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 48h of exposure, 2,3-dehydrosilydianin at concentrations of 25μM 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.

• Klíčová slova
• Flavonolignans, NQO1, Nrf2, Silybin, Silybum marianum, Silymarin,
• MeSH
• exprese genu účinky léků   MeSH
• faktor 2 související s NF-E2 metabolismus   MeSH
• glutamátcysteinligasa genetika   metabolismus   MeSH
• hemoxygenasa-1 genetika   metabolismus   MeSH
• lidé MeSH
• membránové proteiny genetika   metabolismus   MeSH
• molekulární struktura MeSH
• myši MeSH
• NAD(P)H dehydrogenasa (chinon) genetika   metabolismus   MeSH
• nádorové buněčné linie MeSH
• ostropestřec mariánský chemie   MeSH
• silibinin MeSH
• silymarin farmakologie   MeSH
• upregulace MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• faktor 2 související s NF-E2 MeSH
• GCLM protein, mouse MeSH Prohlížeč
• glutamátcysteinligasa MeSH
• hemoxygenasa-1 MeSH
• Hmox1 protein, mouse MeSH Prohlížeč
• membránové proteiny MeSH
• NAD(P)H dehydrogenasa (chinon) MeSH
• NFE2L2 protein, human MeSH Prohlížeč
• Nqo1 protein, mouse MeSH Prohlížeč
• silibinin MeSH
• silidianin MeSH Prohlížeč
• silychristin MeSH Prohlížeč
• silymarin MeSH

Solar ultraviolet radiation is a major environmental factor that has serious adverse effects on the structure and function of the skin. Although the UVB waveband (295-315 nm) represents only 5-10% of incoming UV light, it is very damaging to the skin. The aim of this study was to investigate the effect of Lonicera caerulea berries on UVB-induced damage to SKH-1 hairless mice. Mice were fed a L. caerulea berry-enriched diet (10%, w/w) for 14 days before a single UVB (1000 mJ cm(-2)) treatment. Effects on health status, antioxidant enzyme activity and expression, and DNA damage were evaluated. The bioavailability of L. caerulea phenolic components was also assessed. We found that feeding with L. caerulea berries prevented a decrease in catalase activity and stimulated NADPH quinone oxidoreductase-1, heme oxygenase-1, and gamma-glutamylcysteine synthetase catalytic and modulatory subunit expression in UVB exposed mice. Administration of the L. caerulea berry-enriched diet led to an increase in UVB-reduced interleukin-17 levels and a decrease in keratinocyte-derived chemokine protein expression that was enhanced after UVB treatment. Further, L. caerulea berries reduced UVB-induced DNA damage evaluated as number of single strand breaks, cyclobutane-pyrimidine dimer formation and H2AX phosphorylation, a marker of double strand breaks. Taken together, we provide evidence that oral administration of L. caerulea berries to mice affords at least partial protection from the adverse effects of a single UVB exposure via modulation of antioxidant enzyme activity/expression and reduction of DNA damage.

• MeSH
• dieta * MeSH
• erytrocyty metabolismus   účinky záření   MeSH
• fenoly analýza   moč   MeSH
• glutamátcysteinligasa metabolismus   MeSH
• hemoxygenasa-1 metabolismus   MeSH
• histony metabolismus   MeSH
• interleukin-17 metabolismus   MeSH
• játra enzymologie   účinky záření   MeSH
• katalasa metabolismus   MeSH
• kůže enzymologie   patologie   účinky záření   MeSH
• Lonicera chemie   metabolismus   MeSH
• myši bezsrsté MeSH
• myši MeSH
• NAD(P)H dehydrogenasa (chinon) metabolismus   MeSH
• ovoce chemie   metabolismus   MeSH
• pilotní projekty MeSH
• poškození DNA účinky záření   MeSH
• ultrafialové záření * MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fenoly MeSH
• glutamátcysteinligasa MeSH
• H2AX protein, mouse MeSH Prohlížeč
• hemoxygenasa-1 MeSH
• histony MeSH
• interleukin-17 MeSH
• katalasa MeSH
• NAD(P)H dehydrogenasa (chinon) MeSH

The mechanism of glutathione (GSH) depletion by isoniazid (INH) was studied in M. smegmatis. INH increased the activity of gamma-glutamyl transferase (GGT) whether added before medium inoculation or to actively growing cells. The activity of GGT in cells grown from the beginning in INH-containing medium increased significantly on growth days 2-6. Three-day old M. smegmatis cells treated with INH exhibited a 30-65% increase in the activity of GGT. The activities of gamma-glutamyl-cysteine synthase (GGCS) and GSH synthase (GS) were lowered by 50 and 56% respectively on the second day of growth when M. smegmatis was grown in a medium supplemented with 1.5 mg INH per L. In 3-day old M. smegmatis, INH significantly inhibited the activities of GSH biosynthetic enzymes. The results demonstrate that the increased activity of GGT and decreased activities of GSH biosynthetic enzymes are responsible for GSH depletion by INH in M. smegmatis.

• MeSH
• časové faktory MeSH
• gama-glutamyltransferasa metabolismus   MeSH
• glutamátcysteinligasa metabolismus   MeSH
• glutathion biosyntéza   metabolismus   MeSH
• glutathionsynthasa metabolismus   MeSH
• isoniazid farmakologie   MeSH
• Mycobacterium účinky léků   enzymologie   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• gama-glutamyltransferasa MeSH
• glutamátcysteinligasa MeSH
• glutathion MeSH
• glutathionsynthasa MeSH
• isoniazid MeSH