title: Cynaropicrin attenuates UVB-induced oxidative stress via the AhR-Nrf2-Nqo1 pathway.
abstract: Due to its antioxidant and anti-inflammatory activities, artichoke (Cynara scolymus) has been used as folk medicine to treat various diseases. Cynaropicrin (Cyn), a sesquiterpene lactone, is the major bioactive phytochemical in the artichoke; however, its pharmacological mechanism remains unknown. Because some phytochemicals exert their antioxidant activity by activating aryl hydrocarbon receptor (AhR), leading to subsequent induction of the antioxidant pathway including nuclear factor E2-related factor 2 (Nrf2) and
  quinone oxidoreductase 1 (Nqo1), we investigated whether Cyn also activates the AhR-Nrf2-Nqo1 pathway. Cyn indeed induced the activation (nuclear translocation) of AhR, leading to nuclear translocation of Nrf2 and dose-dependent upregulation of Nrf2 and Nqo1 mRNAs in human keratinocytes. The Cyn-induced AhR-Nrf2-Nqo1 activation was AhR- and Nrf2-dependent, as demonstrated by the observation that it was absent in keratinocytes transfected by siRNA against either AhR or Nrf2. In accordance with these findings, Cyn actively inhibited generation of reactive oxygen species from keratinocytes irradiated with ultraviolet B (UVB) in a Nrf2-dependent manner. Cyn also inhibited the production of proinflammatory cytokines such as interleukin 6 and tumor necrosis factor-α from UVB-treated keratinocytes. Our findings demonstrate that Cyn is a potent activator of the AhR-Nrf2-Nqo1 pathway, and could therefore be applied to prevention of UVB-induced photo aging.
authors: Department of Dermatology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: Kenjiro
authors: K
authors: Takei
authors: Department of Dermatology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: Akiko
authors: A
authors: Hashimoto-Hachiya
authors: Department of Dermatology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: Masakazu
authors: M
authors: Takahara
authors: Department of Dermatology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: Gaku
authors: G
authors: Tsuji
authors: Department of Dermatology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan; Division of Skin Surface Sensing, Department of Dermatology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: Takeshi
authors: T
authors: Nakahara
authors: Department of Dermatology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan; Division of Skin Surface Sensing, Department of Dermatology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: Masutaka
authors: M
authors: Furue
mesh_terms: D021581:Active Transport, Cell Nucleus; D000975:Antioxidants / Q000494:pharmacology*; D051792:Basic Helix-Loop-Helix Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects* / Q000201:enzymology / Q000528:radiation effects; D007783:Lactones / Q000494:pharmacology*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects* / Q000528:radiation effects; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D051792:Basic Helix-Loop-Helix Proteins; D018836:Inflammation Mediators; D015850:Interleukin-6; D007783:Lactones; D016660:NAD(P)H Dehydrogenase (Quinone); D051267:NF-E2-Related Factor 2; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D012717:Sesquiterpenes; D014409:Tumor Necrosis Factor-alpha; C111235:AHR protein, human; C508600:IL6 protein, human; C495635:NFE2L2 protein, human; C447479:NQO1 protein, human; C075687:cynaropicrin
keywords: AhR; Antioxidant; Cynaropicrin; Nqo1; Nrf2; Ultraviolet B