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Redox Biol. 2019 Sep 3;28:101317. doi: 10.1016/j.redox.2019.101317. [Epub ahead of print]

The dietary triterpenoid 18α-Glycyrrhetinic acid protects from MMC-induced genotoxicity through the ERK/Nrf2 pathway.

Author information

1
Institute of Chemical Biology, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, 116 35, Athens, Greece. Electronic address: lefakimaria@yahoo.gr.
2
Institute of Chemical Biology, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, 116 35, Athens, Greece; Institute of Nutritional Sciences, Nutrigenomics Section, Friedrich Schiller University of Jena, Dornburger Straße 29, 07743, Jena, Germany. Electronic address: npapaevgeniou@eie.gr.
3
Research Group on Nutrition and Oxidative Stress, Guillem Colom Bldg, Campus, University of Balearic Islands & CIBEROBN (Physiopahotology of Obesity and Nutrition), E-07122, Palma de Mallorca, Balearic Islands, Spain. Electronic address: pep.tur@uib.es.
4
Section of Biochemistry and Molecular Biology, Department of Biology, National and Kapodistrian University of Athens, Zografou Campus, 15701, Athens, Greece. Electronic address: cvorgias@biol.uoa.gr.
5
Service of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital, 1011, Lausanne, Switzerland. Electronic address: gerasimos.sykiotis@chuv.ch.
6
Institute of Chemical Biology, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, 116 35, Athens, Greece. Electronic address: nikichon@eie.gr.

Abstract

18α-Glycyrrhetinic acid (18α-GA) is a bioactive triterpenoid that has been shown to activate the nuclear factor (erythroid-derived-2)-like 2 (Nrf2), the main transcription factor that orchestrates the cellular antioxidant response, in both cellular and organismal context. Although various beneficial properties of 18α-GA have been revealed, including its anti-oxidation and anti-aging activity, its possible protective effect against DNA damage has never been addressed. In this study, we investigated the potential beneficial properties of 18α-GA against DNA damage induced by mitomycin C (MMC) treatment. Using human primary fibroblasts exposed to MMC following pre-treatment with 18α-GA, we reveal an Nrf2-mediated protective effect against MMC-induced cell death that depends on extracellular signal-regulated kinase (ERK) signaling. In total, our results reveal an additional beneficial effect of the Nrf2 activator 18α-GA, suggesting that this important phytochemical compound is a potential candidate in preventive and/or therapeutic schemes against conditions (such as aging) or diseases that are characterized by both oxidative stress and DNA damage.

KEYWORDS:

18α–Glycyrrhetinic acid; DNA damage; ERK pathway; Mitomycin C; Nrf2; Phytochemicals

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