Verbascoside ameliorates liver injury by suppressing Tnfrsf1a-induced oxidative stress

Liver injury remains a global health challenge; therefore, effective treatment strategies are required. As a phenylethanol glycoside compound, verbascoside (VB) possesses hepatoprotective activity; however, its mechanism of action is still unclear. In this research, we found that VB could improve lipid accumulation in AML12 cells induced by oleic acid. In a mouse model of liver injury induced by methionine- and choline-deficient diet (MCDD) and carbon tetrachloride (CCl₄), VB can reduce serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and improve the morphology and structure of liver cells. In the MCDD-induced injury model, VB decreased the proportion of CD11b⁺ in the liver of mice with liver injury. In CCl₄-induced injury models, VB reduced the proportion of the F4/80⁺ cell population. Transcriptome analysis of mouse liver showed that tumour necrosis factor (TNF) and IL-17 pathways were the main pathways via which VB exerts liver protection. Furthermore, based on the analysis results of transcriptome, the RAW264.7 cell injury model induced by lipopolysaccharide (LPS) verified VB could decreased the protein expression levels of Tnfrsf1a and correspondingly changed the protein levels of IL-17RA, ERK and p-ERK, key downstream targets of the IL-17 pathway. Taken together, VB administrated liver protection effect in Tnfrsf1a gene silencing group was more significant.