Improvement Effect and Mechanism of Angelica keiskei Enzyme on Alcoholic Liver Injury in Mice

This study investigated the hepatoprotective effects and mechanisms of fermented Angelica keiskei (FAK), produced through synergistic fermentation using Lactobacillus plantarum and Saccharomyces cerevisiae, against alcohol-induced liver injury in mice. Male Kunming mice were randomly divided into seven groups (n=12 per group): normal control, model control, silibinin-treated, freeze-dried Angelica keiskei powder, and low-, medium-, and high-dose FAK groups. Alcohol-induced liver injury was established via 30-days intragastric administration of edible alcohol, with body weight monitored periodically. Post-intervention assessments included serum lipid profiles, organ indices, hepatic injury markers, antioxidant enzymes, inflammatory cytokines, and gut microbiota alterations. Results demonstrated that FAK significantly attenuated alcohol-induced weight loss (P<0.05) and reduced hepatic index, serum lipid levels, and hepatic injury markers. FAK intervention notably decreased hepatic lipid accumulation while enhancing antioxidant capacity, as evidenced by increased glutathione peroxidase (GSH-Px) activity and reduced malondialdehyde (MDA) concentrations (P<0.05), and could alleviate alcohol metabolism-induced hepatic oxidative damage. Mechanistic analyses revealed that FAK restored the Firmicutes-Bacteroidetes (F/B) ratio to near-normal levels and ameliorated alcohol-induced phylum- and genus-level dysbiosis, and the abundance of beneficial bacteria, such as Muribaculaceae, increased. This alleviated the abnormal changes in community relative abundance at the phylum and genus levels by strengthening the gut barrier, which was achieved by reducing LPS translocation and promoting SCFA production (e.g., Muribaculaceae could produce SCFAs), thereby reducing the production and release of endotoxins. In this study, FAK primarily exerted its effects by modulating the structure of the gut microbiota, reflecting the unique concept of "using bacteria to combat bacterial imbalance". It was speculated that FAK might repair the intestinal barrier and maintain intestinal homeostasis in mice with alcoholic liver injury by altering the diversity and community structure of the gut microbiota. This study provides a theoretical foundation for the high-value utilization of Angelica keiskei resources and its potential application in functional foods targeting alcohol-related hepatic disorders.