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This study aimed to investigate the healing potential of menthol in skin wounds of diabetic rats. Methods: A single dose of streptozotocin (50 mg\/kg, i.p.) induced type 1 diabetes mellitus in male Wistar rats. After nine days, a skin wound was made on the rats\u2019 back and treated with vehicle, insulin-based cream (0.5 U\/g), or menthol-based cream (0.5%) for 14 days. After the euthanasia, the wound area was destined for assays of anti-inflammatory and antioxidant activity, protein expression levels by Western blotting, measurement of MPO activity, and quantitative mRNA expression. Nitrite levels were measured in blood plasma. Results: The group treated with menthol-based cream decreased the wound area by 94%. Also, menthol reduced the levels of TNF-\u03b1 and IL-6 and increased IL-10 levels, besides stimulating the activity of antioxidant enzymes SOD, GPx, and GR, and enhancement in GSH and nitrite levels. Menthol downregulated the expression of Nf\u03bab and upregulated the Il10 and Ki67 gene expression and the eNOS protein expression. Conclusions: Topically applied menthol accelerated the skin wound healing in diabetic rats through anti-inflammatory and antioxidant activities and increased cell proliferation, supporting its potential as a therapeutic strategy for diabetic wound management.<\/jats:p>","DOI":"10.3390\/pharmaceutics18010125","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T08:36:33Z","timestamp":1768898193000},"page":"125","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Menthol-Based Cream as a Novel Therapy for Diabetic Skin Wounds"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3851-1861","authenticated-orcid":false,"given":"Ana J\u00falia","family":"Vieira","sequence":"first","affiliation":[{"name":"Department of Structural and Functional Biology, Institute of Biosciences, S\u00e3o Paulo State University (UNESP), Dr. Antonio Celso W Zanin Street, 250, Botucatu 18618-689, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando Pereira","family":"Beserra","sequence":"additional","affiliation":[{"name":"Department of Structural and Functional Biology, Institute of Biosciences, S\u00e3o Paulo State University (UNESP), Dr. Antonio Celso W Zanin Street, 250, Botucatu 18618-689, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3840-7749","authenticated-orcid":false,"given":"Gabriel Bacil","family":"Prata","sequence":"additional","affiliation":[{"name":"Department of Structural and Functional Biology, Institute of Biosciences, S\u00e3o Paulo State University (UNESP), Dr. Antonio Celso W Zanin Street, 250, Botucatu 18618-689, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuel Ricardo Monteiro","family":"Martinez","sequence":"additional","affiliation":[{"name":"Department of Structural and Functional Biology, Institute of Biosciences, S\u00e3o Paulo State University (UNESP), Dr. Antonio Celso W Zanin Street, 250, Botucatu 18618-689, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9796-5076","authenticated-orcid":false,"given":"Rafael Henrique","family":"N\u00f3brega","sequence":"additional","affiliation":[{"name":"Department of Structural and Functional Biology, Institute of Biosciences, S\u00e3o Paulo State University (UNESP), Dr. Antonio Celso W Zanin Street, 250, Botucatu 18618-689, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2180-1814","authenticated-orcid":false,"given":"Luis Fernando","family":"Barbisan","sequence":"additional","affiliation":[{"name":"Department of Structural and Functional Biology, Institute of Biosciences, S\u00e3o Paulo State University (UNESP), Dr. Antonio Celso W Zanin Street, 250, Botucatu 18618-689, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia Helena","family":"Pellizzon","sequence":"additional","affiliation":[{"name":"Department of Structural and Functional Biology, Institute of Biosciences, S\u00e3o Paulo State University (UNESP), Dr. Antonio Celso W Zanin Street, 250, Botucatu 18618-689, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariane Leite","family":"Rozza","sequence":"additional","affiliation":[{"name":"Department of Structural and Functional Biology, Institute of Biosciences, S\u00e3o Paulo State University (UNESP), Dr. Antonio Celso W Zanin Street, 250, Botucatu 18618-689, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,19]]},"reference":[{"key":"ref_1","unstructured":"International Diabetes Federation (2025). 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