# Screening and identification of novel anti-inflammatory peptides from sea cucumber gonads: In silico and in vitro analysis

**Authors:** Zhiqin Zhang, Yongke Deng, Jingxuan Wang, Peipei Dou, Hongbing Fan, Xiangquan Zeng, Xinguang Fan, Haimei Liu, Qin Zhao

PMC · DOI: 10.1016/j.fochx.2026.103510 · Food Chemistry: X · 2026-01-16

## TL;DR

Researchers found three new anti-inflammatory peptides from sea cucumber gonads that are safe and effective at reducing inflammation in lab tests.

## Contribution

The study introduces a novel screening strategy for marine-derived anti-inflammatory peptides and identifies three new candidates with strong activity.

## Key findings

- The peptides showed no cytotoxicity and promoted macrophage cell proliferation at tested concentrations.
- They significantly reduced nitric oxide and pro-inflammatory cytokines in an LPS-induced inflammation model.
- Molecular docking showed strong binding to Toll-like receptors via hydrogen bonds and hydrophobic interactions.

## Abstract

This study identified three novel anti-inflammatory peptides from sea cucumber gonad hydrolysates: GDRGF, FDGPEGPRGPPGSEGRQG, and PSNLGTGLR. In vitro experiments demonstrated that these peptides, at concentrations ranging from 25 to 400 μg/mL, exhibited no cytotoxicity toward RAW264.7 macrophages and significantly promoted cell proliferation (P < 0.05). In an lipopolysaccharide (LPS)-induced inflammation model, all three peptides markedly suppressed the secretion of nitric oxide (NO) and pro-inflammatory cytokines (P < 0.05), with GDRGF exhibiting the highest NO inhibition rate of 62.89%. Molecular docking results confirmed that the three peptides interact with Toll-like receptors 2 and 4 receptors via hydrogen bonding and hydrophobic interactions. Analysis of key residues suggested that internal or C-terminal arginine (R) may enhance anti-inflammatory activity by inhibiting NO production and blocking LPS signaling pathways. This study provides an efficient screening strategy for marine-derived anti-inflammatory peptides and lays a theoretical foundation for developing anti-inflammatory functional foods from sea cucumber gonads.

•Three anti-inflammatory sea cucumber gonad peptides were noncytotoxic and promoted RAW264.7 proliferation at 25-400 μg/mL.•They significantly inhibited LPS-induced NO and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6).•Molecular docking revealed high-affinity binding (≤ −7.0 kcal/mol) via hydrogen bonds and hydrophobic interactions.•Internal and C-terminal arginine residues may block LPS signaling and suppress NO production.

Three anti-inflammatory sea cucumber gonad peptides were noncytotoxic and promoted RAW264.7 proliferation at 25-400 μg/mL.

They significantly inhibited LPS-induced NO and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6).

Molecular docking revealed high-affinity binding (≤ −7.0 kcal/mol) via hydrogen bonds and hydrophobic interactions.

Internal and C-terminal arginine residues may block LPS signaling and suppress NO production.

## Linked entities

- **Chemicals:** nitric oxide (PubChem CID 145068), IL-6 (PubChem CID 165368475)

## Full-text entities

- **Diseases:** cytotoxicity (MESH:D064420), inflammation (MESH:D007249), inflammatory cytokines (MESH:D000080424)
- **Chemicals:** NO (MESH:D009569), LPS (MESH:D008070)
- **Species:** Cucumis sativus (cucumber, species) [taxon 3659]

## Full text

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## Figures

11 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12861254/full.md

## References

90 references — full list in the complete paper: https://tomesphere.com/paper/PMC12861254/full.md

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Source: https://tomesphere.com/paper/PMC12861254