Antioxidant <i>Opuntia ficus-indica</i> 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, Hideo; Kido‐Nakahara, Makiko; Furue, Masutaka

doi:10.1089/jmf.2014.3396

Cited by 46 publications

(61 citation statements)

References 27 publications

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“…Data in the literature shows that most of the phytochemicals upregulate Nrf2 signaling in association with AhR activation [32][33][34]. Besides having an effect on Nrf2, we also noted that S.C. extract has an effect on the AhR pathway.…”

Section: Discussionsupporting

confidence: 65%

Schisandra chinensis Protects the Skin from Global Pollution by Inflammatory and Redox Balance Pathway Modulations: An In Vitro Study

et al. 2018

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Abstract:Epidemiological results show that airborne particulate matter (PM) induces health alterations in line with pulmonary and cardiovascular pathologies. Deleterious effects of PM on the skin have also been investigated. A possible approach to prevent Reactive Oxygen Species (ROS)-mediated disorders for both preventive and treatment means is based on the use of substances, which can be found in plants. These can act as secondary metabolites, and lignans are a promising candidate. Thus, the objective of this study was firstly to identify reconstructed human epidermis, using a transcriptomic approach, and also to identify the effects of Urban Dust and of Urban Dust and Schisandra chinensis (S.C.) extract on the expression of genes that are involved in the response to cellular protection mechanisms. Secondly, we examined the effect of an active extract from S.C. on the protection of human keratinocytes damages that were caused by pollution, through the evaluation of Nrf2 and AhR pathways, NF-kB, and DJ-1. Urban Dust included the over-expression of metalloproteinases MMP-1 and MMP-9 and an increase in Glutathione peroxidase 2 (GPX2). In the presence of Urban Dust, S.C. extract activated the over-expression of several genes that are involved in the antioxidant response and in the detoxification pathway, including Ferritin light chain (FTL) and GPX2. Exposure to urban dust activated the cytoplasmic expression of NF-kB and AhR, when compared to the control. Co-treatment of Urban Dust and S.C. extract increased DJ-1 protein levels, Nrf2 expression, and decreased AhR and NF-kB in the cytoplasm. At the same time, this co-treatment increased SOD2 expression (50%: p < 0.001) and catalase activity (120%: p < 0.05), when compared to Urban Dust alone. Thus, S.C. might be able to protect the Normal Human Epidermal Keratinocytes (NHEK) from environmental aggression, by fighting the harmful effects of urban pollution.

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Section: Discussionsupporting

confidence: 65%

Schisandra chinensis Protects the Skin from Global Pollution by Inflammatory and Redox Balance Pathway Modulations: An In Vitro Study

et al. 2018

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“…In addition to oxidative stress, recent studies have demonstrated that the AHR system mediates antioxidative and protective signaling in response to certain ligands, such as flavonoids, herbal medicines, and azoles [16,18,19,21,31,32,33]. For example, ligation of AHR by ketoconazole induces the nuclear translocation of AHR without producing ROS.…”

Section: Aryl Hydrocarbon Receptor Regulating Both Oxidative and Amentioning

confidence: 99%

“…Various phytochemicals and herbal extracts exert their antioxidant properties by activating the NRF2 system in an AHR-dependent or AHR-independent manner in human epidermal keratinocytes [18,19,20,21,22]. Certain antioxidant phytochemicals also upregulate the expression of filaggrin (FLG), which plays a pivotal role in maintaining epidermal barrier function [19,20,21,23].…”

Section: Introductionmentioning

confidence: 99%

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Antioxidants for Healthy Skin: The Emerging Role of Aryl Hydrocarbon Receptors and Nuclear Factor-Erythroid 2-Related Factor-2

et al. 2017

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Skin is the outermost part of the body and is, thus, inevitably exposed to UV rays and environmental pollutants. Oxidative stress by these hazardous factors accelerates skin aging and induces skin inflammation and carcinogenesis. Aryl hydrocarbon receptors (AHRs) are chemical sensors that are abundantly expressed in epidermal keratinocytes and mediate the production of reactive oxygen species. To neutralize or minimize oxidative stress, the keratinocytes also express nuclear factor-erythroid 2-related factor-2 (NRF2), which is a master switch for antioxidant signaling. Notably, there is fine-tuned crosstalk between AHR and NRF2, which mutually increase or decrease their activation states. Many NRF2-mediated antioxidant phytochemicals are capable of up- and downmodulating AHR signaling. The precise mechanisms by which these phytochemicals differentially affect the AHR and NRF2 system remain largely unknown and warrant future investigation.

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“…Cynaropicrin results in AhR-dependent NRF2 induction, followed by an increased expression of NQO1, and thereby inhibits ROS production mediated by B[ a ]P or UVB, while CYP1A1 mRNA showed a weak increase. Extracts of Opuntia ficus-indica also lead to an albeit weak but nonetheless significant increase in Nrf2 activity and NQO1 expression AhR-dependently and reduction of B[ a ]P- or TNF α -mediated ROS generation [48]. …”

Section: The Ahr-nrf2 Pathwaymentioning

confidence: 99%

Antioxidant Functions of the Aryl Hydrocarbon Receptor

Dietrich

2016

Stem Cells International

121

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The aryl hydrocarbon receptor (AhR) is a transcription factor belonging to the basic helix-loop-helix/PER-ARNT-SIM family. It is activated by a variety of ligands, such as environmental contaminants like polycyclic aromatic hydrocarbons or dioxins, but also by naturally occurring compounds and endogenous ligands. Binding of the ligand leads to dimerization of the AhR with aryl hydrocarbon receptor nuclear translocator (ARNT) and transcriptional activation of several xenobiotic phase I and phase II metabolizing enzymes. It is generally accepted that the toxic responses of polycyclic aromatic hydrocarbons, dioxins, and structurally related compounds are mediated by activation of the AhR. A multitude of studies indicate that the AhR operates beyond xenobiotic metabolism and exerts pleiotropic functions. Increasing evidence points to a protective role of the AhR against carcinogenesis and oxidative stress. Herein, I will highlight data demonstrating a causal role of the AhR in the antioxidant response and present novel findings on potential AhR-mediated antioxidative mechanisms.

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

Cited by 46 publications

References 27 publications

Schisandra chinensis Protects the Skin from Global Pollution by Inflammatory and Redox Balance Pathway Modulations: An In Vitro Study

Schisandra chinensis Protects the Skin from Global Pollution by Inflammatory and Redox Balance Pathway Modulations: An In Vitro Study

Antioxidants for Healthy Skin: The Emerging Role of Aryl Hydrocarbon Receptors and Nuclear Factor-Erythroid 2-Related Factor-2

Antioxidant Functions of the Aryl Hydrocarbon Receptor

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