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KMID : 1161420150180101143
Journal of Medicinal Food
2015 Volume.18 No. 10 p.1143 ~ p.1149
Antioxidant Opuntia ficus-indica Extract Activates AHR-NRF2 Signaling and Upregulates Filaggrin and Loricrin Expression in Human Keratinocytes
Nakahara Takeshi

Mitoma Chikage
Hashimoto-Hachiya Akiko
Takahara Masakazu
Tsuji Gaku
Uchi Hiroshi
Yan Xianghong
Hachisuka Junichi
Chiba Takahito
Esaki Hitokazu
Kido-Nakahara Makiko
Furue Masutaka
Abstract
Opuntia ficus-indica (OFI) is a cactus species widely used as an anti-inflammatory, antilipidemic, and hypoglycemic agent. It has been shown that OFI extract (OFIE) inhibits oxidative stress in animal models of diabetes and hepatic disease; however, its antioxidant mechanism remains largely unknown. In this study, we demonstrated that OFIE exhibited potent antioxidant activity through the activation of nuclear factor erythroid 2-related factor 2 (NRF2) and the downstream antioxidant enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1), which inhibited the generation of reactive oxygen species in keratinocytes challenged with tumor necrosis factor ¥á or benzo[¥á]pyrene. The antioxidant capacity of OFIE was canceled in NRF2 knockdown keratinocytes. OFIE exerted this NRF2-NQO1 upregulation through activation of the aryl hydrocarbon receptor (AHR). Moreover, the ligation of AHR by OFIE upregulated the expression of epidermal barrier proteins: filaggrin and loricrin. OFIE also prevented TH2 cytokine-mediated downregulation of filaggrin and loricrin expression in an AHR-dependent manner because it was canceled in AHR knockdown keratinocytes. Antioxidant OFIE is a potent activator of AHR-NRF2-NQO1 signaling and may be beneficial in treating barrier-disrupted skin disorders.
KEYWORD
antioxidant, aryl hydrocarbon receptor, filaggrin, Opuntia ficus-indica extract, NRF2, NQO1
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