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Skin repair properties of d-Limonene and perillyl alcohol in murine models.

Abstract
The orange-peel derived terpene d-Limonene, probably through its metabolite, perillyl alcohol (POH), has been reported to have tissue-repair properties. Two murine models of respectively 12-O-Tetradecanoylphorbol-13-Acetate (TPA)-induced dermatitis and mechanical skin lesion were used here to assess the efficacy of d-Limonene or POH applied topically. Macroscopic and microscopic evaluation of skin lesions was performed as well as that of P-selectin expression, together with measurements of serum concentrations of IL-1β, IL-6 and TNF-α in the first model. Healing and angiogenesis around the scar were examined in the second model. Because differences in angiogenesis were noted, the effect of both d-Limonene and POH was further tested on an in vitro model of endothelial microtubules formation. Both d-Limonene and POH reduced the severity and extension of TPA-induced skin lesions with significantly lowered macroscopic and microscopic scores (p<0.04 in both cases). Moreover, the expression of P-selectin induced by TPA was abrogated by POH and significantly lower serum concentrations of IL-6 and TNF-α were observed in d-Limonene- and POH-treated mice (p<0.04 and 0.03). In the second model, tissue regeneration was improved, especially by POH, and was clearly associated with reduced neovascularization. This surprising anti-angiogenic effect was confirmed in the matrigel model of endothelial microtubules formation. These studies show that d-Limonene and POH demonstrate significant anti-inflammatory effects in murine dermal inflammation and wound-healing. The decreased systemic cytokine production as well as a consistent inhibition of endothelial P-selectin expression and neo-vascularization induced by these terpenic compounds contribute to their healing effects on the epidermal barrier.
AuthorsPatrizia A d'Alessio, Massoud Mirshahi, Jean-Francois Bisson, Marie C Bene
JournalAnti-inflammatory & anti-allergy agents in medicinal chemistry (Antiinflamm Antiallergy Agents Med Chem) Vol. 13 Issue 1 Pg. 29-35 (Mar 2014) ISSN: 1875-614X [Electronic] United Arab Emirates
PMID24160248 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Angiogenesis Inhibitors
  • Cyclohexenes
  • Cytokines
  • Inflammation Mediators
  • Monoterpenes
  • P-Selectin
  • Phorbol Esters
  • Terpenes
  • perillyl alcohol
  • Limonene
Topics
  • Administration, Cutaneous
  • Angiogenesis Inhibitors (therapeutic use)
  • Animals
  • Cells, Cultured
  • Citrus sinensis
  • Cyclohexenes (therapeutic use)
  • Cytokines (blood)
  • Dermatitis, Irritant (drug therapy)
  • Disease Models, Animal
  • Endothelium (drug effects, pathology)
  • Female
  • Fruit
  • Gene Expression Regulation (drug effects)
  • Humans
  • Inflammation Mediators (blood)
  • Limonene
  • Mice
  • Mice, Hairless
  • Microtubules (drug effects)
  • Monoterpenes (therapeutic use)
  • P-Selectin (metabolism)
  • Phorbol Esters (administration & dosage)
  • Phytotherapy
  • Skin (drug effects, injuries, pathology)
  • Terpenes (therapeutic use)
  • Wound Healing (drug effects)

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