# Characterization and screening of a novel octapeptide from protein hydrolysates of Crassostrea gigas and its immunomodulatory effects on RAW264.7 cells

**Authors:** Gongming Wang, Chunna Jiao, Weijun Wang, Jianqiang Chen, Huawei Qin, Jian Zhang, Yingjiang Xu, Yunping Zhao, Hui Huang, Yuexin Jing

PMC · DOI: 10.1016/j.fochx.2026.103684 · Food Chemistry: X · 2026-02-18

## TL;DR

A new oyster-derived peptide was identified that can both stimulate and regulate immune responses, making it useful for functional foods.

## Contribution

A novel immunomodulatory octapeptide (SWDNFLQR) from oyster protein was discovered and shown to regulate immune pathways.

## Key findings

- SWDNFLQR activates TLR and PI3K-Akt pathways to enhance immune cell activity.
- Higher concentrations of SWDNFLQR inhibit NF-κB, reducing excessive inflammation.
- The peptide promotes immune cell proliferation, phagocytosis, and cytokine secretion.

## Abstract

Food-derived bioactive peptides show great potential for functional foods, given their structural adaptability and safety. Crassostrea gigas contains abundant bioactive proteins, but the immunomodulatory mechanism of their peptides remains unclear. In this research, 29 new peptides were identified from papain-hydrolyzed oyster extracts using LC-MS/MS, and target peptide SWDNFLQR with high activity potential was obtained through bioinformatics screening and chemically synthesized. The immunomodulatory properties of SWDNFLQR were assessed through the RAW264.7 cells model and iTRAQ quantitative proteomics. SWDNFLQR enhanced proliferation, phagocytosis, and secretion of NO, TNF-α, and IL-6. It activates Toll-like receptors and the PI3K-Akt signaling pathway, modulating key proteins Fn1 and Prkacb. Notably, higher concentrations of SWDNFLQR specifically inhibited NF-κB pathway activation, indicating its dual immunomodulatory role in stimulating immune responses and mitigating excessive inflammation. This positions SWDNFLQR as a valuable component for the formulation of anti-inflammatory and immune-regulating functional foods.

•A new type of oyster peptide (SWDNFLQR) with immunomodulatory activity was identified and screened out.•Bidirectional immune regulation‌ achieved by activating TLR/PI3K-Akt while inhibiting NF-κB pathways.•Integrative approach combining LC-MS/MS, bioinformatics screening, synthetic chemistry, and proteomics.

A new type of oyster peptide (SWDNFLQR) with immunomodulatory activity was identified and screened out.

Bidirectional immune regulation‌ achieved by activating TLR/PI3K-Akt while inhibiting NF-κB pathways.

Integrative approach combining LC-MS/MS, bioinformatics screening, synthetic chemistry, and proteomics.

## Linked entities

- **Proteins:** FN1 (fibronectin 1), PRKACB (protein kinase cAMP-activated catalytic subunit beta)
- **Chemicals:** NO (PubChem CID 24822), IL-6 (PubChem CID 165368475)

## Full-text entities

- **Genes:** Mapk14 (mitogen-activated protein kinase 14) [NCBI Gene 26416] {aka CSBP2, Crk1, Csbp1, Mxi2, PRKM14, PRKM15}, 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}, Ccl4 (C-C motif chemokine ligand 4) [NCBI Gene 20303] {aka AT744.1, Act-2, MIP-1B, Mip1b, Scya4}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Ccl5 (C-C motif chemokine ligand 5) [NCBI Gene 20304] {aka MuRantes, RANTES, SISd, Scya5, TCP228}, Ccr5 (C-C motif chemokine receptor 5) [NCBI Gene 12774] {aka AM4-7, CD195, Cmkbr5}, Casp3 (caspase 3) [NCBI Gene 12367] {aka A830040C14Rik, AC-3, CASP-3, CC3, CPP-32, CPP32}, Il17a (interleukin 17A) [NCBI Gene 16171] {aka Ctla-8, Ctla8, IL-17, IL-17A, Il17}, Smad3 (SMAD family member 3) [NCBI Gene 17127] {aka Madh3}, Tlr4 (toll-like receptor 4) [NCBI Gene 21898] {aka Lps, Ly87, Ran/M1, Rasl2-8}, Ccnd1 (cyclin D1) [NCBI Gene 12443] {aka CycD1, Cyl-1, PRAD1, bcl-1, cD1}, Tgfbr1 (transforming growth factor, beta receptor I) [NCBI Gene 21812] {aka ALK5, Alk-5, ESK2, TGFR-1, TbetaR-I, TbetaRI}, Mapk3 (mitogen-activated protein kinase 3) [NCBI Gene 26417] {aka Erk-1, Erk1, Ert2, Esrk1, Mnk1, Mtap2k}, Mtor (mechanistic target of rapamycin kinase) [NCBI Gene 56717] {aka 2610315D21Rik, FRAP, FRAP2, Frap1, RAFT1, RAPT1}, Prkacb (protein kinase, cAMP dependent, catalytic, beta) [NCBI Gene 18749] {aka CbPKA, PKA C-beta, Pkacb}, Thbs1 (thrombospondin 1) [NCBI Gene 21825] {aka TSP-1, TSP1, Thbs-1, tbsp1}, Fn1 (fibronectin 1) [NCBI Gene 14268] {aka E330027I09, Fn, Fn-1}, Cdk4 (cyclin dependent kinase 4) [NCBI Gene 12567] {aka Crk3}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, Ccr1 (C-C motif chemokine receptor 1) [NCBI Gene 12768] {aka Cmkbr1, Mip-1a-R}, Nfkbia (nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha) [NCBI Gene 18035] {aka Nfkbi}, Myd88 (myeloid differentiation primary response gene 88) [NCBI Gene 17874], Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 18708] {aka PI3K, p50alpha, p55alpha, p85alpha}, TNF (tumor necrosis factor) [NCBI Gene 280943] {aka TNF-a, TNF-alpha, TNFa}, TLR4 (toll like receptor 4) [NCBI Gene 281536], Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Il1 (interleukin 1 complex) [NCBI Gene 111343] {aka Il-1}, Cdk1 (cyclin dependent kinase 1) [NCBI Gene 12534] {aka Cdc2, Cdc2a, p34<CDC2>}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 21803] {aka TGF-beta1, TGFbeta1, Tgfb, Tgfb-1}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Nup42 (nucleoporin 42) [NCBI Gene 231042] {aka CG1, NLP-1, Nlp1, Nupl2}, Camp (cathelicidin antimicrobial peptide) [NCBI Gene 12796] {aka CAP18, CLP, Cnlp, Cramp, FALL39, MCLP}, Tlr2 (toll-like receptor 2) [NCBI Gene 24088] {aka Ly105}, Traf3 (TNF receptor-associated factor 3) [NCBI Gene 22031] {aka CAP-1, CD40bp, CRAF1, LAP1, T-BAM, TRAFAMN}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, Gss (glutathione synthetase) [NCBI Gene 14854] {aka GS-A/GS-B, GSH-S}, Nos2 (nitric oxide synthase 2, inducible) [NCBI Gene 18126] {aka MAC-NOS, NOS-II, Nos-2, Nos2a, i-NOS, iNOS}, Trp53 (transformation related protein 53) [NCBI Gene 22059] {aka Tp53, bbl, bfy, bhy, p44, p53}, Il4 (interleukin 4) [NCBI Gene 16189] {aka BSF-1, Il-4}, Tlr6 (toll-like receptor 6) [NCBI Gene 21899], Serpinb8 (serine (or cysteine) peptidase inhibitor, clade B, member 8) [NCBI Gene 20725] {aka CAP-2, CAP2, NK10, Spi8, ovalbumin}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, IL10 (interleukin 10) [NCBI Gene 281246] {aka IF2A}, Cd40 (CD40 antigen) [NCBI Gene 21939] {aka Bp50, GP39, HIGM1, IGM, IMD3, T-BAM}
- **Diseases:** chronic inflammation (MESH:D007249), cancer (MESH:D009369), osteoporotic (MESH:D058866), atherosclerosis (MESH:D050197), infections (MESH:D007239), toxicity (MESH:D064420), lymphoma (MESH:D008223)
- **Chemicals:** Pro (MESH:D011392), NaCl (MESH:D012965), formic acid (MESH:C030544), streptomycin (MESH:D013307), polyacrylamide (MESH:C016679), acetonitrile (MESH:C032159), Leu (MESH:D007930), CCK-8 (MESH:D012844), water (MESH:D014867), neutral red (MESH:D009499), Peptide (MESH:D010455), SDS (MESH:D012967), Gly (MESH:D005998), Infliximab (MESH:D000069285), NO (MESH:D009569), NO (MESH:D009614), AGPAGPMGPN (-), penicillin (MESH:D010406), disulfide (MESH:D004220), CG2 (MESH:C572619), urea (MESH:D014508), amino acids (MESH:D000596), Asp (MESH:D001224), Arg (MESH:D001120), TFA (MESH:D014269), Ser (MESH:D012694), Phe (MESH:D010649), glutathione (MESH:D005978), CO2 (MESH:D002245), ATP (MESH:D000255), LPS (MESH:D008070), cysteine (MESH:D003545), lipid (MESH:D008055), PVDF (MESH:C024865), Trp (MESH:D014364), KCl (MESH:D011189), PBS (MESH:D007854), Thr (MESH:D013912), ROS (MESH:D017382), glucose (MESH:D005947)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Mytilus edulis (blue mussel, species) [taxon 6550], Ostreidae (oysters, family) [taxon 6563], Magallana gigas (Pacific oyster, species) [taxon 29159]
- **Cell lines:** RAW 264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493)

## Full text

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## Figures

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## References

40 references — full list in the complete paper: https://tomesphere.com/paper/PMC12963996/full.md

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Source: https://tomesphere.com/paper/PMC12963996