Homoisoflavanone inhibits UVB-induced skin inflammation through reduced cyclooxygenase-2 expression and NF-kappaB nuclear localization.
BACKGROUND
Since the generation of reactive oxygen species (ROS) and release of inflammatory mediators play a major role in UVB-induced inflammation, vigorous attempts have been made for the pharmacological management of these molecules as well as for uncovering the molecular signaling pathways. Homoisoflavanone (5,7-dihydroxy-3-(3-hydroxy-4-methoxybenzyl)-chroman-4-one, HIF) extracted from Cremastra appendiculata has anti-angiogenic activities, but its effect on inflammation was unknown.


OBJECTIVE
To investigate the anti-inflammatory effects of HIF on the skin and the underlying molecular mechanisms.


METHODS
HaCaT cells were irradiated by UVB (10 mJ/cm(2)) with or without HIF. Prostaglandin E(2) (PGE(2)) level was measured by enzyme immunoassay. Activation of MAPK and production of cyclooxygenase-2 (COX-2) were determined by Western blot analysis. Localization of nuclear factor kappa B (NF-kappaB) was assessed by immunofluorescence microscopy. Hairless mice were stimulated with UVB or chemical stimulants to induce inflammatory responses in skin.


RESULTS
Pretreatment with HIF inhibited the production of intracellular ROS induced by UVB irradiation in HaCaT cells. Further analysis revealed a decrease in the level of MAPK activation and down-regulation of COX-2 expression. In addition, HIF attenuated the nuclear localization of NF-kappaB, resulting in the suppression of inflammatory molecules such as IL-6, IL-8, and TNF-alpha. Finally, topical treatment with HIF inhibited ear edema induced by UVB, 12-O-tetradecanoylphorbol-13-acetate (TPA), arachidonic acid (AA), or croton oil.


CONCLUSIONS
HIF has a strong protective effect against proinflammatory responses, implying the possibility of preventive application for inflammatory skin diseases.
Hur
Seulgi
S
Laboratory of Dermato-Immunology, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul 137-040, South Korea.
Lee
Yun Sang
YS
Yoo
Hyun
H
Yang
Jeong-Hee
JH
Kim
Tae-Yoon
TY
D000818:Animals; D016718:Arachidonic Acid / Q000009:adverse effects / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D003436:Croton Oil / Q000009:adverse effects / Q000037:antagonists & inhibitors; D051546:Cyclooxygenase 2 / Q000032:analysis; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D003872:Dermatitis / Q000188:drug therapy*; D015232:Dinoprostone / Q000032:analysis; D015536:Down-Regulation / Q000187:drug effects; D004487:Edema / Q000188:drug therapy; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors; D007529:Isoflavones / Q000737:chemistry / Q000627:therapeutic use*; D051379:Mice; D008812:Mice, Hairless; D020928:Mitogen-Activated Protein Kinases / Q000032:analysis; D016328:NF-kappa B / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000032:analysis; D012867:Skin / Q000187:drug effects / Q000201:enzymology; D013755:Tetradecanoylphorbol Acetate / Q000009:adverse effects / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D014466:Ultraviolet Rays / Q000009:adverse effects*
C554544:5,7-dihydroxy-3-(3-hydroxy-4-methoxybenzyl)chroman-4-one; D052246:Cyclooxygenase 2 Inhibitors; D018836:Inflammation Mediators; D007529:Isoflavones; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D016718:Arachidonic Acid; C020922:4-O-methyl-12-O-tetradecanoylphorbol 13-acetate; D003436:Croton Oil; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate