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

## TL;DR

This study shows that a polypeptide from Volvariella volvacea mushrooms helps protect the liver from alcohol damage by regulating stress and metabolism.

## Contribution

The study reveals a dual mechanism of a mushroom polypeptide in targeting both gene and metabolic pathways during alcohol detoxification.

## Key findings

- VVFP regulates 36 endoplasmic reticulum stress genes through protein processing pathways.
- VVFP modulates 23 hepatic metabolites, including phosphatidylcholines and organic acids.
- Eight coregulated genes interact with key metabolites via linoleic acid metabolism.

## Abstract

This study investigated the hepatoprotective mechanisms of Volvariella volvacea 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 (p < 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., ERP57, Derl) 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 (Got1, Arg2, Srm, 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.