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Nutrition and Disease

Olive Leaf Extract and Its Main Component Oleuropein Prevent Chronic Ultraviolet B Radiation-Induced Skin Damage and Carcinogenesis in Hairless Mice^1,2,3

⁴ Division of Biochemical Pharmacology, Department Basic Medical Research, Ehime University Graduate School of Medicine, Toon City Ehime 791-0295, Japan ⁵ Division of Functional Histology, Department of Functional Biomedicine, Ehime University Graduate School of Medicine, Toon City Ehime 791-0295, Japan

Chronic exposure to solar UV radiation damages skin, increasing its thickness and reducing its elasticity, and causes skin cancer. Our aim in this study was to examine the effects of an olive leaf extract and its component oleuropein on skin damage and the incidence of skin tumors caused by long-term UVB irradiation in hairless mice. Male hairless mice (5 wk old) were divided into 6 groups, including a non-UVB group, a vehicle-treated UVB group (control), 2 olive leaf extract-treated UVB groups, and 2 oleuropein-treated UVB groups. Five groups were UVB irradiated (36–180 mJ/cm²) 3 times each week for 30 wk and skin thickness and elasticity after UVB irradiation were measured every week. Olive leaf extract (300 and 1000 mg/kg) and oleuropein (10 and 25 mg/kg) were administered orally twice daily every day for 30 wk. The extract and oleuropein significantly inhibited increases in skin thickness and reductions in skin elasticity, and skin carcinogenesis and tumor growth. Furthermore, they prevented increases in the expression of matrix metalloproteinase (MMP)-2, MMP-9, and MMP-13 as well as in levels of vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) in the skin. Based on histological evaluation, they prevented increases in the expression of Ki-67 and CD31-positive cells induced by the irradiation. These results suggest that the preventative effects of the olive leaf extract and oleuropein on chronic UVB-induced skin damage and carcinogenesis and tumor growth may be due to inhibition of the expression of VEGF, MMP-2, MMP-9, and MMP-13 through a reduction in COX-2 levels.

^* To whom correspondence should be addressed. E-mail: yokim{at}m.ehime-u.ac.jp.

Manuscript received 22 January 2009. Initial review completed 9 March 2009. Revision accepted 19 August 2009.