Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Mar 3;9(3):223.
doi: 10.3390/nu9030223.

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

Masutaka Furue  1   2   3 , Hiroshi Uchi  4 , Chikage Mitoma  5   6 , Akiko Hashimoto-Hachiya  7 , Takahito Chiba  8 , Takamichi Ito  9 , Takeshi Nakahara  10   11 , Gaku Tsuji  12   13
Affiliations
Review

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

Masutaka Furue et al. Nutrients. .

Abstract

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.

Keywords: antioxidants; aryl hydrocarbon receptor; nuclear factor-erythroid 2-related factor-2; phytochemicals; reactive oxygen species.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Activation of AHR. In untreated normal human keratinocytes, AHR (red) is mainly located in the cytoplasm (A1). Nuclei are stained with 4′,6-diamidino-2-phenylindole (blue, A2). In the presence of soybean tar glyteer, AHR is translocated from the cytoplasm to the nucleus (B1, red). Nuclei are stained with 4′,6-diamidino-2-phenylindole (blue, B2).
Figure 2
Figure 2
Activation of NRF2. In untreated normal human keratinocytes, NRF2 (green) is mainly located in the cytoplasm (A); Opuntia ficus-indica extract activates NRF2 and induces its cytoplasmic to nuclear translocation (B).
Figure 3
Figure 3
Antioxidant phytochemicals differentially modulate aryl hydrocarbon receptor (AHR), cytochrome P450 1A1 (CYP1A1) and nuclear factor-erythroid 2-related factor-2 (NRF2). Oxidative ligands, such as ultraviolet radiation, dioxins, and environmental polycyclic pollutants, activate the AHR and CYP1A1 system, which generates reactive oxygen species (ROS) and causes DNA damage and inflammation. Antioxidant phytochemicals exert their antioxidant capacity by activating NRF2, which is a master transcription factor for the induction of antioxidant enzymes such as NAD(P)H: quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1). These antioxidant enzymes neutralize or minimize ROS production. Antioxidant phytochemicals are categorized into at least three groups based on their capacity for up- and downmodulating AHR and CYP1A1. Group 1 contains NRF2 agonists with AHR agonistic activity (①). Group 2 contains NRF2 agonists with AHR antagonistic activity (②). Group 3 contains NRF2 agonists with CYP1A1 inhibitor activity (③).
Figure 4
Figure 4
Antioxidant activity of Opuntia ficus-indica extract (OFE). Reactive oxygen species (ROS) are visualized with dichloro-dihydro-fluorescein diacetate staining (green). The production of ROS is not active in the untreated or OFE-treated human keratinocytes. Tumor necrosis factor α (TNFα) induces ROS production, which is significantly inhibited by OFE (TNFα + OFE).
Figure 5
Figure 5
Synergistic antioxidant activity of Galactomyces ferment filtrate (GFF; 0.1%) and epigallocatechin gallate (EGCG; 10 μM). Reactive oxygen species (ROS) are visualized with dichloro-dihydro-fluorescein diacetate staining (green). The production of ROS is very slight in the human keratinocytes treated with medium control (untreated), a low concentration of GFF, or a low concentration of EGCG. Tumor necrosis factor α (TNFα) induces ROS production, which is weakly inhibited by a low concentration of either GFF (TNFα + GFF) or EGCG (TNFα + EGCG). The ROS production by TNFα is markedly downregulated by the simultaneous addition of GFF and EGCG (TNFα + GFF + EGCG).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Kruk J., Duchnik E. Oxidative stress and skin diseases: Possible role of physical activity. Asian Pac. J. Cancer Prev. 2014;15:561–568. doi: 10.7314/APJCP.2014.15.2.561. - DOI - PubMed
    1. Furue M., Kadono T. Nonsegmental vitiligo update. Dermatol. Sin. 2016;34:173–176. doi: 10.1016/j.dsi.2016.07.001. - DOI
    1. Ji H., Li X.K. Oxidative stress in atopic dermatitis. Oxid. Med. Cell. Longev. 2016;2016:2721469. doi: 10.1155/2016/2721469. - DOI - PMC - PubMed
    1. Prie B.E., Voiculescu V.M., Ionescu-Bozdog O.B., Petrutescu B., Iosif L., Gaman L.E., Clatici V.G., Stoian I., Giurcaneanu C. Oxidative stress and alopecia areata. J. Med. Life. 2015;8:43–46. - PMC - PubMed
    1. Katta R., Brown D.N. Diet and skin cancer: The potential role of dietary antioxidants in nonmelanoma skin cancer prevention. J. Skin Cancer. 2015;2015:893149. doi: 10.1155/2015/893149. - DOI - PMC - PubMed

MeSH terms

LinkOut - more resources

-