6-Shogaol, an active compound of ginger, alleviates allergic dermatitis-like skin lesions via cytokine inhibition by activating the Nrf2 pathway

Toxicol Appl Pharmacol. 2016 Nov 1;310:51-59. doi: 10.1016/j.taap.2016.08.019. Epub 2016 Aug 22.

Abstract

Allergic dermatitis (AD) clinically presents with skin erythematous plaques, eruption, and elevated serum IgE, and T helper cell type 2 and 1 (Th2 and Th1) cytokine levels. 6-Shogaol [1-(4-hydroxy-methoxyphenyl)-4-decen-one], a pungent compound isolated from ginger, has shown anti-inflammatory effects, but its inhibitory effects on AD are unknown. The aim of this study was to examine whether 6-shogaol inhibits AD-like skin lesions and their underlying mechanism in vivo and in vitro. An AD-like response was induced by tumor necrosis factor-α (TNF-α)+IFN-γ in human keratinocytes or by 2,4-dinitrochlorobenzene (DNCB) in mice. In vivo, 6-shogaol inhibited the development of DNCB-induced AD-like skin lesions and scratching behavior, and showed significant reduction in Th2/1-mediated inflammatory cytokines, IgE, TNF-α, IFN-γ, thymus and activation-regulated chemokine, IL-1, 4, 12, and 13, cyclooxygenase-2, and nitric oxide synthase levels. In vitro, 6-shogaol inhibited reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPKs) signaling, and increased the levels of total glutathione, heme oxygenase-1, and quinone 1 via nuclear factor erythroid 2 related factor 2 (Nrf2) activation. 6-Shogaol can alleviate AD-like skin lesions by inhibiting immune mediators via regulating the ROS/MAPKs/Nrf2 signaling pathway, and may be an effective alternative therapy for AD.

Keywords: 2,4-Dinitrochlorobenzene; 6-Shogaol; Allergic dermatitis; Antiinflammation; Antioxidant; Nrf2.

MeSH terms

  • Animals
  • Catechols / pharmacology*
  • Cell Line
  • Cytokines / antagonists & inhibitors*
  • Dermatitis, Allergic Contact / metabolism
  • Dermatitis, Allergic Contact / prevention & control*
  • Dinitrochlorobenzene / pharmacology
  • Ginger / chemistry*
  • Humans
  • Male
  • Mice
  • Mice, Inbred ICR
  • NF-E2-Related Factor 2 / metabolism*

Substances

  • Catechols
  • Cytokines
  • Dinitrochlorobenzene
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • shogaol