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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.

Abstract
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.
AuthorsMichiyo Sasajima, Shigeru Moriwaki, Mitsuyuki Hotta, Takashi Kitahara, Yoshinori Takema
JournalBiological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 31 Issue 3 Pg. 449-53 (Mar 2008) ISSN: 0918-6158 [Print] Japan
PMID18310908 (Publication Type: Journal Article)
Chemical References
  • Flavanones
  • Transforming Growth Factor beta2
  • trans-3,4'-dimethyl-3-hydroxyflavanone
  • Urokinase-Type Plasminogen Activator
Topics
  • Alopecia (drug therapy, enzymology, metabolism)
  • Blotting, Western
  • Cells, Cultured
  • Coculture Techniques
  • Enzyme-Linked Immunosorbent Assay
  • Flavanones (pharmacology)
  • Hair Follicle (drug effects, enzymology, metabolism)
  • Humans
  • Keratinocytes (drug effects, enzymology, metabolism)
  • Transforming Growth Factor beta2 (antagonists & inhibitors)
  • Urokinase-Type Plasminogen Activator (antagonists & inhibitors)

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