抄録
trans-3,4′-Dimethyl-3-hydroxyflavanone (t-flavanone) is a synthetic compound with hair growth enhancing activity that is effective against male pattern alopecia. t-Flavanone was designed as a derivative of astilbin, the active hair growth enhancing component of Hypericum perforatum extracts. This study was designed to elucidate the mechanism of hair growth enhancement by t-flavanone. We investigated the effects of t-flavanone on transforming growth factor β (TGF-β), a known catagen-inducing factor induced in hair papilla cells by male hormone. When t-flavanone was added to cocultures of human hair papilla cells and human keratinocytes, there was no change in the total level of TGF-β2. However, levels of active TGF-β2 were reduced, suggesting the involvement of t-flavanone in the activation pathway of TGF-β2. In order to investigate the effects of t-flavanone on TGF-β2 activation by human keratinocytes, we evaluated the level of active TGF-β2 converted from the inactive form in t-flavanone-treated human keratinocytes. The amount of active TGF-β2 was reduced compared with controls suggesting that t-flavanone suppresses the TGF-β2 activation cascade in human keratinocytes. We then examined the activity of urokinase-type plasminogen activator (uPA), the rate-limiting enzyme in the TGF-β2 activation cascade, in t-flavanone-treated human keratinocytes. We found that t-flavanone reduces uPA activity on the keratinocyte surface. t-Flavanone is a hair growth enhancing component that has a novel mechanism of action which suppresses TGF-β2 activation, and thereby is expected to have therapeutic effects on other types of alopecia in addition to male pattern alopecia.
