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Oxid Med Cell Longev. 2019 Nov 14;2019:4098674. doi: 10.1155/2019/4098674. eCollection 2019.

Zerumbone Exhibits Antiphotoaging and Dermatoprotective Properties in Ultraviolet A-Irradiated Human Skin Fibroblast Cells via the Activation of Nrf2/ARE Defensive Pathway.

Hseu YC1,2,3,4,5, Chang CT1, Gowrisankar YV1, Chen XZ1, Lin HC6, Yen HR3,4,5,7,8,9, Yang HL10.

Author information

1
Department of Cosmeceutics, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 40402, Taiwan.
2
Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan.
3
Chinese Medicine Research Center, China Medical University, Taichung 40402, Taiwan.
4
Research Center of Chinese Herbal Medicine, China Medical University, Taichung 40402, Taiwan.
5
Department of Biotechnology, Asia University, Taichung 41354, Taiwan.
6
School of Pharmacy, China Medical University, Taichung 40402, Taiwan.
7
Department of Chinese Medicine, China Medical University Hospital, Taichung 404, Taiwan.
8
Research Center for Traditional Chinese Medicine, Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan.
9
School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan.
10
Institute of Nutrition, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 40402, Taiwan.

Abstract

Ultraviolet A (UVA) irradiation (320-400 nm range) triggers deleterious consequences in skin cell microenvironment leading to skin damage, photoaging (premature skin aging), and cancer. The accumulation of intracellular reactive oxygen species (ROS) plays a key role in this effect. With rapid progress in cosmetic health and quality of life, use of safe and highly effective phytochemicals has become a need of the hour. Zerumbone (ZER), a natural sesquiterpene, from Zingiber zerumbet rhizomes is well-known for its beneficial effects. We investigated the antiphotoaging and dermatoprotective efficacies of ZER (2-8 μM) against UVA irradiation (3 J/cm2) and elucidated the underlying molecular mechanisms in human skin fibroblast (HSF) cells. ZER treatment prior to low dose of UVA exposure increased cell viability. UVA-induced ROS generation was remarkably suppressed by ZER with parallel inhibition of MMP-1 activation and collagen III degradation. This was due to the inhibition of AP-1 (c-Fos and c-Jun) translocation. Furthermore, ZER alleviated UVA-induced SA-β-galactosidase activity. Dose- or time-dependent increase of antioxidant genes, HO-1 and γ-GCLC by ZER, was associated with increased expression and nuclear accumulation of Nrf2 as well as decreased cytosolic Keap-1 expressions. Altered luciferase activity of ARE could explain the significance of Nrf2/ARE pathway underlying the dermatoprotective properties of ZER. Pharmacological inhibition of various signaling pathways suppressed nuclear Nrf2 activation in HSF cells confirming that Nrf2 translocation was mediated by ERK, JNK, PI3K/AKT, PKC, AMPK, casein kinase II, and ROS signaling pathways. Moreover, increased basal ROS levels and Nrf2 translocation seem crucial in ZER-mediated Nrf2/ARE signaling pathway. This was also evidenced from Nrf2 knocked-out studies in which ZER was not able to suppress the UVA-induced ROS generation in the absence of Nrf2. This study concluded that in the treatment of UVA-induced premature skin aging, ZER may consider as a desirable food supplement for skin protection and/or preparation of skin care products.

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