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

3,5-<i>O</i>-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 (<i>e.g.</i> 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 (<i>e.g.</i> phosphatidylserine) and related genes (<i>e.g.</i> 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.