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.

Gastric ulcer is one of the most frequent gastrointestinal disorders, and there is an increasing search for natural products that can heal ulcers and avoid their recurrence. We aimed to evaluate the gastroprotective activity of vanillin, including the investigation of anti-inflammatory activity and the modulation of gene expression. Wistar rats were orally treated with vehicle, carbenoxolone, or vanillin (25, 50, or 100 mg/kg) and orally received absolute ethanol to develop gastric ulcers. We analyzed the ulcer area, conducted histological analysis, and measured the levels of the inflammatory cytokines TNF-α, IL-6, IL-1β, and IFN-γ, and anti-inflammatory cytokine IL-10 by ELISA. We analyzed mRNA expression for NF-κB, TNF-α, and Il-10. We measured NOx levels using the Griess reaction. Our results showed similar gastroprotection for the three doses. Vanillin increased mucus production and preserved gastric mucosa integrity. The gastroprotective effect was linked to anti-inflammatory activity as a result of decreasing the levels of TNF-α, IL-6, IL-1β, and IFN-γ and increasing IL-10 levels. Vanillin downregulated the mRNA expression of NF-κB and TNF-α, upregulated the mRNA expression of Il-10, and increased NOx levels in the stomach. The gastroprotective activity of vanillin is related to the maintenance of gastric mucus and the local inflammatory response modulation.

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.