Antioxidant Opuntia ficus-indica Extract Activates AHR-NRF2 Signaling and Upregulates Filaggrin and Loricrin Expression in Human Keratinocytes

Takeshi Nakahara, Chikage Mitoma, Akiko Hashimoto-Hachiya, Masakazu Takahara, Gaku Tsuji, Hiroshi Uchi, Xianghong Yan, Junichi Hachisuka, Takahito Chiba, Hitokazu Esaki, Makiko Kido-Nakahara, Masutaka Furue

Research output: Contribution to journalArticle

21 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)1143-1149
Number of pages7
JournalJournal of medicinal food
Volume18
Issue number10
DOIs
Publication statusPublished - Oct 1 2015

Fingerprint

Opuntia
Aryl Hydrocarbon Receptors
Keratinocytes
Up-Regulation
Antioxidants
Cactaceae
Hypoglycemic Agents
NAD
Ligation
Reactive Oxygen Species
Oxidoreductases
Oxidative Stress
Anti-Inflammatory Agents
Down-Regulation
Animal Models
Tumor Necrosis Factor-alpha
filaggrin
loricrin
Cytokines
Skin

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

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.

In: Journal of medicinal food, Vol. 18, No. 10, 01.10.2015, p. 1143-1149.

Research output: Contribution to journalArticle

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. / Antioxidant Opuntia ficus-indica Extract Activates AHR-NRF2 Signaling and Upregulates Filaggrin and Loricrin Expression in Human Keratinocytes. In: Journal of medicinal food. 2015 ; Vol. 18, No. 10. pp. 1143-1149.
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