Cynaropicrin attenuates UVB-induced oxidative stress via the AhR-Nrf2-Nqo1 pathway

Toxicol Lett. 2015 Apr 16;234(2):74-80. doi: 10.1016/j.toxlet.2015.02.007. Epub 2015 Feb 11.

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

Nad(p)h: 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.

Keywords: AhR; Antioxidant; Cynaropicrin; Nqo1; Nrf2; Ultraviolet B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Antioxidants / pharmacology*
  • Basic Helix-Loop-Helix Transcription Factors / drug effects*
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cells, Cultured
  • Cytoprotection
  • Dose-Response Relationship, Drug
  • Humans
  • Inflammation Mediators / metabolism
  • Interleukin-6 / metabolism
  • Keratinocytes / drug effects*
  • Keratinocytes / enzymology
  • Keratinocytes / radiation effects
  • Lactones / pharmacology*
  • NAD(P)H Dehydrogenase (Quinone) / genetics
  • NAD(P)H Dehydrogenase (Quinone) / metabolism*
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress / drug effects*
  • Oxidative Stress / radiation effects
  • RNA Interference
  • RNA, Messenger / metabolism
  • Receptors, Aryl Hydrocarbon / drug effects*
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism
  • Sesquiterpenes / pharmacology*
  • Signal Transduction / drug effects
  • Transfection
  • Tumor Necrosis Factor-alpha / metabolism
  • Ultraviolet Rays / adverse effects*
  • Up-Regulation

Substances

  • AHR protein, human
  • Antioxidants
  • Basic Helix-Loop-Helix Transcription Factors
  • IL6 protein, human
  • Inflammation Mediators
  • Interleukin-6
  • Lactones
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • RNA, Messenger
  • Receptors, Aryl Hydrocarbon
  • Sesquiterpenes
  • Tumor Necrosis Factor-alpha
  • NAD(P)H Dehydrogenase (Quinone)
  • NQO1 protein, human
  • cynaropicrin