William Osler stated that “A man is as old as his arteries.” Now, it has been known that attenuation of the production of reactive oxygen species and inhibition of inflammatory pathways play a central role in the anti-aging therapy for vasculature. Dysfunction of endothelial cells (EC) has been known to promote abnormal vascular growth such as that in atherosclerosis and arteriosclerosis and postulated as an initial trigger of the progression of atherosclerosis in patients with diabetes mellitus, hypertension and hyperlipidemia. We and others have previously demonstrated high D-glucose directly induced apoptosis through activation of the bax-caspase proteases pathway in human EC. Although it has been known for years that vascular cells can release a large amount ROS, including superoxide, hydrogen peroxide, and nitric oxide, the role of oxidative stress in atherogenesis has received increasing attention in recent years. Recent works strongly suggest that NADPH oxidase is a major source of superoxide in cardiovascular cells oxidative stress can be involved in the process of endothelial dysfunction. From a view of these molecular mechanisms, HMG-CoA reductase inhibitor (stains) might inhibit the NADPH oxidase activation through inhibition of Rac activity and finally prevent the increase in ROS production in diabetes. Actually, recent clinical trial suggests that statins prevent several vascular events in patients with type 2 diabetes without high concentration of LDL-cholesterol. This pleiotropic effect of statins can improve endothelial dysfunction through Nitric Oxide production and/or anti-oxidant effect in diabetes patients.

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Numerous studies have been conducted to research substances useful for preventing or reducing pigmentation in the skin. Pigment spot is a serious cosmetic concern, particularly for the Asian elderly. Oral ingestion of antioxidant supplements is known to prevent skin pigmentation. Glutathione is an intracellular antioxidant that plays an important role in cell protection against oxidative stress and shows antimelanogenic activity. In our previous study, it was shown that olive leaf extract stimulated intracellular glutathione synthesis in human fibroblasts, melanocytes and keratinocytes. Here, a double-blind placebo-controlled study was performed to investigate whether the ingestion of a supplement containing olive leaf extract, L-cystine and ascorbic acid affects tanning of skin induced by ultraviolet (UV) irradiation. We determined the minimal erythema dose (MED) in 24 healthy volunteers before and after supplementation. Small sites on the subjects'arms were exposed to UV light for three successive days, and subjects were then administered tablets containing 47.7 mg olive leaf extract, 40.0 mg L-cystine and 50.0 mg ascorbic acid every day for 8 weeks. The present study showed that the subjects'MED increased significantly after an 8-week course of supplementation. The increment of skin lightness at the sites of UV irradiation from Day 10 to Day 17 was significantly higher in the test sample group than in subjects who received a placebo. These results suggest that the supplement containing olive leaf extract, L-cystine and ascorbic acid reduces UV-induced erythema and tanning by its antioxidative activity.

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