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Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents)
ISSN (Print): 1871-5230
ISSN (Online): 1875-614X
VOLUME: 13
ISSUE: 1
DOI: 10.2174/18715230113126660021









Skin Repair Properties of d-Limonene and Perillyl Alcohol in Murine Models

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Author(s): Patrizia A. d'Alessio, Massoud Mirshahi, Jean-Francois Bisson and Marie C. Bene
Pages 29-35 (7)
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.
Keywords:
Angiogenesis inhibition, d-Limonene, inflammation inhibition, P-selectin, wound healing.
Affiliation:
Biopark Campus Cancer, 1, mail Pr Georges Mathe, 94807 Villejuif – France.