Objective: Hydroxytyrosol (HT) is a polyphenol with a wide range of biological activities. Excessive drinking can lead to oxidative stress and inflammation in the liver, which usually develop into alcohol liver disease (ALD). At present, there is no specific drug to treat ALD. In this paper, the protection effect of HT on ALD and the underline mechanism were studied.Methods: HepG2 cells were exposed to ethanol in vitro and C57BL/6J mice were fed with a Lieber-DeCarli ethanol liquid diet in vivo.Results: triglyceride (TG) level in serum and the expression of fatty acid synthase (FASN) were reduced significantly by the treatment with HT The acetaldehyde dehydrogenase (ALDH) activity was increased, the serum level of malondialdehyde (MDA) was decreased, catalase (CAT) and glutathione (GSH) were increased, suggesting that HT may reduce its oxidative damage to the body by promoting alcohol metabolism. Furthermore, according to the mRNA levels of tnf-α, il-6 and il-1β, HT inhibited ethanol-induced inflammation significantly. The anti-inflammatory mechanism of HT may be related to suppress the STAT3/iNOS pathway.Dissussion: Our study showed that HT could ameliorate ethanol-induced hepatic steatosis, oxidative stress and inflammation and provide a new candidate for the prevention and treatment of ALD.
Keywords: ADH, alcohol dehydrogenase; ALD, alcohol liver disease; ALDH, acetaldehyde dehydrogenase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CAT, catalase; COX2, cyclo-oxygen-ase2; CYP2E1, cytochrome P450 2E1; DMSO, Dimethyl sulfoxide; DPPH, 2,2-Diphenyl-1-picrylhydrazyl; FASN, fatty acid synthase; GSH, glutathione; HT, hydroxytyrosol; HepG2; Hepatic steatosis; Hydroxytyrosol; LDL, low density lipoprotein; LPS, lipopolysaccharides; Liver injury; MDA, malondialdehyde; NO, nitric oxide; PPAR-γ, peroxisome proliferators-activated receptor; ROS, reactive oxygen species; SREBP-1c, sterol regulatory element-binding protein-1c; STAT3, signal transducer and activator of transcription 3; STAT3/iNOS pathway; TC, total cholesterol; TG, triglyceride; alcoholic liver disease; anti-inflammation; anti-oxidation; iNOS, inducible nitric oxide Synthas.