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

• Published in: Toxicology and applied pharmacology 2016-11, Vol.310, p.51-59
• Main Authors: Park, Gunhyuk, Oh, Dal-Seok, Lee, Mi Gi, Lee, Chang Eon, Kim, Yong-ung
• Format: Article
• Language: English
• Subjects: 2,4-Dinitrochlorobenzene; 6-Shogaol; 60 APPLIED LIFE SCIENCES; Allergic dermatitis; Animals; Antiinflammation; Antioxidant; ANTIOXIDANTS; BENZOQUINONES; Catechols - pharmacology; Cell Line; Cytokines - antagonists & inhibitors; DERMATITIS; Dermatitis, Allergic Contact - metabolism; Dermatitis, Allergic Contact - prevention & control; Dinitrochlorobenzene - pharmacology; GLUTATHIONE; HEME; Humans; IN VITRO; IN VIVO; INFLAMMATION; INHIBITION; LYMPHOKINES; Male; MICE; Mice, Inbred ICR; NECROSIS; NEOPLASMS; NF-E2-Related Factor 2 - metabolism; NITRIC OXIDE; Nrf2; OXYGENASES; PHOSPHOTRANSFERASES; REDUCTION; SKIN; THERAPY; THYMUS; Zingiber officinale - chemistry
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2016.08.019

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. [Display omitted] •6-Shogaol inhibited Th2/1-mediated inflammatory mediators in vitro and in vivo.•6-Shogaol regulated ROS/MAPKs/Nrf2 signaling pathway.•6-Shogaol can protect against the development of AD-like skin lesions.