Oxyresveratrol prevents lipopolysaccharide/d-galactosamine-induced acute liver injury in mice

• Published in: International immunopharmacology Vol. 56; pp. 105 - 112
• Main Authors: Jia, Ya-Nan, Lu, Hai-Peng, Peng, Ya-Lin, Zhang, Bao-Shun, Gong, Xiao-Bao, Su, Jun, Zhou, You, Pan, Min-Hui, Xu, Li
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2018; Elsevier BV
• Subjects: 1-Phosphatidylinositol 3-kinase; Activation; Acute liver injury; AKT protein; Alanine; Alanine transaminase; Animals; Anti-apoptosis; Anti-Inflammatory Agents - therapeutic use; Apoptosis; Aspartate transaminase; B-cell lymphoma; Bax protein; Bcl-2 protein; Cells, Cultured; Chemical and Drug Induced Liver Injury - drug therapy; Chemical compounds; Cytokines; D-Galactosamine; Galactosamine - immunology; Heme; Heme Oxygenase-1 - metabolism; Hepatocytes - drug effects; Hepatocytes - physiology; Immune system; Inflammation; Injury prevention; Keap1-Nrf2; Kelch-Like ECH-Associated Protein 1 - metabolism; Lipopolysaccharide/d-galactosamine; Lipopolysaccharides; Lipopolysaccharides - immunology; Liver; Liver - drug effects; Liver - metabolism; Liver - pathology; Lymphocytes B; Lymphoma; Male; Membrane Proteins - metabolism; Mice; Mice, Inbred Strains; Morus - immunology; NAD(P)H Dehydrogenase (Quinone) - metabolism; NF-E2-Related Factor 2 - metabolism; NF-kappa B - metabolism; NF-κB protein; Oxidative stress; Oxidoreductase; Oxygenase; Oxyresveratrol; Pharmacology; Plant Extracts - therapeutic use; Product inhibition; Proteins; Quinine; Rodents; Signal transduction; Signal Transduction - drug effects; Signaling; Stilbenes - therapeutic use; TLR4 protein; TLR4/NF-κB; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Oxyresveratrol; Keap1-Nrf2; Anti-apoptosis; Acute liver injury; Lipopolysaccharide/d-galactosamine; TLR4/NF-κB
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2018.01.014

Oxyresveratrol (Oxy) is a natural polyhydroxystilbene abundant in mulberry that has anti-inflammation and anti-oxidant activities. We evaluated the protective effect of Oxy in the context of the lipopolysaccharide and d-galactosamine (LPS/d-GalN) induced acute liver injury. Oxy restricted the development of histopathological changes, markedly reduced the activity of alanine transaminase (ALT) and aspartate transaminase (AST), which are indicators of impaired liver function. Oxy significantly regulated the contents of oxidative stress related enzymes and products, and inhibited expressions of inflammatory mediators and cytokines. Oxy treatment diminished the Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway in liver, activated the Kelch-like ECH-associated protein 1(Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, and increased expressions of heme oxygenase 1 (HO-1) and quinine oxidoreductase 1(NQO1). Pretreatment with Oxy decreased LPS/d-GalN stimulated hepatocyte apoptosis by efficaciously raising the B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X (Bax) ratio, inhibiting the expression and activation of caspases, and activating the phosphoinoside-3-kinase (PI3K)-Akt pathway. Our results demonstrate the hepatoprotective efficacy of Oxy. The protection is mainly due to the prevention of TLR4/NF-κB pathway activation, induced activation of Keap1-Nrf2 signaling pathway, and decreased hepatocyte apoptosis. Oxy warrants further study as a potential therapeutic agent candidate for the management of acute liver injury. [Display omitted] •Oxy protects mice from LPS/d-GalN-induced acute liver injury.•Oxy inhibits the activation of TLR4/NF-κB pathway in liver.•Oxy mitigates oxidative stress in liver by regulating the Keap1-Nrf2 pathway•Oxy exerts the inhibition on hepatocyte apoptosis in mice.