Protective effects of oxymatrine against lipopolysaccharide/D-galactosamine-induced acute liver failure through oxidative damage, via activation of Nrf2/HO-1 and modulation of inflammatory TLR4-signaling pathways

Oxymatrine has a variety of pharmacological functions, including anti-viral, anti-liver fibrotic, anti-cancer, anti-bacterial, anti-epidemic, analgesic, anti-allergy and anti-inflammatory properties. The present study aimed to investigate the protective effects of oxymatrine against lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute liver failure and the associated underlying mechanisms. Mice were administrated 4 mg/kg LPS and 600 mg/kg D-GalN. Then, mice in the Oxymatrine group were treated with 120 mg/kg of oxymatrine for 4 weeks. Oxymatrine treatment increased survival rate, decreased plasma aspartate transaminase and alanine aminotransferase activity, increased superoxide dismutase and glutathione peroxidase and decreased malondialdehyde, tumor necrosis factor- and myeloperoxidase activities in mice with LPS/D-GalN-induced liver failure. Furthermore, Oxymatrine activated nuclear factor erythroid 2-related factor (Nrf) 2 and heme oxygenase (HO)-1 protein expression, and suppressed Toll like receptor (TLR)4, myeloid differentiation primary response 88 and nuclear factor-B protein expression in mice LPS/D-GalN mice. Overall, the present study suggests that oxymatrine effectively attenuates LPS/D-GalN-induced acute liver failure by oxidative damage via activation of Nrf2/HO-1 and modulation of TLR4-dependent inflammatory signaling pathways.