The Antiaging Activity of Ergothioneine in UVA-Irradiated Human Dermal Fibroblasts via the Inhibition of the AP-1 Pathway and the Activation of Nrf2-Mediated Antioxidant Genes
Open accessAbstract
UVA irradiation induced ROS-mediated photo damage to the human skin leading to coarseness, wrinkling, pigmentation, and cutaneous malignancies. We investigated the dermatoprotective efficacies of submicromolar concentrations of ergothioneine (EGT, 0.125-0.5 μ M), which occurs naturally as a sulfur-containing amino acid, in the mechanisms in human skin fibroblast (HSF) cells. UVA-induced AP-1 (c-Fos and c-Jun) translocation was found to be inhibited by EGT treatments with the parallel inhibition of the collagenolytic matrix metalloproteinase- (MMP-) 1 activation and type I procollagen degradation. Moreover, EGT mitigated UVA-induced ROS generation. An increase in the amount of antioxidant genes (HO-1, NQO-1, and γ -GCLC) from EGT and were associated with upregulated Nrf2 expressions in a dose-dependent or time-dependent manner. We confirmed this from Nrf2 translocation and increased nuclear ARE promoter activity that underlie EGT dermatoprotective activities. Also, glutathione (GSH) levels (from γ -GCLC) were significantly increased. Moreover, we showed that mediated by ERK, JNK, and PKC, signaling cascades mediate Nrf2 translocation. We confirmed this phenomenon by the suppressed nuclear Nrf2 activation in cells that were treated with respective inhibitors (PD98059, SP600125, and GF109203X). However, antioxidant protein expressions were impaired in Nrf2 knockdown cells to confirm that ARE/Nrf2 pathways and the inhibition of AP-1 had significant roles in EGT-mediated protective effects. We can conclude that ergothioneine ameliorated UVA-induced skin aging and is a useful food supplement for skin care products.
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Ergothioneine exhibits anti-aging properties in UVA-irradiated human fibroblast cells through activation of the P13K-AKT pathway.
“Ergothioneine has also been shown to exhibit anti-aging properties in UVA-irradiated human fibroblast cells through activation of the P13K-AKT pathway (Hseu et al. 2020).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Hseu et al. 2020
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Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging
Jomova, K., Raptova, R., Alomar, S. Y., Alwasel, S. H., Nepovimova, E., Kuca, K., & Valko, M. (2023) · Archives of Toxicology · doi:10.1007/s00204-023-03562-9 · Cited by 2,638 · see citing works
- Authors
- Hseu, Y.-C., Vudhya Gowrisankar, Y., Chen, X.-Z., Yang, Y.-C., & Yang, H.-L.
- Affiliations
- Asia University (TW)
- Department of Cosmeceutics, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 40402, Taiwan
- China Medical University (TW)
- Corresponding author
- Yang, Hsin-Ling
- Venue
- Oxidative Medicine and Cellular Longevity
- Publisher
- Wiley
- Published
- 2020-02-12
- Volume
- 2020
- Pages
- 1-13
- ISSN
- 1942-0994 (ISSN-L)
- 1942-0900
- PMC
- PMC7038158
- OpenAlex
- W3005553488
- Cited by
- 81
- References
- 43
- Citations by year
- 2026: 17 · 2025: 13 · 2024: 13 · 2023: 12 · 2022: 10 · 2021: 13 · 2020: 3
- FWCI
- 6.94
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Oxidative Medicine and Cellular Longevity (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Ministry of Education, Ethiopia (CMRC-CHM-8, CMU 107-ASIA-15, CMU101-ASIA-12, CMU 101-ASIA-04, CMU 108-S-04, CMU 107-TU-12, MOST-107-2320-B-039-013-MY3, MOST-106-2320-B-039-054-MY3)
- Chinese Medicine Research Center, China Medical University (CMRC-CHM-8, CMU 107-ASIA-15, CMU101-ASIA-12, CMU 101-ASIA-04, CMU 108-S-04, CMU 107-TU-12, MOST-107-2320-B-039-013-MY3, MOST-106-2320-B-039-054-MY3)
- China Medical University, Taiwan (CMRC-CHM-8, CMU 107-ASIA-15, CMU101-ASIA-12, CMU 101-ASIA-04, CMU 108-S-04, CMU 107-TU-12, MOST-107-2320-B-039-013-MY3, MOST-106-2320-B-039-054-MY3)
- Asia University (CMRC-CHM-8, CMU 107-ASIA-15, CMU101-ASIA-12, CMU 101-ASIA-04, CMU 108-S-04, CMU 107-TU-12, MOST-107-2320-B-039-013-MY3, MOST-106-2320-B-039-054-MY3)
- Ministry of Science and Technology (CMRC-CHM-8, CMU 107-ASIA-15, CMU101-ASIA-12, CMU 101-ASIA-04, CMU 108-S-04, CMU 107-TU-12, MOST-107-2320-B-039-013-MY3, MOST-106-2320-B-039-054-MY3)
- Topics
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Keywords
- ergothioneine, UVA irradiation, skin aging, dermal fibroblasts, AP-1 pathway, Nrf2, antioxidant genes, reactive oxygen species, MMP-1, collagen degradation, heme oxygenase-1, NQO1, gamma-glutamylcysteine synthetase, glutathione, ERK, JNK, protein kinase C
- MeSH terms
- Antioxidants, Cell Line, Ergothioneine, Fibroblasts, Glutathione, Humans, Procollagen, Protein Kinase C, Ultraviolet Rays, Signal Transduction, Skin Aging, Up-Regulation, NAD(P)H Dehydrogenase (Quinone), Reactive Oxygen Species, Transcription Factor AP-1, MAP Kinase Signaling System, RNA, Small Interfering, NF-E2-Related Factor 2, Heme Oxygenase-1
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