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

Abstract

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.

Melatonin protects H9c2 cells against ischemia/reperfusion‑induced apoptosis and oxidative stress via activation of the Nrf2 signaling pathway

“…Compared with in the SIR group, pretreatment with melatonin significantly increased the nuclear and whole cell expression levels of Nrf2. In addition, the present study analyzed the expression levels of HO-1, an important target gene of Nrf2 (24). Consistent with that of Nrf2, the expression levels of HO-1 were significantly increased when subjected to SIR, which further increased in response to pretreatment with melatonin.…”

Oxymatrine inhibits the pyroptosis in rat insulinoma cells by affecting nuclear factor kappa B and nuclear factor (erythroid-derived 2)-like 2 protein/heme oxygenase-1 pathways

“…The NF-κB pathway is suppressed by oxymatrine in colon cancer cells and fibroblast-like synoviocytes [ 39 , 40 ]. By increasing the levels of Nrf2 and HO-1, oxymatrine reduces renal ischemia-reperfusion injury, cerebral ischemia-reperfusion injury, arsenic trioxide (As 2 O 3 )-affected liver injury, and lipopolysaccharide/D-galactosamine-induced acute liver failure [ 41 - 44 ]. Therefore, to explore the mechanism of oxymatrine-inhibited pyroptosis in INS-1 cells, we analyzed the effects of oxymatrine on these factors.…”

Effects of wogonoside on the inflammatory response and oxidative stress in mice with nonalcoholic fatty liver disease

“…In the case of oxidative stress, Nrf2 dissociates from Keap1, and Nrf2 translocates into the nucleus to bind to antioxidant response element (ARE) to activate the expression of HO-1, an antioxidant gene, thus enhancing the antioxidant capacity of cells (Fan et al 2017). The increase of Nrf2 and HO-1 protein expression can enhance the antioxidant capacity of the body and protect the body from the damage of reactive oxygen species (Xu et al 2018). A number of studies have confirmed that in NAFLD model, the regulation of Nrf2 pathway activation is an important mechanism to play the role of liver protection (Feng et al 2017;Yan et al 2018).…”