Protective effects of morin on lipopolysaccharide/d-galactosamine-induced acute liver injury by inhibiting TLR4/NF-κB and activating Nrf2/HO-1 signaling pathways.

Morin, a bioactive flavonoid extracted from the bark of Moraceae plants and many medicinal herbs, has anti-inflammatory and antioxidative effects. In this research, we explored the protective effects of morin against lipopolysaccharide (LPS) and d-galactosamine (D-GalN) induced acute liver injury in mice. Mice were given an intraperitoneal injection of morin before LPS and D-GalN treatment and the HepG2 cells were only given morin to investigate its effects. The results showed that morin markedly inhibited the production of serum alanine transaminase (ALT), aspartate aminotransferase (AST), interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and hepatic TNF-α, IL-6, and myeloperoxidase (MPO) induced by LPS/D-GalN. In order to evaluate morin effect in the future, we investigated the expression of nuclear factor E2 related factor 2 (Nrf2), nuclear factor-kappaB (NF-κB), toll like receptor 4 (TLR4) on liver injury. Taken together, these results suggested that morin could exert the anti-inflammatory and anti-oxidative effects against LPS/D-GalN-induced acute liver injury by activating Nrf2 signal pathways and inhibiting NF-κB activation.

Tian Y ，Li Z ，Shen B ，Zhang Q ，Feng H ... -  《-》

Andrographolide ameliorates d-galactosamine/lipopolysaccharide-induced acute liver injury by activating Nrf2 signaling pathway.

Pan CW ，Yang SX ，Pan ZZ ，Zheng B ，Wang JZ ，Lu GR ，Xue ZX ，Xu CL ... -  《Oncotarget》

Protective effect of oroxylin A against lipopolysaccharide and/or D-galactosamine-induced acute liver injury in mice.

Oroxylin A, a natural flavonoid isolated from Scutellariae baicalensis, has been reported to possess a wide spectrum of pharmacologic activities. However, the effects of oroxylin A on liver injury are poor understood. The purpose of this study was to investigate the effects of oroxylin A on acute liver injury in mice induced by lipopolysaccharide and/or D-galactosamine (LPS and/or D-GalN). Mice acute liver injury model was induced by LPS (50 μg/kg) and/or GalN (800 mg/kg). Serum alanine aminotransferase, aspartate aminotransferase, and tumor necrosis factor-α levels, hepatic tissue histology, malondialdehyde content, and myeloperoxidase activity were analyzed. Meanwhile, nuclear factor kappa B (NF-κB), heme oxygenase-1 (HO-1), and nuclear factor erythroid2-related factor 2 (Nrf2) expression were detected by Western blotting. The results showed that oroxylin A dose-dependently inhibited LPS and/or GalN-induced serum alanine aminotransferase, aspartate aminotransferase, and tumor necrosis factor-α levels. Hepatic malondialdehyde content and myeloperoxidase activity were also suppressed by oroxylin A. We also found that oroxylin A inhibited LPS and/or GalN-induced toll like receptor 4 (TLR4) expression and NF-κB activation. In addition, oroxylin A upregulated the expression of Nrf2 and HO-1 in a dose-dependent manner. In conclusion, oroxylin A protected against LPS and/or GalN-induced liver injury through activating Nrf2 and inhibiting TLR4 signaling pathway.

Huang H ，Zhang X ，Li J 《-》

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

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.

Jia YN ，Lu HP ，Peng YL ，Zhang BS ，Gong XB ，Su J ，Zhou Y ，Pan MH ，Xu L ... -  《-》

Protective effects of sea buckthorn polysaccharide extracts against LPS/d-GalN-induced acute liver failure in mice via suppressing TLR4-NF-κB signaling.

Sea buckthorn (Hippophae rhamnoides L.) berries have been traditionally used to treat gastric disorders, cardiovascular problems, and liver injuries in oriental medicinal system. This study aimed to explore the protective effects and mechanisms of the polysaccharide extracts of Sea buckthorn (HRP) berries against lipopolysaccharide (LPS) and d-galactosamine hydrochloride (d-GalN)-induced acute liver failure in mice. HRP was isolated by hot-water extraction and characterized by HPLC and infrared spectrum analysis. The total carbohydrate, uronic acid and protein contents of HRP were measured by a spectrophotometric method. Mice were orally administrated with HRP (50, 100, 200mg/kg) once daily for 14 consecutive days prior to the challenge with LPS (50 μg/kg) and d-GalN (300 mg/kg). Animals of positive control group were intraperitoneally injected with dexamethasone (10mg/kg). Mice were sacrificed at 8h after LPS/d-GalN injection. Pretreatment with HRP significantly inhibited LPS/d-GalN-induced increases in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, which were accompanied by alleviated liver injuries and reduced production of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). HRP was also found to reduce malondialdehyde (MDA) content and to restore superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities. Furthermore, HRP supplementation dose-dependently inhibited the expression of Toll-like receptor 4 (TLR4), phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated c-Jun N-terminal kinase (p-JNK), and phosphorylated mitogen activated protein kinase 38 (p-p38 MAPK) in the liver of LPS/d-GalN challenged mice. Pretreatment with HRP also inhibited LPS/d-GalN-induced activation and translocation of nuclear factor-κB (NF-κB). This study indicates that pretreatment with HRP protects against LPS/d-GalN-induced liver injury in mice via suppressing the TLR4-NF-κB signaling pathway. Sea buckthorn may be a hopeful drug for prevention of acute live injury.

Liu H ，Zhang W ，Dong S ，Song L ，Zhao S ，Wu C ，Wang X ，Liu F ，Xie J ，Wang J ，Wang Y ... -  《-》