Proteomics Analysis of the Protective Effect of Polydeoxyribonucleotide Extracted from Sea Cucumber (Apostichopus japonicus) Sperm in a Hydrogen Peroxide-Induced RAW264.7 Cell Injury Model
Open accessAbstract
Sea cucumber viscera contain various naturally occurring active substances, but they are often underutilized during sea cucumber processing. Polydeoxyribonucleotide (PDRN) is an adenosine A2A receptor agonist that activates the A2A receptor to produce various biological effects. Currently, most studies on the activity of PDRN have focused on its anti-inflammatory, anti-apoptotic, and tissue repair properties, yet relatively few studies have investigated its antioxidant activity. In this study, we reported for the first time that PDRN was extracted from the sperm of Apostichopus japonicus (AJS-PDRN), and we evaluated its antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS), and hydroxyl radical scavenging assays. An in vitro injury model was established using H2O2-induced oxidative damage in RAW264.7 cells, and we investigated the protective effect of AJS-PDRN on these cells. Additionally, we explored the potential mechanism by which AJS-PDRN protects RAW264.7 cells from damage using iTRAQ proteomics analysis. The results showed that AJS-PDRN possessed excellent antioxidant activity and could significantly scavenge DPPH, ABTS, and hydroxyl radicals. In vitro antioxidant assays demonstrated that AJS-PDRN was cytoprotective and significantly enhanced the antioxidant capacity of RAW264.7 cells. The results of GO enrichment and KEGG pathway analysis indicate that the protective effects of AJS-PDRN pretreatment on RAW264.7 cells are primarily achieved through the regulation of immune and inflammatory responses, modulation of the extracellular matrix and signal transduction pathways, promotion of membrane repair, and enhancement of cellular antioxidant capacity. The results of a protein–protein interaction (PPI) network analysis indicate that AJS-PDRN reduces cellular oxidative damage by upregulating the expression of intracellular selenoprotein family members. In summary, our findings reveal that AJS-PDRN mitigates H2O2-induced oxidative damage through multiple pathways, underscoring its significant potential in the prevention and treatment of diseases caused by oxidative stress.
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Alternative biological sources such as plants, algae, and sea cucumbers have been explored for PDRN production.
“Alternative approaches using biological sources such as plants, algae, and sea cucumbers have also been explored for PDRN production”
From Comparison of Polynucleotide and Polydeoxyribonucleotide in Dermatology: Molecular Mechanisms and Clinical Perspectives (2025) · cites this paper as [134]
The Discussion and Methods §4.2 describe extracting PDRN from sea cucumber sperm, supporting that example of an alternative source. The paper does not report exploring plants or algae for PDRN production; the plant material mentioned in the Results is a different antioxidant, not a PDRN source. Page numbers were not available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAlthough PN and PDRN have been extensively investigated, few studies have explored alternative sources, such as plant-, microbe-, and seaweed-derived nucleotides, underscoring a substantial gap in comprehensive characterization.
“Although PN and PDRN have been extensively investigated, few studies explored alternative sources, such as plant-, microbe-, and seaweed-derived nucleotides, underscoring a substantial gap in comprehensive characterization [11,134,135,179,180,181].”
From Comparison of Polynucleotide and Polydeoxyribonucleotide in Dermatology: Molecular Mechanisms and Clinical Perspectives (2025) · cites this paper as [134]
The Introduction says PDRN is primarily derived from human placenta, salmon sperm, and trout sperm. The Discussion reports the first extraction of PDRN from sea cucumber sperm and says research on active substances in sea cucumber viscera is limited. It does not address plant-, microbe-, or seaweed-derived nucleotides or establish a general gap in their comprehensive characterization. (LLM, conf=0.84)
Experimental — accuracy not yet measuredPDRN alleviates oxidative stress in vitro in RAW264.7 macrophage injury models.
“Although these studies on the antioxidant properties of PDRN are limited, recent evidence demonstrates that PDRN alleviates oxidative stress in vitro, as shown in RAW264.7 macrophage injury models.”
From Comparison of Polynucleotide and Polydeoxyribonucleotide in Dermatology: Molecular Mechanisms and Clinical Perspectives (2025) · cites this paper as [134]
Products from alternative biological source approaches for PDRN production are often safeguarded by patents.
“and the products are often safeguarded by patents [134,163,164]”
From Comparison of Polynucleotide and Polydeoxyribonucleotide in Dermatology: Molecular Mechanisms and Clinical Perspectives (2025) · cites this paper as [134]
The Introduction and Discussion describe PDRN sources and extraction from sea cucumber sperm, but do not address patent protection. Searches for patents, proprietary products, and alternative-source production found no passage supporting the claim that such products are often patented. Page numbers were not available in our copy. (LLM, conf=0.74)
Experimental — accuracy not yet measuredAlternative biological source approaches for PDRN production tend to be more complex.
“although these approaches tend to be more complex”
From Comparison of Polynucleotide and Polydeoxyribonucleotide in Dermatology: Molecular Mechanisms and Clinical Perspectives (2025) · cites this paper as [134]
The Introduction identifies common PDRN sources, and Materials and Methods §4.2 describes extraction from sea cucumber sperm. Neither passage compares the complexity of alternative-source approaches with conventional production, so the claimed tendency cannot be verified from this paper. (LLM, conf=0.73)
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Cited by
Sorted by citations
Kim, S. T. (2025) · Pharmaceutics · doi:10.3390/pharmaceutics17081024 · Cited by 18 · see citing works
- Authors
- Shu, Z., Ji, Y., Liu, F., Jing, Y., Jiao, C., Li, Y., Zhao, Y., Wang, G., & Zhang, J.
- Affiliations
- Shandong Marine Resource and Environment Research Institute (CN)
- Corresponding author
- Wang, Gongming
- Zhang, Jian
- Venue
- Marine Drugs
- Publisher
- MDPI AG
- Published
- 2024-07-21
- Volume
- 22
- Issue
- 7
- Pages
- 325
- ISSN
- 1660-3397 (ISSN-L)
- PMC
- PMC11277713
- OpenAlex
- W4400880519
- Cited by
- 12
- References
- 3
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 1
- FWCI
- 3.86
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Marine Drugs (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Shandong Modern Agricultural Industrial Technology System Sea Cucumber Industry Innovation Team Construction Project (SDAIT-22-07, 2023YD083, ZR2020KC034)
- Yantai Science and Technology Innovation Development Program Policy Guidance Category (SDAIT-22-07, 2023YD083, ZR2020KC034)
- Key Project of Natural Science Foundation of Shandong Province (SDAIT-22-07, 2023YD083, ZR2020KC034)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Aquatic Science › Echinoderm biology and ecology
- Life Sciences › Agricultural and Biological Sciences › Aquatic Science › Seaweed-derived Bioactive Compounds
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Hydrolysis and Bioactive Peptides
- Keywords
- polydeoxyribonucleotide, Apostichopus japonicus, antioxidant activity, hydrogen peroxide-induced oxidative damage, RAW 264.7 macrophages, oxidative stress, selenoproteins, iTRAQ quantitative proteomics, protein-protein interaction network, membrane repair, extracellular matrix, immune and inflammatory responses, signaling pathways
- MeSH terms
- RAW 264.7 Cells, Animals, Antioxidants, Hydrogen Peroxide, Male, Polydeoxyribonucleotides, Sea Cucumbers, Spermatozoa, Oxidative Stress, Protective Agents, Proteomics, Stichopus, Mice
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