title: Antioxidant Opuntia ficus-indica Extract Activates AHR-NRF2 Signaling and Upregulates Filaggrin and Loricrin Expression in Human Keratinocytes.
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
  quinone oxidoreductase 1 (NQO1), which inhibited the generation of reactive oxygen species in keratinocytes challenged with tumor necrosis factor α or benzo[α]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.
authors.affiliation: 1 Division of Skin Surface Sensing, Kyushu University , Fukuoka, Japan .|2 Department of Dermatology, Kyushu University , Fukuoka, Japan .
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakahara
authors.affiliation: 2 Department of Dermatology, Kyushu University , Fukuoka, Japan .|3 Research and Clinical Center for Yusho and Dioxin, Kyushu University , Fukuoka, Japan .
authors.forename: Chikage
authors.initials: C
authors.lastname: Mitoma
authors.affiliation: 2 Department of Dermatology, Kyushu University , Fukuoka, Japan .
authors.forename: Akiko
authors.initials: A
authors.lastname: Hashimoto-Hachiya
authors.affiliation: 2 Department of Dermatology, Kyushu University , Fukuoka, Japan .
authors.forename: Masakazu
authors.initials: M
authors.lastname: Takahara
authors.affiliation: 2 Department of Dermatology, Kyushu University , Fukuoka, Japan .
authors.forename: Gaku
authors.initials: G
authors.lastname: Tsuji
authors.affiliation: 2 Department of Dermatology, Kyushu University , Fukuoka, Japan .|3 Research and Clinical Center for Yusho and Dioxin, Kyushu University , Fukuoka, Japan .
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uchi
authors.affiliation: 4 P&G Innovation Godo Kaisha , Kobe, Japan .
authors.forename: Xianghong
authors.initials: X
authors.lastname: Yan
authors.affiliation: 2 Department of Dermatology, Kyushu University , Fukuoka, Japan .
authors.forename: Junichi
authors.initials: J
authors.lastname: Hachisuka
authors.affiliation: 2 Department of Dermatology, Kyushu University , Fukuoka, Japan .
authors.forename: Takahito
authors.initials: T
authors.lastname: Chiba
authors.affiliation: 2 Department of Dermatology, Kyushu University , Fukuoka, Japan .
authors.forename: Hitokazu
authors.initials: H
authors.lastname: Esaki
authors.affiliation: 2 Department of Dermatology, Kyushu University , Fukuoka, Japan .
authors.forename: Makiko
authors.initials: M
authors.lastname: Kido-Nakahara
authors.affiliation: 1 Division of Skin Surface Sensing, Kyushu University , Fukuoka, Japan .|2 Department of Dermatology, Kyushu University , Fukuoka, Japan .|3 Research and Clinical Center for Yusho and Dioxin, Kyushu University , Fukuoka, Japan .
authors.forename: Masutaka
authors.initials: M
authors.lastname: Furue
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D002478:Cells, Cultured; D000091344:Filaggrin Proteins; D015870:Gene Expression / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D007381:Intermediate Filament Proteins / Q000032:analysis*; D015603:Keratinocytes / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D008565:Membrane Proteins / Q000032:analysis*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D029747:Opuntia / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D012871:Skin Diseases / Q000188:drug therapy
chemical_list: D000975:Antioxidants; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D010936:Plant Extracts; D018336:Receptors, Aryl Hydrocarbon; C064554:loricrin; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human
keywords: NQO1; NRF2; Opuntia ficus-indica extract; antioxidant; aryl hydrocarbon receptor; filaggrin