Procyanidin Oligomers Counteract TGF-β<sub>1</sub>- and TGF-β<sub>2</sub>-Induced Apoptosis in Hair Epithelial Cells: An Insight into Their Mechanisms

Procyanidin oligomers are polyphenol compounds we have identified in apples and barley which have hair growth stimulant effects, and which are able to promote hair epithelial cell growth and induce anagen induction of the hair cycle in the in vivo murine model. For the purpose of examining the hair-growing mechanisms of procyanidin oligomers, we examined their relationship to the TGF-beta signal pathway, known to be a regulator of catagen induction, and the mitogen-activated protein kinase cascade linked to cell proliferation. Addition of TGF-beta(1) or TGF-beta(2) to hair epithelial cell cultures dose-dependently decreased cell growth and induced apoptosis; however, addition of procyanidin B-2 to the culture neutralized the growth-inhibiting effects of both TGF-beta(1) and TGF-beta(2) and protected the cells from apoptosis. The same effects were observed with procyanidin B-3. We confirmed that procyanidin B-2 upregulates the expression of MEK-1/2 in cultured murine hair epithelial cells. We speculate that the hair-growing activity of procyanidin oligomers is at least linked to their growth-promoting effects on hair epithelial cells that follow MEK activation and their protective action on TGF-beta(1)- or TGF-beta(2)-induced apoptosis that is assumed to trigger catagen induction in the hair cycle.