Buddleoside inhibits TLR4-related pathway in a mouse model of acute liver failure, promotes autophagy, and inhibits inflammation

Abstract

Purpose: To study the inhibitory influence of buddleoside on TLR4-associated pathway, autophagy and inflammation in a mouse model of acute liver failure (ALF).Methods: Sixty male C57BL/6 mice were assigned to 5 groups: control, model, and three dose-groups of buddleoside, with 12 mice per group. Levels of interleukin (IL)-1, IL-6, TLR4 pathway-associated proteins, and autophagy-related proteins in each group were determined; cell adhesion in each group was also analyzed.Results: Levels of TLR4, MAPK and NF-кB-related pathways in model mice were significantly upregulated, relative to control mice, but they were more down-regulated in the 3 anthocyanin groups than in model group (p < 0.05). There were significantly higher levels of TNF-α, IL- and IL-6 in model mice than in the control group, but they were down-regulated in high-, medium- and low-dose mice, relative to model mice. The population of adherent cells was significantly higher in ALF mice than in controls, butthere were markedly lower numbers of these cells in the 3 anthocyanin-treated mice than in model mice (p < 0.05).Conclusion: Buddleoside mitigates ALF in mice by down-regulating inflammatory factors, reducing serum levels of ALT and AST, and up-regulating autophagy-related protein expressions by activating TLR4/MAPK/NF-кB signaling pathway. Thus, buddleoside may be useful in the treatment of acute liver failure, but this has to be curtained through clinical trials.