ArticleMolecular medicine (Cambridge, Mass.)2025
D-mannose promotes diabetic wound healing through inhibiting advanced glycation end products formation in keratinocytes.
Article in Molecular medicine (Cambridge, Mass.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed.
- Mung Bean Seed Coat Extract Promotes Diabetic Wound Healing in High-Glucose-Exposed HaCaT Keratinocytes.Antioxidants (Basel, Switzerland) · 2026Article
- Royal jelly protein hydrolysates accelerate in vitro diabetic wound healing by enhancing keratinocytes functions and suppressing macrophage-mediated inflammation.BMC complementary medicine and therapies · 2026Article
- Review
- Glucolipid metabolic disorders and ferroptosis in diabetic ulcers: pathogenic crossroads and therapeutic opportunities.Frontiers in endocrinology · 2026Review
- Multidimensional Regulatory Mechanisms and Targeted Therapeutic Strategies for Inhibited Keratinocyte Proliferation in Diabetic Wounds.Drug design, development and therapy · 2026Review
- Article
- From Control to Cure: Insights into the Synergy of Glycemic and Antibiotic Management in Modulating the Severity and Outcomes of Diabetic Foot Ulcers.International journal of molecular sciences · 2025Review
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Abstract
backgroundDiabetic chronic foot ulcers pose a significant therapeutic challenge around the world, resulting in adverse effects and complications in patients. D-mannose is enriched in cirtus peel and exerts beneficial effects among various diseases, especially against inflammation-related disorders.
methodsHere, we examined the potential effect of D-mannose during wound healing process in streptozotocin (STZ)-induced diabetes mice in vivo and by culturing keratinocytes under high glucose condition in vitro. The skin lesion healing was recorded in photos and evaluated by histochemical staining. What's more, the advanced glycation end products (AGEs) concentration in blood and mice skin was quantified. Apoptotic cells were assessed by flow cytometry and Western blotting. Inflammatory cytokines and cellular differential gene expression levels were measured by real-time PCR. The expression of the AMPK/Nrf2/HO-1 signaling-related molecules was determined by Western blotting.
resultsWe first found that topical supplementation of D-mannose remarkably improved skin wound healing in diabetes mice. Furthermore, both in vivo and in vitro experiments demonstrated that D-mannose reduced the AGEs generation. Mechanistically, D-mannose inhibited AGEs, then upregulated AMPK/Nrf2/HO-1 signaling in the context of high glucose to maintain keratinocyte normal functions, which positively influenced macrophage and fibroblast to accelerate diabetic wound healing. Noteworthily, these protective effects of D-mannose were abolished by the pretreatment with inhibitors of AGEs or AMPK.
conclusionAs far as we know, this is the first study exploring the protective role of D-mannose on diabetic wound healing via topical supplementation. We find that D-mannose protects keratinocytes from high glucose stimulation via inhibition of AGEs formation as well as orchestrates inflammatory microenvironment in diabetic wounded skin, suggesting its supplementation as a potential therapy to promote refractory wound healing in diabetic patients.
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