Flavonolignan 2,3-dehydrosilydianin activates Nrf2 and upregulates NAD(P)H: quinone oxidoreductase 1 in Hepa1c1c7 cells

Lenka Roubalová, Albena T. Dinkova-Kostova, David Biedermann, Vladimír Křen, Jitka Ulrichová, Jiří Vrba

Research output: Contribution to journalArticle

Abstract

Silybum marianum (milk thistle) is a medicinal plant used for the treatment of various liver disorders. This study examined whether the main flavonolignans from S. marianum (i.e. silybin, silychristin, silydianin) and their 2,3-dehydro derivatives (i.e. 2,3-dehydrosilybin, 2,3-dehydrosilychristin, 2,3-dehydrosilydianin) activate the Nrf2 pathway, which regulates the expression of genes encoding many cytoprotective enzymes, including NAD(P)H:quinone oxidoreductase 1 (NQO1). After 48 h of exposure, 2,3-dehydrosilydianin at concentrations of 25 μM and higher significantly elevated the activity of NQO1 in murine hepatoma Hepa1c1c7 cells. In contrast, other tested compounds at non-cytotoxic concentrations had a mild or negligible effect on the NQO1 activity. Using a luciferase reporter assay, 2,3-dehydrosilydianin was found to significantly activate transcription via the antioxidant response element in stably transfected human AREc32 reporter cells. Moreover, 2,3-dehydrosilydianin caused the accumulation of Nrf2 and significantly induced the expression of the Nqo1 gene at both the mRNA and protein levels in Hepa1c1c7 cells. We found that 2,3-dehydrosilydianin also increased to some extent the expression of other Nrf2 target genes, namely of the heme oxygenase-1 gene (Hmox1) and the glutamate-cysteine ligase modifier subunit gene (Gclm). We conclude that 2,3-dehydrosilydianin activates Nrf2 and induces Nrf2-mediated gene expression in Hepa1c1c7 cells.

Original languageEnglish (US)
Pages (from-to)115-120
Number of pages6
JournalFitoterapia
Volume119
DOIs
StatePublished - Jun 1 2017
Externally publishedYes

Keywords

  • Flavonolignans
  • NQO1
  • Nrf2
  • Silybin
  • Silybum marianum
  • Silymarin

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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  • Cite this

    Roubalová, L., Dinkova-Kostova, A. T., Biedermann, D., Křen, V., Ulrichová, J., & Vrba, J. (2017). Flavonolignan 2,3-dehydrosilydianin activates Nrf2 and upregulates NAD(P)H: quinone oxidoreductase 1 in Hepa1c1c7 cells. Fitoterapia, 119, 115-120. https://doi.org/10.1016/j.fitote.2017.04.012