Pterostilbene Exerts Hepatoprotective Effects through Ameliorating LPS/D-Gal-Induced Acute Liver Injury in Mice

Acute liver injury (ALI) refers to abnormalities in liver function caused by various causes and accompanied by poor prognosis and high mortality. Common predisposing factors for the disease are viral hepatitis, bacteria, alcohol, and certain hepatotoxic drugs. Inflammatory response and oxidative stress are critical for the pathogenesis of ALI. Pterostilbene (Pte), a natural polyphenol product extracted from blueberries and grapes, has been reported that exerted multiple biological activities, including antioxidative, anti-inflammatory, anti-carcinogenic, and anti-apoptotic properties. However, there is very little data showing the hepatoprotective effect of Pte on lipopolysaccharide/D-galactosamine (LPS/D-Gal)-induced ALI in mice. In this study, the possible protective effect and potential mechanisms of Pte on ALI are being investigated. It has been found that Pte markedly ameliorates LPS/D-Gal-induced inflammatory infiltration, hemorrhage, and dissociation of the hepatic cord, reducing the myeloperoxidase (MPO) activity in liver tissues and serum levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) in ALI. Pte also inhibits LPS/D-Gal-induced secretion of pro-inflammatory cytokine tumor necrosis factor-a (TNF-α), interleukin 6 (IL-6), and interleukin 1β (IL-1β) in liver tissues. Furthermore, the western blot analysis reveals that LPS/D-Gal-activated nuclear factor-kappa B (NF-κB) is significantly inhibited by Pte, and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase-1 (HO-1) are upregulated by Pte. In conclusion, our results suggest that Pte exerts anti-inflammatory and antioxidative effects, which might contribute to ameliorating LPS/D-Gal-induced ALI in mice. Pte has the potential to be a preventive hepatoprotective agent.