3,4-hydroxyphenyl lactic acid fromLactiplantibacillus plantarumprevents alcoholic liver injury in mice

Alcoholic liver disease (ALD) is a major health burden linked to oxidative stress, gut dysbiosis, and disrupted hepatic metabolism. While Lactiplantibacillus plantarum ( L. plantarum ) has shown potential in alleviating ALD, the specific mechanisms and bioactive components remain unclear. This study investigated the hepatoprotective effects of L. plantarum fermentation liquid (PFL) and its key metabolite, 3,4-hydroxyphenyl lactic acid (HPLA), against alcohol-induced liver injury. Using acute and chronic alcohol intoxication mouse models, we demonstrated that PFL significantly reduced mortality, attenuated hepatocyte damage, and restored alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities. UHPLC-QTOF-MS/MS analysis identified HPLA as the primary active component in PFL, exhibiting potent antioxidant properties. In vitro and in vivo experiments revealed that HPLA mitigated oxidative stress by enhancing superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, reducing malondialdehyde (MDA) levels, and suppressing lipid accumulation. Mechanistically, network pharmacology and molecular validation highlighted that HPLA alleviated hepatic injury by modulating the EGFR/PPAR-α signaling axis, thereby counteracting alcohol-induced oxidative stress and lipid metabolism disorders. These findings elucidate a novel "gut-liver" axis mechanism mediated by HPLA, offering a theoretical foundation for the clinical application of L. plantarum and its metabolites in ALD management.