# Gastric-protective and antioxidant effects of fermented Pichia pastoris residue hydrolyzed peptides on alcohol-treated mice

**Authors:** Yang Zhou, Yuxiang Huang, Shuaijun Guo, Chensi Wu, Xinru Shao, Chenlu Liu, Xinting Cui, Li Li, Hao Zang, Guangqing Xia

PMC · DOI: 10.1515/biol-2025-1257 · Open Life Sciences · 2026-02-12

## TL;DR

This study shows that peptides from fermented Pichia pastoris residue protect mice from alcohol-induced stomach ulcers by reducing oxidative stress and inflammation.

## Contribution

The novel contribution is the identification of PPRHP as a gastroprotective and antioxidant agent with potential for nutritional intervention.

## Key findings

- PPRHP reduced ulcer area, edema, and leukocyte infiltration in a dose-dependent manner in mice.
- PPRHP reversed oxidative stress by increasing antioxidant enzyme levels and decreasing lipid peroxidation markers.
- The most effective dose of PPRHP was 400 mg/kg, showing the strongest protective effects.

## Abstract

Alcoholic gastric ulcer is a prevalent digestive disorder closely associated with oxidative stress and inflammatory damage, prompting growing interest in bioactive peptides as potential nutritional interventions. This study aimed to evaluate the nutritional composition, in vitro antioxidant activity, and gastroprotective effects of Pichia pastoris residue hydrolyzed peptides (PPRHP) in a mouse model of ethanol-induced gastric injury. Amino acid analysis revealed that PPRHP contains 17 amino acids with an essential-to-total amino acid ratio of 0.512. In vitro assays demonstrated strong radical (ABTS and hydroxyl) and hydrogen peroxide scavenging abilities, as well as copper ion chelation capacity, attributable to the reactive residues within the peptide sequences like histidine, tyrosine, and methionine. In vivo, pretreatment with PPRHP (200, 400, and 800 mg/kg) dose-dependently ameliorated ethanol-induced gastric damage, as evidenced by reduced ulcer area, submucosal edema, and leukocyte infiltration. Furthermore, PPRHP significantly reversed oxidative stress by elevating gastric superoxide dismutase and serum catalase levels while reducing gastric malondialdehyde and myeloperoxidase levels (p < 0.001), with the most pronounced effects observed at the medium dose of 400 mg/kg. These findings indicate that PPRHP, a peptide-rich and antioxidant substance, exerts significant protective effects against ethanol-induced gastric ulcers, likely through mechanisms involving free radical scavenging, metal ion chelation, inhibition of lipid peroxidation, and restoration of oxidative-antioxidative balance.

## Linked entities

- **Chemicals:** ethanol (PubChem CID 702), hydrogen peroxide (PubChem CID 784), malondialdehyde (PubChem CID 10964)
- **Diseases:** gastric ulcer (MONDO:0001126)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** CAT (catalase) [NCBI Gene 847], MPO (myeloperoxidase) [NCBI Gene 4353], Alb (albumin) [NCBI Gene 11657] {aka Alb-1, Alb1, BCL001, BCL002, BPL001}, SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, Mpo (myeloperoxidase) [NCBI Gene 17523] {aka mKIAA4033}, Tlr4 (toll-like receptor 4) [NCBI Gene 21898] {aka Lps, Ly87, Ran/M1, Rasl2-8}, Blnk (B cell linker) [NCBI Gene 17060] {aka BASH, Bca, Ly-57, Ly57, Lyw-57, SLP-65}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Nfe2l2 (nuclear factor, erythroid derived 2, like 2) [NCBI Gene 18024] {aka Nrf2}, Cat (catalase) [NCBI Gene 12359] {aka 2210418N07, Cas-1, Cas1, Cs-1}, Myd88 (myeloid differentiation primary response gene 88) [NCBI Gene 17874]
- **Diseases:** digestive disorder (MESH:D004066), ulcer (MESH:D014456), toxicity (MESH:D064420), erosion (MESH:D014077), necrosis (MESH:D009336), dislocation (MESH:D004204), mucosal damage (MESH:D052016), PPRHP (MESH:D018365), gastric (MESH:D013272), atrophy (MESH:D001284), edema (MESH:D004487), inflammation (MESH:D007249), Alcoholic gastric ulcer (MESH:D013276), Helicobacter pylori infection (MESH:D016481), bleeding (MESH:D006470)
- **Chemicals:** indomethacin (MESH:D007213), omeprazole (MESH:D009853), amino acid (MESH:D000596), phosphoric acid (MESH:C030242), aspartic acid (MESH:D001224), MDA (MESH:D008315), bicarbonate (MESH:D001639), potassium persulfate (MESH:C009007), sulfur (MESH:D013455), H2O2 (MESH:D006861), O2 - (MESH:D013481), 2,2'-Azino-Bis(3-Ethylbenzothiazoline-6-Sulfonicacid) Diammonium Salt (-), hematoxylin (MESH:D006416), CuSO4 (MESH:D019327), unsaturated fatty acids (MESH:D005231), sodium citrate (MESH:D000077559), H+ (MESH:D006859), Alcohol (MESH:D000438), eosin (MESH:D004801), acetate (MESH:D000085), sodium acetate (MESH:D019346), ROS (MESH:D017382), ninhydrin (MESH:D009555), glutamine (MESH:D005973), carboxymethylcellulose sodium (MESH:D002266), ABTS (MESH:C002502), paraformaldehyde (MESH:C003043), cysteine (MESH:D003545), lipid (MESH:D008055), nitrogen (MESH:D009584), polysaccharides (MESH:D011134), xylene (MESH:D014992), pentobarbital sodium (MESH:D010424), ferrous sulfate heptahydrate (MESH:C020748), hypochlorous acid (MESH:D006997), Coomassie Brilliant Blue G-250 (MESH:C004692), 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (MESH:C010643), saline (MESH:D012965), paraffin (MESH:D010232), pyrocatechol violet (MESH:C009134), metal (MESH:D008670), Gallic acid (MESH:D005707), salicylic acid (MESH:D020156), acid (MESH:D000143), glutamic acid (MESH:D018698), HCl (MESH:D006851), acetic acid (MESH:D019342), copper (MESH:D003300), EAAs (MESH:D000601), hydroxyl (MESH:D017665), asparagine (MESH:D001216), 4-aminoantipyrine (MESH:D000675), Ethanol (MESH:D000431), carotenoids (MESH:D002338), water (MESH:D014867), phenol (MESH:D019800), lithium citrate (MESH:C070669), peptides (MESH:D010455)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Komagataella pastoris (species) [taxon 4922]

## Full text

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## Figures

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## References

42 references — full list in the complete paper: https://tomesphere.com/paper/PMC12917558/full.md

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Source: https://tomesphere.com/paper/PMC12917558