Nephrocalcinosis formation by soy isoflavones in male rats.

Isoflavones (IFs), found in the form of both aglycones and glucosides in soybean foods, induce weak estrogenic activities. Although IFs have a number of health benefits, it was previously reported that IFs cause nephrocalcinosis (NC) in the kidney of male Fischer 344 (F344) rats. The present study aims to elucidate the safety of IFs by focusing on IF-induced NC formation in rats. Fermented soybean extract (FSE) containing 420 mg/g isoflavone aglycones was orally administered to male F344 and Sprague-Dawley (SD) rats for 28 days. FSE induced NC formation in the kidney of F344 rats, but not in SD rats. However, absorption of IFs did not differ between F344 and SD rats. NC formation and its severity of FSE were histologically compared with those of soybean extract (SE) containing 518 mg/g isoflavone glucosides in F344 rats. There were no differences in the number of NC formations and the extent of calcium deposit between FSE and SE groups. To examine the dose effect of FSE on NC formation, doses of 20, 140, or 1000 mg/kg FSE were administered to F344 rats for 90 days. NC formation was observed in the 140 and 1000 mg/kg groups. These results indicated that a high dose of oral administration of IFs induced NC formation depending on the strain of rat.

Inhibitory effect of an ellagic acid-rich pomegranate extract on tyrosinase activity and ultraviolet-induced pigmentation.

A pomegranate extract (PE) from the rind containing 90% ellagic acid was tested for its skin-whitening effect. PE showed inhibitory activity against mushroom tyrosinase in vitro, and the inhibition by the extract was comparable to that of arbutin, which is a known whitening agent. PE, when administered orally, also inhibited UV-induced skin pigmentation on the back of brownish guinea pigs. The intensity of the skin-whitening effect was similar between guinea pigs fed with PE and those fed with L-ascorbic acid. PE reduced the number of DOPA-positive melanocytes in the epidermis of UV-irradiated guinea pigs, but L-ascorbic acid did not. These results suggest that the skin-whitening effect of PE was probably due to inhibition of the proliferation of melanocytes and melanin synthesis by tyrosinase in melanocytes. PE, when taken orally, may be used as an effective whitening agent for the skin.

Oral intake of proanthocyanidin-rich extract from grape seeds improves chloasma.

Chloasma (melasma), an acquired hypermelanosis, is often recalcitrant to various treatments and an amenable, as well as safe, pigment-reducing modality is needed. We investigated that the reducing effect of proanthocyanidin, a powerful antioxidant, on chloasma in a one-year open design study. Proanthocyanidin-rich grape seed extract (GSE) was orally administered to 12 Japanese woman candidates with chloasma for 6 months between August 2001 and January 2002 and to 11 of these 12 for 5 months between March and July 2002. Clinical observation, L* value (lightening) and melanin index, and size (length and width) measurements of chloasma were performed throughout the study period. The first 6 months of GSE intake improved or slightly improved chloasma in 10 of the 12 women (83%, p < 0.01) and following 5 months of intake improved or slightly improved chloasma in 6 of the 11 candidates (54%, p < 0.01). L* values also increased after GSE intake (57.8 +/- 2.5 at the start vs 59.3 +/- 2.3 at 6 months and 58.7 +/- 2.5 at the end of study). Melanin-index significantly decreased after 6 months of the intake (0.025 +/- 0.005 at the start vs 0.019 +/- 0.004 at 6 months) (p < 0.01), and also decreased at the end of study (0.021 +/- 0.005) (p < 0.05). GSE is effective in reducing the hyperpigmentation of women with chloasma. The beneficial effects of GSE was maximally achieved after 6 months and these was no further improvement after this period. The latter GSE intake for 5 months may prevent chloasma from becoming worse prior to the summer season. GSE is safe and useful for improving chloasma.

Procyanidin B1 is detected in human serum after intake of proanthocyanidin-rich grape seed extract.

To confirm the absorption of proanthocyanidin (PA) into the human body, four healthy adults were administered 2.0 g of PA-rich grape seed extract (GSE). Blood were drawn before intake and 2 h after intake. Through the enzymatic treatment of sulfatase and beta-glucuronidase, blood samples were analyzed by HPLC coupled with mass-spectrometry (LC/MS). Procyanidin B1 [epicatechin-(4beta-->8)-catechin] was detected in human serum 2 h after intake. Its concentration was 10.6 +/- 2.5 nmol/l.

Procyanidin-rich extract from grape seeds prevents cataract formation in hereditary cataractous (ICR/f) rats.

Antioxidants such as vitamin C, vitamin E, and carotenoids have been reported to prevent the progression of experimentally induced cataracts. However, little is known of the effect of procyanidins, a powerful antioxidant, on cataract formation. This paper investigates the anticataract activity of grape seed extract (GSE, which contains 38.5% procyanidins) in hereditary cataractous rats (ICR/f rats). The ICR/f rats were fed a standard diet containing 0 or 0.213% GSE [0.082% procyanidins in the diet (w/w)] for 27 days. The GSE significantly prevented and postponed development of cataract formation by evaluation of slit lamp observations of the rats' eyes. Lens weight and malondialdehyde concentration in the lens and plasma cholesteryl ester hydroperoxide (ChE-OOH) level induced by CuSO4 were significantly lower in the GSE group compared with the control group. The rats were also fed for 14 days either the diet containing 0.085% procyanidin dimer to tetramer fraction (0.085% as the procyanidins), the diet containing 0.090% procyanidin pentamer to heptamer fraction (0.085% as the procyanidins), or the diet containing 0.093% procyanidin oligomers more than decamer fraction (0.085% as the procyanidins). The ChE-OOH levels in the procyanidin pentamer to heptamer and procyanidin oligomers more than decamer groups were significantly lower than in the procyanidin dimer to tetramer group. These results suggested that procyanidins and their antioxidative metabolites prevented the progression of cataract formation by their antioxidative action. The larger molecular procyanidins in the GSE might contribute this anticataract activity.