Warfarin is a commonly used anticoagulant drug and is a derivate of coumarin. Cytochrome P450 2C9 (CYP2C9) plays the key role in transformation of coumarin and thus, influences determination of warfarin dosage. A number of factors including dietary compounds such as sesamin, caffeic acid and ferulic acids can regulate the activity of CYP2C9. The present study tested the hypothesis that sesamin, episesamin, caffeic acid and ferulic acid decreases the rate of warfarin 7-hydroxylation via inhibition of hepatic CYP2C9. The experiments were conducted on hepatic microsomes from human donors. It was demonstrated that the rate of 7-hydroxylation of warfarin was significantly decreased in the presence of sesamin in the range of concentrations from 5 to 500 nM, and was not affected by episesamin, caffeic acid and ferulic acid in the same range of concentrations. The kinetic analysis indicated non-competitive type of inhibition by sesamin with Ki = 202 ± 18 nM. In conclusion, the results of our in vitro study revealed that sesamin was able to inhibit formation of a major metabolite of warfarin, 7-hydroxywarfarin. The potentially negative consequences of the consumption of high amounts of sesamin-containing food or dietary supplements in warfarin-treated patients need to be further studied.
- MeSH
- antikoagulancia metabolismus MeSH
- dioxoly chemie farmakologie MeSH
- hydroxylace MeSH
- inhibiční koncentrace 50 MeSH
- jaterní mikrozomy metabolismus MeSH
- kinetika MeSH
- kyseliny kávové farmakologie MeSH
- kyseliny kumarové farmakologie MeSH
- lidé MeSH
- lignany chemie farmakologie MeSH
- potraviny MeSH
- potravní doplňky MeSH
- warfarin metabolismus MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Prolyl oligopeptidase is a cytosolic serine peptidase that hydrolyses proline-containing peptides at the carboxy terminus of proline residues. It has been associated with schizophrenia, bipolar affective disorder, and related neuropsychiatric disorders and therefore may have important clinical implications. Thirty-one isoquinoline alkaloids of various structural types, previously isolated in our laboratory, were screened for their ability to inhibit prolyl oligopeptidase. Promising results have been showed by alkaloids californidine (IC50=55.6±3.5 μM), dihydrosanquinarine (IC50=99.1±7.6 μM), corypalmine (IC50=128.0±10.5 μM) and N-methyllaurotetanine (IC50=135.0±11.7 μM).
- MeSH
- alkaloidy chemie MeSH
- aporfiny chemie MeSH
- dioxoly chemie MeSH
- heterocyklické sloučeniny tetra- a více cyklické chemie MeSH
- inhibitory serinových proteinas chemie MeSH
- isochinoliny chemie MeSH
- molekulární struktura MeSH
- serinové endopeptidasy chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The structure of the quaternary tetrahydroprotoberberine alkaloid escholidine is revised on the basis of 2D NMR spectroscopy and X-ray diffraction. In contrast to the originally reported constitution, escholidine bears an -OH group at C-9 and an -OCH3 group at C-10. The 1H and 13C NMR data and long-range 1H-13C and NOE interactions of escholidine are compared with those of thalifendine and tetrahydroberberrubine. The 15N NMR data of escholidine obtained by using long-range 1H-15N correlation experiments at natural abundance are also reported.
