Document Detail


A citrus polymethoxy flavonoid, nobiletin inhibits sebum production and sebocyte proliferation, and augments sebum excretion in hamsters.
MedLine Citation:
PMID:  17597820     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Acne vulgaris is characterized by excess sebum production, and apart from all-trans retinoic acid (atRA) or 13-cis retinoic acid (13-cisRA), there are few effective agents for acne therapy that directly suppresses sebaceous lipogenesis. In this study, we demonstrated that topical application of a citrus polymethoxy flavonoid, nobiletin, to hamster auricles decreased skin surface triacylglycerols (TG) level and the size of sebaceous glands along with inhibition of diacylglycerol acyltransferase (DGAT)-dependent TG synthesis and sebocyte proliferation. The inhibitory actions were similar to that observed with atRA and 13-cisRA in hamster sebocytes. The antilipogenic and antiproliferative actions of nobiletin were also reproduced in UVB (5.4 kJ/m2)-irradiated hamsters, which showed aberrant enhancement of sebum accumulation and sebaceous enlargement. Furthermore, nobiletin, but not 13-cisRA, augmented sebum excretion along with increases in intracellular cAMP level, protein kinase A (PKA) activation, and apoptosis-independent phosphatidylserine (PS) externalization in cell membrane. These phenomena were reproduced by forskolin and inhibited by a PKA inhibitor, H-89. These results provide early evidence that nobiletin is an effective candidate for acne therapy through mechanisms that include the inhibition of DGAT-dependent TG synthesis and sebocyte proliferation, and the progression of apoptosis-independent and PS-externalization-dependent sebum excretion by PKA activation.
Authors:
Takashi Sato; Aiko Takahashi; Mika Kojima; Noriko Akimoto; Masamichi Yano; Akira Ito
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-06-28
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  127     ISSN:  1523-1747     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  2007 Dec 
Date Detail:
Created Date:  2007-11-16     Completed Date:  2007-12-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2740-8     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Molecular Biology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan. satotak@ps.toyaku.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Animals
Antioxidants / therapeutic use
Cell Membrane / metabolism
Cell Proliferation
Cricetinae
Cyclic AMP-Dependent Protein Kinases / metabolism
Diacylglycerol O-Acyltransferase / metabolism
Flavones / therapeutic use*
Flavonoids / therapeutic use*
Isoquinolines / pharmacology
Models, Biological
Phosphatidylserines / chemistry
Sebum / cytology*,  metabolism*
Sulfonamides / pharmacology
Tretinoin / pharmacology
Triglycerides / metabolism
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Flavones; 0/Flavonoids; 0/Isoquinolines; 0/Phosphatidylserines; 0/Sulfonamides; 0/Triglycerides; 127243-85-0/H 89; 302-79-4/Tretinoin; 478-01-3/nobiletin; EC 2.3.1.20/Diacylglycerol O-Acyltransferase; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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