zhao, w. | bioRxiv Science

bioRxiv2025

3,4-hydroxyphenyl lactic acid from Lactiplantibacillus plantarum prevents 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- 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. ImportanceNumerous animal studies and clinical trials have demonstrated the effectiveness of probiotics in treating alcoholic liver disease. In this study, we primarily created a mouse model for both acute and chronic alcoholism and discovered that Lactiplantibacillus plantarum fermentation solution significantly decreased the inflammatory response and oxidative stress caused by alcohol. Its key metabolite, 3,4-hydroxyphenyl lactic acid (HPLA), exhibited strong antioxidant properties, helping to reduce oxidative stress by preventing lipid accumulation. This research offers insights into how probiotic interventions can mitigate alcoholic liver damage, enhancing our understanding of the protective effects of Lactiplantibacillus plantarum and emphasizing the potential of its metabolite, HPLA, as a targeted treatment for alcoholic liver disease.

microbiology↗

bioRxiv2018

Host protein CD63 enhances viral RNA replication by interacting with human astrovirus nonstructural protein nsP1a/4

Human astrovirus nonstructural protein nsP1a/4, located at the C-terminal end of nsP1a, is thought to be involved in the regulation of RNA replication and capsid maturation;however, its rolesviral growth and virulence are not well understood. We investigated the intracellular host proteins that interact with nsP1a and explored the potential roles of the interaction in the pathogenesis of human astrovirus infection. We screened 14 independent proteins with a cDNA library derived from Caco-2 cells using a yeast two-hybrid technique. Deletion analysis revealed that interaction between the nsP1a/4 domain and the large extracellular loop (LEL) domain of the human protein CD63 is necessary for astrovirus replication. The interaction was confirmed by glutathione-S-transferase (GST) pull-down assays and co-immunoprecipitation assays. Confocal microscopy showed that nsP1a/4 and CD63 co-localized in the cytoplasm of infected cells. Over expression of CD63 promoted viral RNA synthesis, whereas knockdown of CD63 markedly decreased viral RNA levels. Those results suggest that CD63 plays a critical role in human astrovirus RNA replication. The interaction between CD63 and nsP1a/4 provides a channel to further understand the roles of interactions between host and virus proteins in astrovirus infection and release.\n\nIMPORTANCEHuman astroviruses cause gastroenteritis in young children and immunocompromised patients. In this study, we provide evidence that nsP1a/4, a nonstructural protein located at the C-terminal end of the human astrovirus nsP1a polyprotein, interacts with the host protein CD63. Over expression of CD63 promoted viral RNA replication, whereas knockdown of CD63 decreased virus RNA replication, indicating that CD63 plays a critical role in the human astrovirus life cycle.

microbiology↗