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

Autor: Lenka, Roubalová, Albena T, Dinkova-Kostova, David, Biedermann, Vladimír, Křen, Jitka, Ulrichová, Jiří, Vrba
Rok vydání: 2017
Předmět:
NF-E2-Related Factor 2
Glutamate-Cysteine Ligase
NQO1
NAD(P)H:quinone oxidoreductase 1
Gene Expression
ARE
antioxidant response element
Gapdh
glyceraldehyde-3-phosphate dehydrogenase
DMSO
dimethyl sulfoxide
SC
silychristin
Article
Nrf2
DHSD
2
3-dehydrosilydianin
SB
silybin
Mice
MTT
3-(4
5-dimethylthiazol-2-yl)-2
5-diphenyltetrazolium bromide
Silybum marianum
ROS
reactive oxygen species
Cell Line
Tumor
NAD(P)H Dehydrogenase (Quinone)
Nrf2/NFE2L2
NF-E2 p45-related factor 2
Animals
Humans
Milk Thistle
DHSC
2
3-dehydrosilychristin
SFN
sulforaphane
Molecular Structure
HMOX1
heme oxygenase-1
Membrane Proteins
SD
silydianin
GCLM
glutamate-cysteine ligase modifier subunit
Up-Regulation
Keap1
Kelch-like ECH-associated protein 1
Flavonolignans
Silybin
NQO1
DHSB
2
3-dehydrosilybin
Heme Oxygenase-1
GCLC
glutamate-cysteine ligase catalytic subunit
Silymarin
Zdroj: Fitoterapia
ISSN: 1873-6971
Popis: 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.
Graphical abstract Image 1
Databáze: OpenAIRE
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