Combination of dimethylmethoxy chromanol and turmeric root extract synergically attenuates ultraviolet-induced oxidative damage by increasing endogenous antioxidants in HaCaT cells.

Publisher: Blackwell Country of Publication: England NLM ID: 9504453 Publication Model: Print Cited Medium: Internet ISSN: 1600-0846 (Electronic) Linking ISSN: 0909752X NLM ISO Abbreviation: Skin Res Technol Subsets: MEDLINE

Publication: <1998-> : Oxford : Blackwell
Original Publication: Copenhagen, Denmark ; Cambridge, MA : Munksgaard, c1995-

Antioxidants*/pharmacology ; Antioxidants*/therapeutic use ; Antioxidants*/chemistry ; HaCaT Cells*; Humans ; Oxidative Stress ; Reactive Oxygen Species ; Superoxide Dismutase/metabolism ; Superoxide Dismutase/pharmacology ; Ultraviolet Rays/adverse effects ; Keratinocytes/metabolism

Background: Repeated exposure to UV generates excessive reactive oxygen species (ROS) and damages the enzymatic antioxidant defense system including quinone oxidoreductase 1 (NQO1) and superoxide dismutase (SOD) in skin. Topical application of antioxidants may prevent the undesired damage of cellular proteins, lipids and DNA in skin. Dimethylmethoxy chromanol (DMC) is a bioinspired molecule, designed to be a structural analog to the γ-tocopherol that is naturally present in vegetables and plants. Turmeric root extract (TRE) is from a plant in South Asia extensively used as a food spice & vegetable, and its main components are turmerones. As both DMC and TRE are strong antioxidants with complementary antioxidation mechanisms, the aim of this study was to investigate the enhanced protective effects of their combination on oxidative damage in HaCaT cells following UVB exposure.
Materials and Methods: The effects of single and combined administrations of DMC and TRE on the SOD activity of HaCaT cells were evaluated by the SOD assay and qPCR. The NQO1 expression in the UVB-treated HaCaT cells was analyzed by the Western Blot. Furthermore, a clinical test involving 24 subjects was conducted to evaluate the in vivo antioxidation efficacies of the serum formulated with the combination of DMC and TRE at the optimal weight ratio.
Results: SOD assay showed that pretreating DMC or TRE alone could not preserve the impaired HaCaT SOD activity after UVB treatment. DMC and TRE at 1:1 weight ratio was the optimal combination to enhance the HaCaT SOD activity by approximately more than 1-fold compared with either of the single treated groups. No enhancement effect was observed at other mixing ratios. The 1:1 weight ratio was further proved to be optimal as this combination boosted the NQO1 expression by more than 50%, whereas no boosting effect was observed at other mixing ratios. The clinical test of the serum containing this optimal antioxidant combination demonstrated promising in vivo antioxidation efficacies after 4-week use, including 7.16% improvement in skin lightening, 18.29% reduction in skin redness, 35.68% decrease in TEWL, 19.05% increase in skin gloss and 32.04% enhancement in skin firmness.
Conclusion: Collectively, our results indicated that the combination of DMC and TRE at 1:1 weight ratio attenuated the UV-induced oxidative damage by synergistically boosting endogenous antioxidant enzyme activity in HaCaT cells. Therefore, this optimal antioxidant combination is a promising treatment to boost skin antioxidation defense system.
(© 2023 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.)

Adwas AA, Elsayed ASI, Azab AE, Quwaydir FA. Oxidative stress and antioxidant mechanisms in human body. J Appl Biotechnol Bioeng. 2019;6:43-47.
Ge G, Wang Y, Xu Y, et al. Induced skin aging by blue-light irradiation in human skin fibroblasts via TGF-β, JNK and EGFR pathways. J Dermatol Sci. 2023;111:52-59.
Papaccio F, D Arino A, Caputo S, Bellei B. Focus on the contribution of oxidative stress in skin aging. Antioxidants (Basel). 2022;11:1121.
Salminen A, Kaarniranta K, Kauppinen A. Photoaging: UV radiation-induced inflammation and immunosuppression accelerate the aging process in the skin. Inflamm Res. 2022;71:817-831.
Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB. Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal. 2014;20:1126-1167.
Kruk J, Duchnik E. Oxidative stress and skin diseases: possible role of physical activity. Asian Pac J Cancer Prev. 2014;15:561-568.
Snezhkina AV, Kudryavtseva AV, Kardymon OL, et al. ROS generation and antioxidant defense systems in normal and malignant cells. Oxid Med Cell Longev. 2019;2019:6175804.
Mirończuk-Chodakowska I, Witkowska AM, Zujko ME. Endogenous non-enzymatic antioxidants in the human body. Adv Med Sci. 2018;63:68-78.
Altobelli GG, Van Noorden S, Balato A, Cimini V. Copper/zinc superoxide dismutase in human skin: current knowledge. Front Med (Lausanne). 2020;7:183.
Ighodaro OM, Akinloye OA. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): their fundamental role in the entire antioxidant defence grid. Alexandria J Med. 2018;54:287-293.
Juan CA, Pérez de la Lastra JM, Plou FJ, Pérez-Lebeña E. The chemistry of reactive oxygen species (ROS) revisited: outlining their role in biological macromolecules (DNA, lipids and proteins) and induced pathologies. Int J Mol Sci. 2021;22:4642.
Le Gal K, Schmidt EE, Sayin VI. Cellular redox homeostasis. Antioxidants (Basel). 2021;10:1377.
Vomund S, Schäfer A, Parnham MJ. Brüne B, von Knethen A. Nrf2, the master regulator of anti-oxidative responses. Int J Mol Sci. 2017;18:2772.
He F, Antonucci L, Karin M. NRF2 as a regulator of cell metabolism and inflammation in cancer. Carcinogenesis. 2020;41:405-416.
Younus H. Therapeutic potentials of superoxide dismutase. Int J Health Sci (Qassim). 2018;12:88-93.
Perry JJ, Shin DS, Getzoff ED, Tainer JA. The structural biochemistry of the superoxide dismutases. Biochim Biophys Acta. 2010;1804:245-262.
Che M, Wang R, Li X, Wang HY, Zheng XFS. Expanding roles of superoxide dismutases in cell regulation and cancer. Drug Discov Today. 2016; 21:143-149.
Burke R, Chu C, Zhou GD, et al. Role of human NADPH quinone oxidoreductase (NQO1) in oxygen-mediated cellular injury and oxidative DNA damage in human pulmonary cells. Oxid Med Cell Longev. 2021;2021:5544600.
Igarashi O, Yonekawa Y, Fujiyama-Fujihara Y. Synergistic action of vitamin E and vitamin C in vivo using a new mutant of Wistar-strain rats, ODS, unable to synthesize vitamin C. J Nutr Sci Vitaminol (Tokyo). 1991;37:359-369.
Traber MG, Stevens JF. Vitamins C and E: beneficial effects from a mechanistic perspective. Free Radic Biol Med. 2011;51:1000-1013.
Sotler R, Poljšak B, Dahmane R, et al. Prooxidant activities of antioxidants and their impact on health. Acta Clin Croat. 2019;58:726-736.
Kaźmierczak-Barańska J, Boguszewska K, Adamus-Grabicka A, Karwowski BT. Two faces of vitamin c-antioxidative and pro-oxidative agent. Nutrients. 2020;12:1501-1519.
Le Quéré S, Lacan D, Lemaire B, Carillon J, Schmitt K. The role of superoxide dismutase (SOD) in skin disorders. Nutrafoods. 2014;13:13-27.
Lin TK, Zhong L, Santiago JL. Anti-inflammatory and skin barrier repair effects of topical application of some plant oils. Int J Mol Sci. 2017;19:70-90.
Lee MJ, Agrahari G, Kim HY, et al. Extracellular superoxide dismutase prevents skin aging by promoting collagen production through the activation of ampk and nrf2/ho-1 cascades. J Invest Dermatol. 2021;141:2344-2353.

Keywords: NQO1; SOD; dimethylmethoxy chromanol; endogenous antioxidants; synergistically; turmeric root extract

0 (Antioxidants)
950-99-2 (2,2,5,7,8-pentamethyl-1-hydroxychroman)
856YO1Z64F (turmeric extract)
0 (Reactive Oxygen Species)
EC 1.15.1.1 (Superoxide Dismutase)

Date Created: 20231220 Date Completed: 20231221 Latest Revision: 20231228

20231228

PMC10730978

10.1111/srt.13539

38115632