{
  "abstract": "Delayed healing of diabetic wounds arises from a self-sustaining pathological microenvironment featuring persistent inflammation, excessive matrix degradation, impaired angiogenesis, and insufficient collagen deposition, and current single-process interventions remain unsatisfactory. Red yeast rice, produced by fermentation of rice with Monascus spp., is a traditional fermented product with documented anti-inflammatory and antioxidant activities; however, its direct extract is dominated by macromolecular and bound-state constituents with low release efficiency and poor skin permeation, which restricts its topical application. In this study, an enzymatic hydrolysate of red yeast rice (RYR-EH) was prepared by composite enzymatic hydrolysis, and the compositional changes induced by hydrolysis were characterized by widely targeted UPLC-MS/MS metabolomics. A total of 810 metabolites were detected, among which 199 showed differential accumulation after hydrolysis (179 upregulated and 20 downregulated; FC ≥ 2 or ≤0.5, VIP ≥ 1, and p < 0.05); the differential metabolites were significantly enriched (FDR < 0.05) in purine metabolism, nucleotide metabolism, ABC transporters, and the cGMP-PKG signaling pathway, a pattern consistent with hydrolysis-driven release of free amino acids, small peptides, and other low-molecular-weight constituents. In type 2 diabetic mice induced by a high-fat diet combined with low-dose streptozotocin, topical RYR-EH (2% and 5%) significantly accelerated the closure of full-thickness excisional wounds, with the 5% formulation showing more advanced closure than the 2% formulation and an effect approaching that of recombinant human epidermal growth factor (rhEGF). At the day-14 endpoint, RYR-EH treatment was associated with enhanced re-epithelialization, lower TNF-α, IL-6, and IL-1β levels in both wound tissue and serum, reduced MMP-2 and MMP-9 immunoreactivity, reduced Ki67-positive cellularity in the late-stage wound bed, increased Collagen I/III deposition, and increased VEGF/CD31 immunoreactivity. These results demonstrate that RYR-EH exerts multi-process reparative effects on diabetic wounds, simultaneously attenuating inflammation, restraining excessive matrix degradation, promoting angiogenesis, and restoring collagen deposition, and support RYR-EH as an effective multi-process topical agent for diabetic wound healing.",
  "abstract_shown": true,
  "affiliations": [
    "Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China",
    "Fujian Provincial Key Laboratory of Island Conservation and Development, Island Research Center, Ministry of Natural Resources, Pingtan 350400, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yating Du",
      "orcid": "0009-0001-4764-9865"
    },
    {
      "affs": [
        0
      ],
      "name": "Weihang Ma"
    },
    {
      "affs": [
        0
      ],
      "name": "Xinyue Chang"
    },
    {
      "affs": [
        0
      ],
      "name": "Shuting Wang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Runying Zeng",
      "orcid": "0000-0002-8134-1944"
    },
    {
      "affs": [
        0
      ],
      "name": "Nan Wu",
      "orcid": "0000-0001-5594-5042"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/47rr2me1jbjdf.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27209020",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705068/?tool=EBI",
  "id": "47rr2me1jbjdf",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/20/9020",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2742|Wound Healing and Treatments"
    ]
  ],
  "openalex": "W7221517781",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705068/pdf/?tool=EBI",
  "pmcid": "PMC13705068",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/47rr2me1jbjdf.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:55Z",
      "native_id": "10.3390/ijms27209020",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/20/9020"
    },
    {
      "first_seen": "2026-10-30T12:21:31Z",
      "native_id": "PMC:PMC13705068",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13705068"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2742|Wound Healing and Treatments",
      "subfield": "general"
    }
  ],
  "title": "Enzymatic Hydrolysate of Red Yeast Rice Accelerates Diabetic Wound Healing in Mice: Association with Modulation of Inflammatory, Matrix-Remodeling, and Angiogenesis-Related Markers",
  "title_text": "Enzymatic Hydrolysate of Red Yeast Rice Accelerates Diabetic Wound Healing in Mice: Association with Modulation of Inflammatory, Matrix-Remodeling, and Angiogenesis-Related Markers",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:31Z",
  "url": "https://research.draconitic.com/paper/47rr2me1jbjdf",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}