Protective Effect Of Tectorigenin On LPS/D-GalN Induced Acute Liver Failure In Mice

Background&Aims:Tectorigenin,a component of Belamcanda Adans,has received attention due to its antiproliferation,anti-inflammatory,and antioxidant activities.In this study,we investigated the effects of Tectorigenin on LPS/D-GalN-induced fulminant hepatic failure in mice and LPS-stimulated macrophages(RAW 264.7 cells).Methods:Acute liver failure was induced by the intraperitoneal injection of 50?g/kg LPS and 800 mg/kg D-GalN.Mice were divided into control group,LPS model,and Tectorigenin treatment group.For Tectorigenin treatment group,different concentrations of Tectorigenin(12.5 mg/kg,25 mg/kg and 50 mg/kg)were injected intraperitoneally 30 min before LPS/D-GalN administration.The RAW 264.7 cell treated with LPS(100 ng/mL)was used as vitro model.The RAW 264.7 cell line was divided into control group,LPS model,and different concentrations of Tectorigenin treatment group.Liver pathological changes,apoptosis and mortality in mice was observed.Western blot was used to detect the protein level of NF-?B pathway and MAPK pathway,and the expression levels of autophagy-reated proteins LC3 ?,LC3 ? and P62.qRT-PCR was used to detect the mRNA levels of IL-6 and TNF-? in liver tissue and RAW 264.7 cell.ELISA kit was used to detect in the cytokine levels of IL-6 and TNF-? in the serum and cell supernatant.Transmission electron microscopy was used to observe autophagosomes in liver tissue.Results:Pretreatment with Tectorigenin significantly reduced the serum levels of ALT and AST,histological injury,apoptosis,and the mortality of ALF mice,by suppressing the production of inflammatory cytokines such as TNF-? and IL-6.Tectorigenin also suppressed the activation of the inflammatory response in LPS-stimulated RAW 264.7 cells.Tectorigenin-induced protection is mediated through its mitigation of TLR4 expression,inhibition of MAPK and NF-?B pathway activation,and promotion of autophagy in ALF mice and LPS-stimulated RAW 264.7 cells.Conclusions:Tectorigenin has therapeutic potential for ALF in mice via the regulation of TLR4/MAPK and TLR4/NF-?B pathways and autophagy.