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‑κB 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.