The skin is the biggest organ of human body which acts as a protective barrier against deleterious agents. When this barrier is damaged, the organism promotes the healing process with several molecular and cellular mechanisms, in order to restore the physiological structure of the skin. The physiological control of wound healing depends on the correct balance among its different mechanisms. Any disruption in the balance of these mechanisms can lead to problems and delay in wound healing. The impairment of wound healing is linked to underlying factors as well as aging, nutrition, hypoxia, stress, infections, drugs, genetics, and chronic diseases. Over the years, numerous studies have been conducted to discover the correct approach and best therapies for wound healing, including surgical procedures and non-surgical treatments such as topical formulations, dressings, or skin substitutes. Thus, this general approach is necessary to facilitate the direction of further studies. This work provides updated concepts of physiological mechanisms, the factors that can interfere, and updated treatments used in skin wound healing.

Wound healing involves inflammatory, proliferative, and remodeling phases, in which various cells and chemical intermediates are involved. This study aimed to investigate the skin wound healing potential of menthol, as well as the mechanisms involved in its effect, after 3, 7, or 14 days of treatment, according to the phases of wound healing. Skin wound was performed in the back of Wistar rats, which were topically treated with vehicle cream; collagenase-based cream (1.2 U/g); or menthol-based cream at 0.25%, 0.5%, or 1.0% over 3, 7, or 14 days. Menthol cream at 0.5% accelerated the healing right from the inflammatory phase (3 days) by decreasing mRNA expression of inflammatory cytokines TNF-α and Il-6. At the proliferative phase (7 days), menthol 0.5% increased the activity of antioxidant enzymes SOD, GR, and GPx, as well as the level of GSH, in addition to decreasing the levels of inflammatory cytokines TNF-α, IL-6, and IL-1β and augmenting mRNA expression for Ki-67, a marker of cellular proliferation. At the remodeling phase (14 days), levels of inflammatory cytokines were decreased, and the level of Il-10 and its mRNA expression were increased in the menthol 0.5% group. Menthol presented skin wound healing activity by modulating the antioxidant system of the cells and the inflammatory response, in addition to stimulating epithelialization.

Skin wound healing is a complex process that requires the mutual work of cellular and molecular agents to promote tissue restoration. In order to improve such a process, especially in cases of impaired healing (e.g., diabetic ulcer, chronic wounds), there is a search for substances with healing properties and low toxicity: two features that some natural products—such as the bee product named propolis—exhibit. Propolis is a resinous substance obtained from plant resins and exudates with antioxidant, anti-inflammatory, and antitumoral activities, among other biological ones. Based on the previously reported healing actions of different types of propolis, the Brazilian red propolis (BRP) was tested for this matter. A skin wound excision model in male Wistar rats was performed using two topical formulations with 1% red propolis as treatments: hydroalcoholic extract and Paste. Macroscopical, histological and immunohistochemical analysis were performed, revealing that red propolis enhanced wound contraction, epithelialization, reduced crust formation, and modulated the distribution of healing associated factors, mainly collagen I, collagen III, MMP-9, TGF-β3 and VEGF. Biochemical analysis with the antioxidants SOD, MPO, GSH and GR showed that propolis acts similarly to the positive control, collagenase, increasing these molecules’ activity. These results suggest that BRP promotes enhanced wound healing by modulating growth factors and antioxidant molecules related to cutaneous wound healing.

The skin is essential to the integrity of the organism. The disruption of this organ promotes a wound, and the organism starts the healing to reconstruct the skin. Copaifera langsdorffii is a tree used in folk medicine to treat skin affections, with antioxidant and anti-inflammatory properties. In our study, the oleoresin of the plant was associated with nanostructured lipid carriers, aiming to evaluate the healing potential of this formulation and compare the treatment with reference drugs used in wound healing. Male Wistar rats were used to perform the excision wound model, with the macroscopic analysis of wound retraction. Skin samples were used in histological, immunohistochemical, and biochemical analyses. The results showed the wound retraction in the oleoresin-treated group, mediated by α-smooth muscle actin (α-SMA). Biochemical assays revealed the anti-inflammatory mechanism of the oleoresin-treated group, increasing interleukin-10 (IL-10) concentration and decreasing pro-inflammatory cytokines. Histopathological and immunohistochemical results showed the improvement of re-epithelialization and tissue remodeling in the Copaifera langsdorffii group, with an increase in laminin-γ2, a decrease in desmoglein-3 and an increase in collagen remodeling. These findings indicate the wound healing potential of nanostructured lipid carriers associated with Copaifera langsdorffii oleoresin in skin wounds, which can be helpful as a future alternative treatment for skin wounds.

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.