title: Luteolin suppresses UVB-induced photoageing by targeting JNK1 and p90 RSK2.
abstract: Multiple lines of evidence suggest that natural compounds can prevent skin ageing induced by ultraviolet light. Luteolin, a bioactive compound found in chilli, onion, broccoli, celery and carrot, has been reported to exhibit anti-photoageing effects in vitro. However, the molecular targets and mechanisms of luteolin are still poorly understood. In this study, we sought to investigate the effects of luteolin on UVB-induced photoageing and the molecular mechanisms involved, using HaCaT human keratinocytes and SKH-1 hairless mice. Luteolin was found to inhibit UVB-induced MMP-1 expression in HaCaT cells, as well as UVB-induced activation of AP-1, a well-known transcription factor targeting the MMP-1 promoter region, as well as c-Fos and c-Jun, which comprise the AP-1 complex. In contrast, Western blot data showed that UVB-induced phosphorylation of JNK, ERK and p90RSK was not inhibited by luteolin. In vitro kinase assay data revealed that luteolin significantly suppressed JNK1 and p90RSK activity, but not that of JNK2 and ERK2. Pull-down assays showed that luteolin binds JNK1 in an ATP-competitive manner and p90RSK2 in an ATP-independent manner. Luteolin also inhibited UVB-induced wrinkle formation and MMP-13 expression, a rodent interstitial collagenase in mouse skin, in vivo. Taken together, our observations suggest that luteolin exhibits anti-photoageing effects in vitro and in vivo and may have potential as a treatment for the prevention of skin ageing.
authors.affiliation: WCU Biomodulation Major, Center for Food and Bioconvergence, Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.
authors.forename: Sung H
authors.initials: SH
authors.lastname: Lim
authors.forename: Sung K
authors.initials: SK
authors.lastname: Jung
authors.forename: Sanguine
authors.initials: S
authors.lastname: Byun
authors.forename: Eun J
authors.initials: EJ
authors.lastname: Lee
authors.forename: Jung A
authors.initials: JA
authors.lastname: Hwang
authors.forename: Sang G
authors.initials: SG
authors.lastname: Seo
authors.forename: Yeong A
authors.initials: YA
authors.lastname: Kim
authors.forename: Jae G
authors.initials: JG
authors.lastname: Yu
authors.forename: Ki W
authors.initials: KW
authors.lastname: Lee
authors.forename: Hyong J
authors.initials: HJ
authors.lastname: Lee
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects / Q000528:radiation effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects; D008156:Luciferases / Q000378:metabolism; D047311:Luteolin / Q000737:chemistry / Q000494:pharmacology*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D051379:Mice; D008812:Mice, Hairless; D048055:Mitogen-Activated Protein Kinase 8 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008954:Models, Biological; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects / Q000528:radiation effects; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015595:Skin Aging / Q000187:drug effects / Q000528:radiation effects*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D000255:Adenosine Triphosphate; D008156:Luciferases; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D048049:Extracellular Signal-Regulated MAP Kinases; D048055:Mitogen-Activated Protein Kinase 8; D053509:Matrix Metalloproteinase 13; D020781:Matrix Metalloproteinase 1; D047311:Luteolin
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