# Unlocking the Antioxidant Potential of Sea Cucumber Viscera: Pre-Treatment Modulates the Keap1-Nrf2 Pathway and Gut Microbiota to Attenuate Cold Stress-Induced Oxidative Damage

**Authors:** Yang Gao, Xin Qiao, Xueyi Jing, Weiyue Li, Dongchao Zhang, Lei Pu, Jianbin Zhang, Hua Yang, Xingyao Pei, Liang Hong

PMC · DOI: 10.3390/antiox14111355 · 2025-11-13

## TL;DR

Sea cucumber viscera, a seafood byproduct, can reduce oxidative stress and liver damage by activating antioxidant pathways and improving gut microbiota.

## Contribution

This is the first study to repurpose sea cucumber viscera as a functional food with dual antioxidant and microbiota-modulating effects.

## Key findings

- SCV reduced oxidative damage by activating the Keap1-Nrf2/HO-1 pathway and lowering MDA levels in serum and liver.
- SCV improved liver histology by reducing vacuolization and inflammation.
- SCV increased beneficial gut bacteria like Bifidobacterium and Akkermansia, and enriched vitamin B12 synthesis pathways.

## Abstract

The internal organs of sea cucumbers (SCV) are a byproduct of the seafood processing industry and hold untapped potential as a functional food. This study investigates the antioxidant capacity of SCV and its regulatory effects on the gut microbiota in a mouse model of oxidative stress induced by chronic cold exposure. The results indicate that SCV possesses a rich nutritional composition, containing various components such as calcium, phosphorus, and polysaccharides, and exhibit strong scavenging activity against three types of free radicals in vitro: DPPH, OH−, and O2−. SCV significantly reduced MDA levels in both serum and liver, while activating the Keap1-Nrf2/HO-1 pathway, leading to a significant decrease in the expression of HSP70 and HSP90 genes and a marked increase in Nrf2 gene expression, thereby alleviating oxidative damage. Histological analysis revealed that SCV alleviated liver damage, reducing hepatocellular vacuolization and inflammatory cell infiltration. Additionally, SCV modulated the diversity of the gut microbiota, increasing the abundance of Allobaculum, Turicibacter, Bifidobacterium, and Akkermansia, while enriching the synthesis pathway of vitamin B12 (PWY-7377). This study is the first to repurpose sea cucumber viscera waste into a functional food, demonstrating its dual mechanism of alleviating oxidative stress by activating the Keap1-Nrf2/HO-1 antioxidant pathway and regulating the gut microbiota. These findings offer an innovative strategy for the high-value utilization of agricultural by-products and the development of multifunctional health-promoting products.

## Linked entities

- **Genes:** KEAP1 (kelch like ECH associated protein 1) [NCBI Gene 9817], GABPA (GA binding protein transcription factor subunit alpha) [NCBI Gene 2551], HMOX1 (heme oxygenase 1) [NCBI Gene 3162], HSPA1A (heat shock protein family A (Hsp70) member 1A) [NCBI Gene 3303], HSP90AA1 (heat shock protein 90 alpha family class A member 1) [NCBI Gene 3320]
- **Chemicals:** OH− (PubChem CID 961), O2− (PubChem CID 977), MDA (PubChem CID 1614)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** HO-1 [NCBI Gene 101214191], HSP70 [NCBI Gene 101210094]
- **Diseases:** inflammatory (MESH:D007249), liver damage (MESH:D056486)
- **Chemicals:** phosphorus (MESH:D010758), DPPH (MESH:C004931), calcium (MESH:D002118), polysaccharides (MESH:D011134), OH- (MESH:C031356), O2- (-), MDA (MESH:D015104), vitamin B12 (MESH:D014805)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Holothuroidea (holothurians, class) [taxon 7705]

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12649482/full.md

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Source: https://tomesphere.com/paper/PMC12649482