# Menthol-Based Cream as a Novel Therapy for Diabetic Skin Wounds

**Authors:** Ana Júlia Vieira, Fernando Pereira Beserra, Gabriel Bacil Prata, Emanuel Ricardo Monteiro Martinez, Rafael Henrique Nóbrega, Luis Fernando Barbisan, Claudia Helena Pellizzon, Ariane Leite Rozza

PMC · DOI: 10.3390/pharmaceutics18010125 · 2026-01-19

## TL;DR

Menthol-based cream significantly improved skin wound healing in diabetic rats by reducing inflammation and boosting antioxidants.

## Contribution

This study introduces menthol-based cream as a novel topical therapy for diabetic skin wounds.

## Key findings

- Menthol-based cream reduced wound area by 94% in diabetic rats.
- Menthol decreased pro-inflammatory markers and increased antioxidant enzyme activity.
- Menthol upregulated genes and proteins linked to healing and cell proliferation.

## Abstract

Background/Objectives: Diabetes mellitus impairs skin wound healing by promoting a chronic inflammatory response and increased oxidative stress. 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’ 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-α 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 Nfκb 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.

## Linked entities

- **Genes:** NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790], IL10 (interleukin 10) [NCBI Gene 3586], Mki67 (antigen identified by monoclonal antibody Ki 67) [NCBI Gene 17345], NOS3 (nitric oxide synthase 3) [NCBI Gene 4846]
- **Proteins:** NOS3 (nitric oxide synthase 3)
- **Chemicals:** menthol (PubChem CID 1254), streptozotocin (PubChem CID 29327), IL-6 (PubChem CID 165368475), IL-10 (PubChem CID 146070), GPx (PubChem CID 135460989), GR (PubChem CID 118706863), GSH (PubChem CID 124886), nitrite (PubChem CID 946)
- **Diseases:** diabetes mellitus (MONDO:0005015), type 1 diabetes mellitus (MONDO:0005147)

## Full-text entities

- **Genes:** Nos3 (nitric oxide synthase 3) [NCBI Gene 24600] {aka eNos}, Gsr (glutathione-disulfide reductase) [NCBI Gene 116686], Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, Mpo (myeloperoxidase) [NCBI Gene 303413], Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Il10 (interleukin 10) [NCBI Gene 25325] {aka IL10X, If2a}
- **Diseases:** type 1 diabetes mellitus (MESH:D003922), Diabetes mellitus (MESH:D003920), skin wounds (MESH:D014947), inflammatory (MESH:D007249)
- **Chemicals:** Nitrite (MESH:D009573), streptozotocin (MESH:D013311), Menthol (MESH:D008610), GSH (MESH:D005978), Cream (-)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Figures

11 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12845169/full.md

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Source: https://tomesphere.com/paper/PMC12845169