A pectic polysaccharide from wax gourd peel improves ethanol-induced gastric ulcer injury in mice via the PI3K/AKT signaling pathway.

The pectic polysaccharide WGPP-1a (46.8 kDa) has been obtained from wax gourd peel (WGP) which is a popular soup ingredient and Chinese herbal medicines in China. Monosaccharide composition, methylation analysis, FT-IR and NMR demonstrate that WGPP-1a is composed of rhamnogalacturonan I (RG-I) and homogalacturonan (HG) domains with mass ratios of 4:1. The RG-I domains contain a highly branched structure that is substituted primarily with β-D-1,4-galactan, α-L-1,5-arabinan and β-D-1,4-glucan. In ethanol-induced gastric ulcer mice, WGPP-1a reduced ulcer area, restored mucosal glycoproteins. In vitro, WGPP-1a enhanced GES-1 cell viability and reduced apoptosis. Untargeted LC-MS metabolomics of murine gastric tissues revealed 322 differential metabolites (163 upregulated, 159 downregulated) between Model and control groups, with WGPP-1a treatment restoring 120 metabolites (53 upregulated, 67 downregulated). PCA and OPLS-DA demonstrated WGPP-1a's reversal of ethanol-induced perturbations. KEGG pathway enrichment identified eight core pathways modulated by WGPP-1a, including PI3K/AKT signaling, Linoleic acid metabolism, and mTOR/FoxO pathways. Notably, Mechanistically, WGPP-1a activated the PI3K/AKT pathway, elevating Bcl-2/Bax ratios and suppressing the expression levels of pro-apoptotic proteins Bax and Caspase3. These results suggest that WGPP-1a may be an effective agent for protecting against alcoholic gastric ulcers and provides a new perspective for the resource utilization of WGP.