PMID- 26061570 OWN - NLM STAT- MEDLINE DCOM- 20160713 LR - 20220309 IS - 1557-7600 (Electronic) IS - 1096-620X (Linking) VI - 18 IP - 10 DP - 2015 Oct TI - Antioxidant Opuntia ficus-indica Extract Activates AHR-NRF2 Signaling and Upregulates Filaggrin and Loricrin Expression in Human Keratinocytes. PG - 1143-9 LID - 10.1089/jmf.2014.3396 [doi] AB - 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 alpha or benzo[alpha]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. FAU - Nakahara, Takeshi AU - Nakahara T AD - 1 Division of Skin Surface Sensing, Kyushu University , Fukuoka, Japan . AD - 2 Department of Dermatology, Kyushu University , Fukuoka, Japan . FAU - Mitoma, Chikage AU - Mitoma C AD - 2 Department of Dermatology, Kyushu University , Fukuoka, Japan . AD - 3 Research and Clinical Center for Yusho and Dioxin, Kyushu University , Fukuoka, Japan . FAU - Hashimoto-Hachiya, Akiko AU - Hashimoto-Hachiya A AD - 2 Department of Dermatology, Kyushu University , Fukuoka, Japan . FAU - Takahara, Masakazu AU - Takahara M AD - 2 Department of Dermatology, Kyushu University , Fukuoka, Japan . FAU - Tsuji, Gaku AU - Tsuji G AD - 2 Department of Dermatology, Kyushu University , Fukuoka, Japan . FAU - Uchi, Hiroshi AU - Uchi H AD - 2 Department of Dermatology, Kyushu University , Fukuoka, Japan . AD - 3 Research and Clinical Center for Yusho and Dioxin, Kyushu University , Fukuoka, Japan . FAU - Yan, Xianghong AU - Yan X AD - 4 P&G Innovation Godo Kaisha , Kobe, Japan . FAU - Hachisuka, Junichi AU - Hachisuka J AD - 2 Department of Dermatology, Kyushu University , Fukuoka, Japan . FAU - Chiba, Takahito AU - Chiba T AD - 2 Department of Dermatology, Kyushu University , Fukuoka, Japan . FAU - Esaki, Hitokazu AU - Esaki H AD - 2 Department of Dermatology, Kyushu University , Fukuoka, Japan . FAU - Kido-Nakahara, Makiko AU - Kido-Nakahara M AD - 2 Department of Dermatology, Kyushu University , Fukuoka, Japan . FAU - Furue, Masutaka AU - Furue M AD - 1 Division of Skin Surface Sensing, Kyushu University , Fukuoka, Japan . AD - 2 Department of Dermatology, Kyushu University , Fukuoka, Japan . AD - 3 Research and Clinical Center for Yusho and Dioxin, Kyushu University , Fukuoka, Japan . LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150518 PL - United States TA - J Med Food JT - Journal of medicinal food JID - 9812512 RN - 0 (Antioxidants) RN - 0 (FLG protein, human) RN - 0 (Filaggrin Proteins) RN - 0 (Intermediate Filament Proteins) RN - 0 (Membrane Proteins) RN - 0 (NF-E2-Related Factor 2) RN - 0 (NFE2L2 protein, human) RN - 0 (Plant Extracts) RN - 0 (Receptors, Aryl Hydrocarbon) RN - 0 (loricrin) RN - EC 1.6.5.2 (NAD(P)H Dehydrogenase (Quinone)) RN - EC 1.6.5.2 (NQO1 protein, human) SB - IM MH - Antioxidants/pharmacology MH - Cells, Cultured MH - Filaggrin Proteins MH - Gene Expression/drug effects MH - Gene Knockdown Techniques MH - Humans MH - Intermediate Filament Proteins/*analysis MH - Keratinocytes/chemistry/*drug effects/metabolism MH - Membrane Proteins/*analysis MH - NAD(P)H Dehydrogenase (Quinone)/metabolism MH - NF-E2-Related Factor 2/deficiency/genetics/*physiology MH - Opuntia/*chemistry MH - Plant Extracts/pharmacology MH - Receptors, Aryl Hydrocarbon/drug effects/*metabolism MH - Signal Transduction/drug effects MH - Skin Diseases/drug therapy OTO - NOTNLM OT - NQO1 OT - NRF2 OT - Opuntia ficus-indica extract OT - antioxidant OT - aryl hydrocarbon receptor OT - filaggrin EDAT- 2015/06/11 06:00 MHDA- 2016/07/14 06:00 CRDT- 2015/06/11 06:00 PHST- 2015/06/11 06:00 [entrez] PHST- 2015/06/11 06:00 [pubmed] PHST- 2016/07/14 06:00 [medline] AID - 10.1089/jmf.2014.3396 [doi] PST - ppublish SO - J Med Food. 2015 Oct;18(10):1143-9. doi: 10.1089/jmf.2014.3396. Epub 2015 May 18.