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Summary Following consecutive 12-wk administration of tablets containing 0, 200 or 400 mg grape seed extract (calculated as proanthocyanidin) to 61 healthy subjects with LDL cholesterol (LDL-C) levels of 100 to 180 mg/dL, effects of such treatment compared to administration of placebo tablets on malondialdehyde-modified LDL (MDA-LDL), representing one oxidized type of LDL, were investigated by a single blind method. MDA-LDL level in the 200 mg (calculated as proanthocyanidin) group was significantly ( p ϭ 0.008) reduced compared to the basal level, 12 wk after the start of administration. In the 400 mg (calculated as proanthocyanidin) group, a significant decrease in MDA-LDL level compared to the basal level was found 6 and 12 wk after the start of administration (6 wk: p ϭ 0.015, 12 wk: p ϭ 0.009). Subjects with high levels of MDA-LDL/ApoB (MDA-LDL/ApoB Ն 100 mU/mL) in the 200 mg group showed significantly ( p ϭ 0.011) reduced MDA-LDL levels at 12 wk after the start of administration. In the 400 mg group, significant decreases in MDA-LDL level compared to the basal level were seen 6 and 12 wk after the start of administration (6 wk: p ϭ 0.001, 12 wk: p Ͻ 0.001); and at week 6, significantly ( p ϭ 0.048) lower values were observed compared to those in patients who took placebo tablets (0 mg proanthocyanidin). In subjects demonstrating the least body weight changes during the test period (less than ± 1.0 kg) in the 400 mg group, there was an increasing trend ( p ϭ 0.088) in adiponectin levels 12 wk after the start of treatment. These results suggested that tablets containing grape seed extract exerted reducing effects on oxidized LDL, and might be useful in preventing lifestylerelated diseases such as arteriosclerosis.

Antioxidants such as vitamins C and E have been reported to inhibit the progression of ultraviolet (UV) radiation-induced pigmentation in the skin of hairless mice. However, little is known of the lightening effect of proanthocyanidin, a powerful polyphenolic antioxidant, on UV-induced pigmentation of the skin. We investigated the lightening effect of oral administration of a proanthocyanidin-rich grape seed extract (GSE) using guinea pigs with UV-induced pigmentation. These pigmented guinea pigs were fed diets containing 1% GSE or 1% vitamin C (w/w) for 8 weeks. GSE-feeding had an apparent lightening effect on the guinea pigs' pigmented skin. Histologic evaluation demonstrated a decrease in the number of 3,4-dihydroxyphenylalanine (DOPA)-positive melanocytes as well as 8-hydroxy-2'-deoxyguanosine (8-OHdG)-positive, Ki-67-positive, proliferating cell nuclear antigen (PCNA)-positive melanin-containing cells in the basal epidermal layer of the UV-irradiated skin in GSE-fed guinea pigs. In contrast, these parameters did not change in the skin of vitamin C-fed or control guinea pigs. GSE inhibited the activity of mushroom tyrosinase and also inhibited melanogenesis without inhibiting the growth of cultured B16 mouse melanoma cells. In conclusion, we demonstrated that oral administration of GSE is effective in lightening the UV-induced pigmentation of guinea pig skin. This effect may be related to the inhibition of melanin synthesis by tyrosinase in melanocytes and the reactive oxygen species (ROS)-related proliferation of melanocytes.

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