trans-3,4'-Dimethyl-3-hydroxyflavanone, a hair growth enhancing active component, decreases active transforming growth factor beta2 (TGF-beta2) through control of urokinase-type plasminogen activator (uPA) on the surface of keratinocytes.
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.
Sasajima
Michiyo
M
Global R&D, Biological Science, Kao Corporation, 2606 Akabane, Ichikaimachi, Haga, Tochigi 321-3497, Japan. sasajima.michiyo@kao.co.jp
Moriwaki
Shigeru
S
Hotta
Mitsuyuki
M
Kitahara
Takashi
T
Takema
Yoshinori
Y
D000505:Alopecia / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D044950:Flavanones / Q000494:pharmacology*; D018859:Hair Follicle / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D053781:Transforming Growth Factor beta2 / Q000037:antagonists & inhibitors*; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors*
D044950:Flavanones; D053781:Transforming Growth Factor beta2; C528105:trans-3,4'-dimethyl-3-hydroxyflavanone; D014568:Urokinase-Type Plasminogen Activator