Protective effect of caffeic acid tetramer based on PI3K/AKT and MAPK/NF-κB signaling pathway on acute liver injury...

Arnebia euchroma (Royle) Johnstn (AE) is a traditional Chinese medicine primarily produced in Xinjiang and Inner Mongolia, and it derives its medicinal attributes from the desiccated roots of AE species. Caffeic acid tetramer (CATE), the main phenolic acid monomer isolated from the aqueous extract of AE, was investigated for its liver-protecting effects and anti-inflammatory mechanisms in this study. Acute liver injury (ALI) models were established in murine using lipopolysaccharide (LPS)/d-galactosamine (D-GalN) to elucidate the effects of CATE. Prolonged pretreatment with CATE for 14 days notably decreased serum levels of inflammatory markers in ALI murine models, suggesting a significant improvement in hepatic inflammation. Moreover, reduced expression of IL-6, TNF-α, PI3K, P-Akt, P-Erk1/2, and P-P65 proteins was observed in liver tissues from the CATE pretreatment group compared to the ALI group, aligning with findings from an in vitro inflammation model. These results demonstrate the hepatoprotective and anti-inflammatory properties of CATE, which are attributed to its ability to suppress inflammatory factors and inhibit activation of the PI3K/Akt and MAPK/NF-κB pathways. This study provides a strong rationale for the therapeutic application of CATE in ameliorating ALI and establishes a foundation for its clinical exploration and development.