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

ISSN: 1875-614X (Online)
ISSN: 1871-5230 (Print)

Volume 14, 3 Issues, 2015

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Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents

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Bahar Tunctan
Department of Pharmacology
Faculty of Pharmacy
Mersin University
Mersin, 33169

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

Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, 13(1): 29-35.

Author(s): Patrizia A. d'Alessio, Massoud Mirshahi, Jean-Francois Bisson and Marie C Bene.

Affiliation: Biopark Campus Cancer, 1, mail Pr Georges Mathe, 94807 Villejuif – France.


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.


Angiogenesis inhibition, d-Limonene, inflammation inhibition, P-selectin, wound healing.

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Article Details

Volume: 13
Issue Number: 1
First Page: 29
Last Page: 35
Page Count: 7
DOI: 10.2174/18715230113126660021

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