|J Invest Dermatol 1999 Mar;112 (3):310-6|
Procyanidin oligomers selectively and intensively promote proliferation of mouse hair epithelial cells in vitro and activate hair follicle growth in vivo.
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
Acta Derm Venereol 1998 Nov;78(6):428-32
Proanthocyanidins from grape seeds promote proliferation of mouse hair follicle cells
in vitro and convert hair cycle in vivo.
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
protein kinase C inhibitors including procyanidins promote hair growth.
By Takahashi T; Kamimura A; Shirai A; Yokoo Y
|Skin Pharmacol Appl
Skin Physiol 2000 May-Aug;13(3-4):133-42
We have previously reported that procyanidin oligomers selectively promote growth of murine hair epithelial cells in vitro and stimulate anagen induction in vivo. We report here the possible relationship between the protein kinase C-inhibiting activity of procyanidins and their hair-growing activity. Of the procyanidins, procyanidin B-2 and procyanidin C-1, which selectively inhibit protein kinase C, intensively promote hair epithelial cell proliferation in vitro and stimulate anagen induction in vivo. On the other hand, procyanidins, which inhibit both protein kinase C and A, showed relatively low activity in in vitro and in vivo evaluations. We also found that calphostin C, which is a selective inhibitor of protein kinase C, possesses hair epithelial cell growth-promoting activity in vitro and anagen phase-inducing hair-growing activity in vivo. Other selective protein kinase C inhibitors, such as hexadecylphosphocholine, palmitoyl-DL-carnitine chloride, and polymyxin B sulfate, also show marked anagen phase-inducing hair-growing activity in vivo. Nonselective protein kinase inhibitors, such as staurosporine and K252a, inhibit the growth of hair epithelial cells. 1,2-Dioctanoyl-sn-glycerol, a protein kinase C activator, dose-dependently decreases the growth of hair epithelial cells. Forskolin, an adenylate cyclase activator, promotes hair epithelial cell growth and boosts the growth-promoting effect of procyanidin B-2. It is speculated that the hair-growing activity of procyanidins is related to their protein kinase C-inhibiting activity.
studies on procyanidin B-2 for external application as a hair growing agent.
By Takahashi T; Yokoo Y; Inoue T; Ishii A
|Food Chem Toxicol
Procyanidin B-2 [epicatechin-(4beta --> 8)-epicatechin] is one of condensed tannin that exists widely in plants. We have reported previously that procyanidin B-2 possesses hair epithelial cell growth-promoting activity and stimulates anagen induction in hair cycle progression. To evaluate the safety of topical procyanidin B-2 as a hair growing agent, we examined the mutagenicity, acute subcutaneous injection, primary irritation, skin sensitization, and eye irritation of this compound. Mutagenicity tests using bacteria showed procyanidin B-2 to be non-mutagenic. Chromosomal aberration tests using CHL cells indicated that procyanidin B-2 caused polyploidy but no structural aberrations. In micronucleus tests for mutagenicity using mice, procyanidin B-2 was negative. Acute subcutaneous injection study using rats revealed no symptoms of significant injury. The lethal dose of procyanidin B-2 is greater than 2000 mg/kg (subcutaneous injection). Primary irritation tests using rabbits indicated that procyanidin B-2 containing preparation shows no primary irritation. In the guinea pig maximization test, there was no evidence of sensitization to procyanidin B-2. In primary ocular irritation tests using rabbits, procyanidin B-2 containing preparation and vehicle showed slight irritation of conjunctivae which is assumed to be caused by ethanol. It is suggested that topical procyanidin B-2 is safe and acceptable from the series of toxicological tests.