title: Prevention of UVB-induced photoinflammation and photoaging by a polymethoxy flavonoid, nobiletin, in human keratinocytes in vivo and in vitro.
abstract: Exposure to ultraviolet B (UVB) irradiation induces acute skin inflammation such as erythema (sunburn) and edema, and prostaglandin (PG)E2 in the epidermis plays an important role as its prominent mediator. In the present study, we investigated the effect of nobiletin (5,6,7,8,3',4'-hexamethoxy flavone) from Citrus depressa, on the production of PGE2 in UVB-irradiated human keratinocytes. When keratinocytes were irradiated with 60mJ of UVB/cm2, the production and gene expression of cyclooxygenase (COX)-2, but not COX-1, were augmented along with an increase in PGE2 levels. The augmented COX-2 production was transcriptionally suppressed by nobiletin. In addition, neither the release of [14C]arachidonic acid from membrane phospholipids nor the gene expression of cytosolic phospholipase A2 (cPLA2) was altered in UVB-irradiated human keratinocytes. However, nobiletin was found to inhibit the release of [14C]arachidonic acid by decreasing the Ca2+ -dependent activity of cPLA2. Furthermore, topical treatment of nobiletin on the skin of the back prevented the UVB-induced increase of transepidermal water loss and hyperplasia of the epidermis in hairless mice. Therefore, these results suggest that nobiletin inhibits the UVB-induced production of PGE2 not only by suppressing the expression of COX-2 but also by decreasing the activity of cPLA2 in human keratinocytes. Furthermore, nobiletin may be useful as a novel sunscreen reagent to be applied for protection against photoinflammation and photoaging.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tanaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Sato
authors.forename: Noriko
authors.initials: N
authors.lastname: Akimoto
authors.forename: Masamichi
authors.initials: M
authors.lastname: Yano
authors.forename: Akira
authors.initials: A
authors.lastname: Ito
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D004817:Epidermis / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D047309:Flavones; D005419:Flavonoids / Q000494:pharmacology*; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D008565:Membrane Proteins; D051379:Mice; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D047309:Flavones; D005419:Flavonoids; D007527:Isoenzymes; D008565:Membrane Proteins; C008661:nobiletin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone