title: Rutin inhibits UVB radiation-induced expression of COX-2 and iNOS in hairless mouse skin: p38 MAP kinase and JNK as potential targets.
abstract: Exposure to ultraviolet B (UVB) radiation, a complete environmental carcinogen, induces oxidative and inflammatory skin damage, thereby increasing the risk of skin carcinogenesis. The antioxidant and anti-inflammatory activities of a wide variety of plant polyphenols have been reported. Rutin (3-rhamnosyl-glucosylquercetin), a polyphenol present in many edible plants, possesses diverse pharmacological properties including antioxidant, anti-inflammatory, antimutagenic and anticancer activities. The present study was aimed to investigate the effects of rutin on UVB-induced inflammation in mouse skin in vivo. Topical application of rutin onto the dorsal skin of female HR-1 hairless mice 30 min prior to UVB irradiation diminished epidermal hyperplasia and the levels of proteins modified by 4-hydroxynonenal, which is a biochemical hallmark of lipid peroxidation. Topical application of rutin also significantly inhibited UVB-induced expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), two representative inflammatory enzymes, in hairless mouse skin. Rutin inhibited the DNA binding of activator protein-1 (AP-1) and phosphorylation of signal transducer and activator of transcription-3 (STAT3) in mouse skin exposed to UVB. Moreover, rutin attenuated UVB-induced phosphorylation of p38 mitogen-activated protein (MAP) kinase and c-Jun-N-terminal kinase (JNK). Pharmacological inhibition of p38 MAP kinase and JNK decreased UVB-induced expression of COX-2 in mouse skin. Taken together, these findings suggest that rutin exerts anti-inflammatory effects in UVB-irradiated mouse skin by inhibiting expression of COX-2 and iNOS, which is attributable to its suppression of p38 MAP kinase and JNK signaling responsible for AP-1 activation.
authors.affiliation: Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Ki-Seok
authors.initials: KS
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Keimyung University, Daegu 704-701, South Korea.
authors.forename: Joydeb Kumar
authors.initials: JK
authors.lastname: Kundu
authors.affiliation: College of Pharmacy, Keimyung University, Daegu 704-701, South Korea.
authors.forename: Kyung-Soo
authors.initials: KS
authors.lastname: Chun
authors.affiliation: Department of Food and Nutrition, Sungsin Women's University, Seoul 136-742, South Korea.
authors.forename: Hye-Kyung
authors.initials: HK
authors.lastname: Na
authors.affiliation: Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 151-742, South Korea; Cancer Research Institute, Seoul National University, Seoul, South Korea. Electronic address: surh@snu.ac.kr.
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Surh
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006965:Hyperplasia; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008812:Mice, Hairless; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D012431:Rutin / Q000494:pharmacology*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D050794:STAT1 Transcription Factor; D018808:Transcription Factor AP-1; D012431:Rutin; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: AP-1; Cyclooxygenase-2; Inducible nitric oxide synthase; Mouse skin carcinogenesis; Rutin; UVB-induced skin cancer