Hypericum perforatum Reduces Paracetamol‐Induced Hepatotoxicity and Lethality in Mice by Modulating Inflammation and Oxidative Stress

Hypericum perforatum is a medicinal plant with anti‐inflammatory and antioxidant properties, which is commercially available for therapeutic use in Brazil. Herein the effect of H. perforatum extract on paracetamol (acetaminophen)‐induced hepatotoxicity, lethality, inflammation, and oxidative stress in male swiss mice were investigated. HPLC analysis demonstrated the presence of rutin, quercetin, hypericin, pseudohypericin, and hyperforin in H. perforatum extract. Paracetamol (0.15–3.0 g/kg, p.o.) induced dose‐dependent mortality. The sub‐maximal lethal dose of paracetamol (1.5 g/kg, p.o.) was chosen for the experiments in the study. H. perforatum (30–300 mg/kg, i.p.) dose‐dependently reduced paracetamol‐induced lethality. Paracetamol‐induced increase in plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations, and hepatic myeloperoxidase activity, IL‐1β, TNF‐α, and IFN‐γ concentrations as well as decreased reduced glutathione (GSH) concentrations and capacity to reduce 2,2′‐azinobis‐(3‐ethylbenzothiazoline‐6‐sulfonate radical cation; ABTS˙⁺) were inhibited by H. perforatum (300 mg/kg, i.p.) treatment. Therefore, H. perforatum protects mice against paracetamol‐induced lethality and liver damage. This effect seems to be related to the reduction of paracetamol‐induced cytokine production, neutrophil recruitment, and oxidative stress. Copyright © 2015 John Wiley & Sons, Ltd.