Hawthorn (HAW) is a herbal preparation extracted from Crataegus oxyacantha. HAW has cardioprotective, antioxidants, anti-inflammatory, and anti-hypotensive effects. HAW’s effect on hepatic fibrosis remains, however, unknown. This study evaluated the impact of HAW on carbon tetrachloride (CCl4)-induced hepatic fibrosis in rats and elucidated its mechanisms. HAW reduced liver index and the serum liver enzyme markers and reduced liver damage, and fibrosis as confirmed by histopathological scoring of hematoxylin-eosin staining. Collagen deposition was reduced in HAW group compared to CCl4 group as confirmed by Masson staining, hydroxyproline content, and both mRNA and protein levels of alpha-smooth muscle actin, collagen 1 and 3. HAW also down regulated the gene expressions of inflammatory markers including interleukin-IL-1β, tumor necrosis factor-α, transforming growth factor-β 1, nuclear factor kappa-B, and cyclooxygenase-2 and decreased the myeloperoxidase activity. The effects of HAW was also associated with decreased levels of hepatic oxidative stress markers (malondialdehyde and P.Carbonyl) and with increased activity of superoxide dismutase. Those effects are possibly mediated by blocking the pro-oxidant machinery and down regulating the inflammatory and profibrotic responses. Finally, chlorogenic acid, epicatechin, rutin, vitexin quercetin, and iso quercetin were identified as the major species of polyphenols of the HAW herbal preparation used here. Therefore, HAW’s potent protecting effects against liver fibrosis predicts a significant beneficial application.

Background Ketoconazole (KET) is a broad-spectrum antifungal drug that has been reported to induce hepatotoxicity in humans and animals. Methods The safe guarding response of Gentiana extract (GEN) against KET-induced hepatotoxicity was investigated in this study using male Wistar rats. GEN ethanol extract was orally administered to rats (1 g/kg b.wt) for 30 days. Beginning on day 26, KET was intraperitoneally administered once daily for 5 days using a dose of 100 mg/kg. The hepatoprotective effects of GEN against liver damage induced by KET were monitored through significant decrements in serum levels of aminotransferase and alpha-fetoprotein as well as recorded hepatic histopathological changes. Results The hepatotoxicity of KET treatment was accompanied with a marked oxidative damage to hepatic proteins, lipids, and DNA, and depletions in natural antioxidants (glutathione and superoxide dismutase). GEN inhibited KET-induced oxidative stress by diminishing lipid peroxidation, protein carbonylation, and oxidative stress in DNA. These free radical mediated effects were greatly decreased with GEN treatment. Conclusions This study suggests that GEN’s hepatoprotective effects could be attributed to its antioxidant properties.