Chrysanthemum 3,5-O-dicaffeoylquinic acid ameliorates mouse alcoholic liver injury by suppressing the TLR-4/NF-κB pathway and restoring glycerophospholipid homeostasis.

3,5-O-Dicaffeoylquinic acid (3,5-DCQA) from edible Gongju chrysanthemum has shown protective effects against alcoholic hepatocyte injury in our previous study. However, the specific effects and mechanisms of 3,5-DCQA in a mouse model of liver injury remain underexplored. This study aimed to examine the efficacy and primary mechanism of 3,5-DCQA from Gongju chrysanthemum in ameliorating acute alcoholic liver injury in mice. The results indicated that 3,5-DCQA effectively attenuated inflammation and apoptosis by regulating the content of key factors (e.g. MyD88, NF-κB) in the TLR-4/NF-κB pathway, contributing to its protective role against alcohol-induced liver injury. 3,5-DCQA also inhibited inflammation and apoptosis by recovering the key metabolites (e.g. phosphatidylserine) and related genes (e.g. Lpgat1) of glycerophospholipid metabolism. These results were further verified by transcriptomic and metabolomic analyses, showing that 3,5-DCQA exerts protective effects against alcohol-induced liver injury by modulating glycerophospholipid metabolism and suppressing oxidative stress, inflammation, and apoptosis through the TLR-4/NF-κB pathway. The current findings highlight the hepatoprotectivity of 3,5-DCQA and may facilitate the application of Gongju chrysanthemum in liver-protective functional foods.