Volvariella volvacea Polypeptide Mitigates Alcohol-Induced Liver Injury: A Multi-Omics Study

This study investigated the hepatoprotective mechanisms of <i>Volvariella volvacea</i> fruiting body polypeptide (VVFP, 1-3 kDa) against acute alcohol-induced liver injury using multi-omics approaches. Male ICR mice pretreated with VVFP (100-400 mg/kg) showed significantly prolonged alcohol tolerance latency (<i>p</i> < 0.05) and accelerated sobriety recovery compared to controls. Integrated transcriptomics and metabolomics revealed VVFP's dual regulatory effects: (1) transcriptional regulation of 36 endoplasmic reticulum stress genes (e.g., <i>ERP57</i>, <i>Derl</i>) through protein processing pathways (KEGG:04141), and (2) metabolic modulation of 23 hepatic metabolites, particularly phosphatidylcholines and organic acids, via amino acid biosynthesis and glycerophospholipid metabolism. Cross-omics analysis identified eight coregulated genes (<i>Got1</i>, <i>Arg2</i>, <i>Srm</i>, etc.) interacting with key metabolites (4-guanidinobutyric acid, GABA) through linoleic acid metabolism. These findings demonstrate VVFP's therapeutic potential as a functional food ingredient by highlighting its ability to simultaneously target hepatic stress responses and metabolic homeostasis during alcohol detoxification.