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Statements

Subject Item
n2:RIV%2F61989592%3A15110%2F02%3A00006948%21RIV09-MSM-15110___
rdf:type
n8:Vysledek skos:Concept
dcterms:description
Silybin a jeho příbuzné flavonolignany jsou hlavními složkami extraktu ze Silybum marianum, silymarinu, který byl po stovky let používán k léčbě jaterních onemocnění. Ačkoliv je považován za bezpečný, mnoho jeho složek nebylo nikdy testováno v souvislosti s biotransformací léčiv. Cytochromy P450 (CYP) jsou v tomto ohledu velmi důležité. Testovali jsme účinky čtyř flavonolignanů: silybinu, jeho semisyntetického derivátu dehydrosilybinu, silydianinu a silychristinu na tři specifické CYP aktivity: bufuralol 1´-hydroxylaci (CYP2D6), p-nitrofenol hydroxylaci (CYP2E1) a oxidaci nifedipinu (CYP3A4). Všechny flavonolignany vykazovaly inhibici těchto aktivit v závislosti na dávce, s hodnotou IC50 v mikromolární oblasti. Inhibice byla kompetitivní nebo smíšená, což ukázaly grafy dvojitě reciproké závislosti. Ovšem tato inhibice není relevantní pro terapii, protože fyziologické koncentrace jednotlivých flavonolignanů nepřesahují 0,5 mikromolární. Data podporují využití extraktu jako potravního doplňku. Silybin and related flavonolignans form a major part of the Silybum marianum extract, silymarin, which has been used to treat liver diseases for hundreds of years. Although regarded as safe, many of the extract constituents remain thus far untested for their possible effects on liver biotransformation enzymes. Cytochromes P450 (CYP) are very important in this regard. We tested the effect of four flavonolignans: silybin, its hemisynthetic derivative dehydrosilybin, silydianin, and silycristin on three specific CYP activities: bufuralol 1'-hydroxylation (CYP2D6), p-nitrophenol hydroxylation (CYP2E1), and nifedipine oxidation (CYP3A4). All flavonolignans displayed dose-dependent inhibition of these activities with IC(50) values in the micromolar range. The inhibition was competitive or mixed as revealed by double reciprocal plots of kinetic experiments. However, the inhibition is not considered to be relevant for therapy because physiological concentrations of the individual flavonolignans do not ex Silybin and related flavonolignans form a major part of the Silybum marianum extract, silymarin, which has been used to treat liver diseases for hundreds of years. Although regarded as safe, many of the extract constituents remain thus far untested for their possible effects on liver biotransformation enzymes. Cytochromes P450 (CYP) are very important in this regard. We tested the effect of four flavonolignans: silybin, its hemisynthetic derivative dehydrosilybin, silydianin, and silycristin on three specific CYP activities: bufuralol 1'-hydroxylation (CYP2D6), p-nitrophenol hydroxylation (CYP2E1), and nifedipine oxidation (CYP3A4). All flavonolignans displayed dose-dependent inhibition of these activities with IC(50) values in the micromolar range. The inhibition was competitive or mixed as revealed by double reciprocal plots of kinetic experiments. However, the inhibition is not considered to be relevant for therapy because physiological concentrations of the individual flavonolignans do not ex
dcterms:title
Effect of silybin and its congeners on human liver microsomal cytochrome P450 activities Effect of silybin and its congeners on human liver microsomal cytochrome P450 activities Účinky silybinu a jeho derivátů na aktivitu cytochromů P450 v mikrosomech lidských hepatocytů
skos:prefLabel
Effect of silybin and its congeners on human liver microsomal cytochrome P450 activities Účinky silybinu a jeho derivátů na aktivitu cytochromů P450 v mikrosomech lidských hepatocytů Effect of silybin and its congeners on human liver microsomal cytochrome P450 activities
skos:notation
RIV/61989592:15110/02:00006948!RIV09-MSM-15110___
n4:aktivita
n12:Z n12:P
n4:aktivity
P(GA303/99/P002), Z(MSM 151100003)
n4:cisloPeriodika
7
n4:dodaniDat
n15:2009
n4:domaciTvurceVysledku
n6:8069239 n6:1030957 n6:2514559 n6:7271859 n6:8738394
n4:druhVysledku
n17:J
n4:duvernostUdaju
n11:S
n4:entitaPredkladatele
n16:predkladatel
n4:idSjednocenehoVysledku
644317
n4:idVysledku
RIV/61989592:15110/02:00006948
n4:jazykVysledku
n18:eng
n4:klicovaSlova
cytochrome P450; Silybum marianum; flavonolignans; microsomes; human
n4:klicoveSlovo
n5:Silybum%20marianum n5:human n5:cytochrome%20P450 n5:microsomes n5:flavonolignans
n4:kodStatuVydavatele
US - Spojené státy americké
n4:kontrolniKodProRIV
[2497A6D4A928]
n4:nazevZdroje
Phytotherapy Research
n4:obor
n10:FR
n4:pocetDomacichTvurcuVysledku
5
n4:pocetTvurcuVysledku
7
n4:projekt
n13:GA303%2F99%2FP002
n4:rokUplatneniVysledku
n15:2002
n4:svazekPeriodika
16
n4:tvurceVysledku
Zuber, Roman Rohovský, Petr Šimánek, Vilím Ulrichová, Jitka Dvořák, Zdeněk Modrianský, Martin Anzenbacher, Pavel
n4:zamer
n14:MSM%20151100003
s:issn
0951-418X
s:numberOfPages
7
n19:organizacniJednotka
15110