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 beta (
TGF-beta), 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-beta2. However, levels of active
TGF-beta2 were reduced, suggesting the involvement of t-
flavanone in the activation pathway of
TGF-beta2. In order to investigate the effects of t-
flavanone on
TGF-beta2 activation by human keratinocytes, we evaluated the level of active
TGF-beta2 converted from the inactive form in t-
flavanone-treated human keratinocytes. The amount of active
TGF-beta2 was reduced compared with controls suggesting that t-
flavanone suppresses the
TGF-beta2 activation cascade in human keratinocytes. We then examined the activity of
urokinase-type plasminogen activator (uPA), the rate-limiting
enzyme in the
TGF-beta2 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-beta2 activation, and thereby is expected to have
therapeutic effects on other types of
alopecia in addition to
male pattern alopecia.