Flavonolignan 2,3-dehydrosilydianin activates Nrf2 and upregulates NAD(P)H:quinone oxidoreductase 1 in Hepa1c1c7 cells
| العنوان: | Flavonolignan 2,3-dehydrosilydianin activates Nrf2 and upregulates NAD(P)H:quinone oxidoreductase 1 in Hepa1c1c7 cells |
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| المؤلفون: | Lenka, Roubalová, Albena T, Dinkova-Kostova, David, Biedermann, Vladimír, Křen, Jitka, Ulrichová, Jiří, Vrba |
| المصدر: | Fitoterapia |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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 |
| تدمد: | 1873-6971 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=pmid________::99487d2bc78654f7342479f183a8f101Test https://pubmed.ncbi.nlm.nih.gov/28450126Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.pmid..........99487d2bc78654f7342479f183a8f101 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18736971 |
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