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Detalji o radu

Inhibition of cytochrome P450 1A2 by flavonoid aglycones most commonly found in Croatian medicinal plants

AUTOR:

MIRZA BOJIĆ;

KOAUTORI:

ŽELJAN MALEŠ;

MARTIN KONDŽA;

HRVOJE RIMAC;

DARIJA ŠARIĆ-MUSTAPIĆ;

ZNANSTVENA PODRUČJA

PRIRODNE ZNANOSTI

KEMIJA

BIOMEDICINA I ZDRAVSTVO

FARMACIJA

SADRŽAJ
Flavonoids are group of secondary plant metabolites, derivatives of phenylchromone. They differentiate based on the structure of the dihydropyron ring and hydroxylation and subsequent methylation and glycosylation. Humans are exposed to flavonoid through everyday diets ; fruits and vegetables present rich sources of flavonoids. Many of them have beneficial effects on health that include antibacterial, antiviral, hepatoprotective, antithrombotic, anti-inflammatory, etc. When ingested, flavonoids usually undergo hydrolysis of sugar moieties and are absorbed as aglycones. These aglycones are metabolized in liver and one of the major enzymes involved in their biotransformation is cytochrome P450 1A2 (CYP1A2). In this study objective was to determine inhibitory effect of flavonoids on CYP1A2. Study was conducted on 30 flavonoids most commonly found in Croatian medicinal plants. All flavonoids were used in 1 µM concentration. Inhibition was determined using O-deethylation of phenacetine as a marker reaction. Reaction mixture was monitored by reverse phase high performance liquid chromatography coupled with diode array detection. In case of metabolic inhibition assay chrysin was the strongest inhibitor decreasing enzyme activity by 82% (P = 0.004), followed by morine 61% (P = 0.025), and hesperetin 45% (P = 0, 029). However, majority of the observed inhibition in metabolic inhibition assay is consequence of direct inhibition. In direct inhibition, other strong inhibitors were morin, isorhamnetin, pinocembrin and hesperetin. As there was no statistically significant difference between direct and time-dependent inhibition, it can be concluded that majority of inhibition comes from direct inhibition of enzyme e.g. competition with a substrate.
SADRŽAJ (eng)
Flavonoids are group of secondary plant metabolites, derivatives of phenylchromone. They differentiate based on the structure of the dihydropyron ring and hydroxylation and subsequent methylation and glycosylation. Humans are exposed to flavonoid through everyday diets ; fruits and vegetables present rich sources of flavonoids. Many of them have beneficial effects on health that include antibacterial, antiviral, hepatoprotective, antithrombotic, anti-inflammatory, etc. When ingested, flavonoids usually undergo hydrolysis of sugar moieties and are absorbed as aglycones. These aglycones are metabolized in liver and one of the major enzymes involved in their biotransformation is cytochrome P450 1A2 (CYP1A2). In this study objective was to determine inhibitory effect of flavonoids on CYP1A2. Study was conducted on 30 flavonoids most commonly found in Croatian medicinal plants. All flavonoids were used in 1 µM concentration. Inhibition was determined using O-deethylation of phenacetine as a marker reaction. Reaction mixture was monitored by reverse phase high performance liquid chromatography coupled with diode array detection. In case of metabolic inhibition assay chrysin was the strongest inhibitor decreasing enzyme activity by 82% (P = 0.004), followed by morine 61% (P = 0.025), and hesperetin 45% (P = 0, 029). However, majority of the observed inhibition in metabolic inhibition assay is consequence of direct inhibition. In direct inhibition, other strong inhibitors were morin, isorhamnetin, pinocembrin and hesperetin. As there was no statistically significant difference between direct and time-dependent inhibition, it can be concluded that majority of inhibition comes from direct inhibition of enzyme e.g. competition with a substrate.
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