Tsukuba Research Laboratories, Kyowa Hakko Kogyo Co., 2, Miyukigaoka, Tsukuba, Ibaraki 305-0841, Japan.

Procyanidin B-2 is a compound we have identified in apple which acts as a growth-promoting factor on murine hair epithelial cells. This report describes our investigation of the hair-growing effects of 1% procyanidin B-2 tonic after sequential use for 4 months. A double-blind clinical trial was performed, involving a total of 29 subjects (procyanidin B-2, 19 men; placebo, 10 men). No adverse side effects were observed in either group. In the procyanidin B-2 group, 78.9% showed an increased mean value of hair diameter, whereas only 30.0% in the placebo group showed any increase (p < 0.02, Fisher's exact probability test). The increased ratio of hairs measuring more than 40 microm in diameter after 4 months of procyanidin B-2 treatment was significantly higher than that of the placebo controls (p < 0.05, two-sample-t-test). The increase in number of total hairs in the designated scalp area (0.25 cm(2)) of procyanidin B-2 subjects after a 4 month trial was significantly greater than that of the placebo controls (procyanidin-B-2, 3.67 +/- 4.09 (mean +/- SD)/0.25 cm(2); placebo, -2.54 +/- 4.00/0.25 cm(2); p < 0.001, two-sample t-test). Procyanidin B-2 therapy shows potential as a promising cure for male pattern baldness. Copyright 2001 John Wiley & Sons, Ltd.

STUDY B:
Procyanidin Oligomers selectively and intensively promote proliferation of mouse hair epithelial cells in vitro and activate hair follicle growth in vivo.

J Invest Dermatol 1999 Mar;112 (3):310-6

Takahashi T, Kamiya T, Hasegawa A, Yokoo Y

Tsukuba Research Laboratories, Kyowa Hakko Kogyo, Ibaraki, Japan.

We have previously reported that proanthocyanidins extracted from grape seeds possess growth-promoting activity toward murine hair epithelial cells in vitro and stimulate anagen induction in hair cycle progression in vivo. This report constitutes a comparison of the growth-promoting activity of procyanidin oligomers and the target cells of procyanidins in the skin. Results show that procyanidin dimer and trimer exhibit higher growth-promoting activity than the monomer. The maximum growth-promoting activity for hair epithelial cells with procyanidin B-2, an epicatechin dimer, reached about 300% (30 microM) relative to controls (= 100%) in a 5 d culture. Optimum concentration of procyanidin C-1, an epicatechin trimer, was lower than that of procyanidin B-2; the maximum growth-promoting activity of procyanidin C-1 was about 220% (3 microM). No other flavonoid compounds examined exhibit higher proliferative activities than the procyanidins. In skin constituent cells, only epithelial cells such as hair keratinocytes or epidermal keratinocytes respond to procyanidin oligomers. Topical application of 1% procyanidin oligomers on shaven C3H mice in the telogen phase led to significant hair regeneration [procyanidin B-2, 69.6% +/- 21.8% (mean +/- SD); procyanidin B-3, 80.9% +/- 13.0%; procyanidin C-1, 78.3% +/- 7.6%] on the basis of the shaven area; application of vehicle only led to regeneration of 41.7% (SD = 16.3%). In this paper, we demonstrate the hair-growing activity of procyanidin oligomers both in vitro and in vivo, and their potential for use as agents to induce hair growth.

PMID: 10084307, UI: 99181798

STUDY C:
Proanthocyanidins from grape seeds promote proliferation of mouse hair follicle cells in vitro and convert hair cycle in vivo.

Acta Derm Venereol 1998 Nov;78(6):428-32

Takahashi T, Kamiya T, Yokoo Y

Tsukuba Research Laboratories, Kyowa Hakko Kogyo Co., Ibaraki, Japan.

For the purpose of discovering natural products which possess hair growing activity, we examined about 1000 kinds of plant extracts concerning growth-promoting activity with respect to hair follicle cells. After an extensive search, we discovered that proanthocyanidins extracted from grape seeds promote proliferation of hair follicle cells isolated from mice by about 230% relative to controls (100%); and that proanthocyanidins possess remarkable hair-cycle-converting activity from the telogen phase to the anagen phase in C3H mice in vivo test systems. The profile of the active fraction of the proanthocyanidins was elucidated by thiolytic degradation and tannase hydrolysis. We found that the constitutive monomers were epicatechin and catechin; and that the degree of polymerization was 3.5. We demonstrated the possibility of using the proanthocyanidins extracted from grape seeds as agents inducing hair growth.

PMID: 9833041, UI: 99050235