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 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.
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AHR-targeting antioxidant phytochemicals or antioxidant medicinal chemicals do not generate appreciable amounts of reactive oxygen species, probably due to efficient induction of antioxidant enzymes mediated by NRF2 activation.
“Notably, the AHR-targeting antioxidant phytochemicals or antioxidant medicinal chemicals do not generate appreciable amounts of reactive oxygen species probably due to efficient induction of antioxidant enzymes mediated by NRF2 activation [19,20,21,27].”
From Antioxidant Artemisia princeps Extract Enhances the Expression of Filaggrin and Loricrin via the AHR/OVOL1 Pathway (2017) · cites this paper as [21]
Some antioxidant phytochemicals such as soybean tar and Opuntia ficus-indica extract activate NRF2 via the AHR pathway.
“Some antioxidant phytochemicals such as soybean tar and Opuntia ficus-indica extract activate NRF2 via AHR pathway [14,19,21].”
From Antioxidant Artemisia princeps Extract Enhances the Expression of Filaggrin and Loricrin via the AHR/OVOL1 Pathway (2017) · cites this paper as [21]
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- Authors
- Nakahara, T., Mitoma, C., Hashimoto-Hachiya, A., Takahara, M., Tsuji, G., Uchi, H., Yan, X., Hachisuka, J., Chiba, T., Esaki, H., Kido-Nakahara, M., & Furue, M.
- Affiliations
- Kyushu University (JP)
- Department of Dermatology, Kyushu University, Fukuoka, Japan.
- P&G Innovation Godo Kaisha, Kobe, Japan.
- Corresponding author
- Furue, Masutaka
- ORCID
- Venue
- Journal of Medicinal Food
- Publisher
- SAGE Publications
- Published
- 2015-10
- Volume
- 18
- Issue
- 10
- Pages
- 1143-1149
- ISSN
- 1096-620X (ISSN-L)
- 1557-7600
- OpenAlex
- W2152644597
- Cited by
- 49
- References
- 26
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 4 · 2022: 9 · 2021: 4 · 2020: 5 · 2019: 9 · 2018: 4 · 2017: 5 · 2016: 4 · 2015: 1
- FWCI
- 2.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Medicinal Food (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Life Sciences › Agricultural and Biological Sciences › Food Science › Botanical Research and Applications
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Keywords
- Opuntia ficus-indica, cactus extract, aryl hydrocarbon receptor, Nrf2 signaling, NQO1, keratinocytes, filaggrin, loricrin, skin barrier, Th2 cytokines, oxidative stress, reactive oxygen species, benzo[a]pyrene, TNF-α, antioxidant activity
- MeSH terms
- Filaggrin Proteins, Antioxidants, Cells, Cultured, Humans, Intermediate Filament Proteins, Membrane Proteins, Plant Extracts, Skin Diseases, Signal Transduction, Keratinocytes, Gene Expression, NAD(P)H Dehydrogenase (Quinone), Receptors, Aryl Hydrocarbon, Opuntia, NF-E2-Related Factor 2, Gene Knockdown Techniques
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