A citrus polymethoxy flavonoid, nobiletin inhibits sebum production and sebocyte proliferation, and augments sebum excretion in hamsters

J Invest Dermatol. 2007 Dec;127(12):2740-8. doi: 10.1038/sj.jid.5700927. Epub 2007 Jun 28.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*
  • Sebum / metabolism*
  • Sulfonamides / pharmacology
  • Tretinoin / pharmacology
  • Triglycerides / metabolism


  • Antioxidants
  • Flavones
  • Flavonoids
  • Isoquinolines
  • Phosphatidylserines
  • Sulfonamides
  • Triglycerides
  • Tretinoin
  • nobiletin
  • Diacylglycerol O-Acyltransferase
  • Cyclic AMP-Dependent Protein Kinases
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide