• Archives of Pharmacal Research
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• v.13 no.3
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• pp.265-268
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• 1990

The effects of lignans, related to macelignan, on hepatic microsomal drug-metabolizing enzyme (DME) activity were evaluated to elucidate the structure-activity relationship in mice and rats. The compounds carrying the methylenedioxyphenyl nucleus were found to be the msot potent among compounds tested; which not only produced a marked inhibition of DME with a single dose but a significant induction with repeated treatments. Lack of the methylenedioxy group caused marked decrease in the activity, implying that a methylenedioxy group is essential and of major importance eliciting DME modifying activity.

• Korean Journal of Pharmacognosy
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• v.50 no.3
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• pp.159-164
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• 2019

Zanthoxylum Peel is widely used as a common spice for a variety of foods. In the orient, it has also been used as traditional agents for treating diseases such as indigestion. Recently, Zanthoxylum Peel has been reported to have anti-cancer activity, anti-microbial activity, and anti-inflammatory activity. Chemical components are known sanshool compounds and xanthoxylin. In this study, we were carried out to investigate the constituents of inhibiting a drug metabolizing enzyme CYP3A4 from Zanthoxylum Peel. CYP3A4 is known as an enzyme involved in drug metabolism as monooxygenase containing the heme. As a result of experiment, we found that bergapten ($IC_{50}=18.21{\mu}M$) and quercetin ($IC_{50}=17.27{\mu}M$) isolated from EtOAc extract of Zanthoxylum Peel showed remarkable CYP3A4-inhibiting activities. Structures of the isolated active compounds were established by chemical and spectroscopic means.

• YAKHAK HOEJI
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• v.25 no.4
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• pp.145-151
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• 1981

The effect of ginseng methanol extract on hepatic drug metabolizing enzyme in rat was investigated. The ginseng methanol extract (100mg/kg) was administered orally to Sprague Dawley rats for 7days and the contents of cytochrome $P_{450}$ and NADPH cytochrome c reductase in liver were measured by the method of Stanton et al. and Mazel respectively. The content of liver cytochrome $P_{450}$ and NADPH cytochrome c reductase in the rats treated with ginseng methanol extract (100mg/kg) were increased by 21.9% and l6.6% respectively and their increases were statistically significant. Single i.p. injection of phenobarbital (100mg/kg) to the rats produced approximately 25% increase in cytochrome $P_{450}$ content in this investigation and further stimulation was produced in the rats pretreated with ginseng methanol extract (100mg/kg). On the other hand, single i.p. injection of 95% $CCl_{4}$ (0.5ml/kg) showed 29% decrease in cytochrome $P_{450}$ content and 10.5% decrease in NADPH cytochrome c reductase activity. The degree of inhibition of cytochrome $P_{450}$ content in the rats pretreated with ginseng methanol extract (100mg/kg) was similar to that observed in the $CCl_{4}$ alone treated group, but NADPH cytochrome c reductase activity was increased by 65% in the rats pretreated with ginseng methanol extract (100mg/kg). These results suggest that ginseng is the hepatic drug metabolizing enzyme inducing agent in the rat and the effect is similar to phenobarbital.

• Toxicological Research
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• v.13 no.3
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• pp.183-186
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• 1997

Acute toxicity of pectenotoxin 2 (PTX2) was examined in mice. Treatment of mice with a toxic dose of PTX2 resulted in clinical signs such as ataxia, cyanosis and an abrupt decrease in body temperature. Histopathological studies revealed that the liver is the major target organ for PTX2. Activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and sorbitol dehydrogenase (SDH) were significantly elevated by PTX2 administration. Glucose-6-phosphatase activities were not changed by the treatment. The PTX2 treatment decreased relative liver weight without changing the body weight. The effect of PTX2 on hepatic drug metabolizing enzyme system was determined. An ip dose of PTX2 (200 $\mu$g/kg) induced a significant decrease in the hepatic microsomal protein content. Cytochrome P-450 content, cytochrome b$_5$ content, NADPH cytochrome c reductase, aminopyrine N-demethylase activities, or hepatic glutathione content were not altered by PTX2 treatment.

• Archives of Pharmacal Research
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• v.11 no.2
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• pp.122-126
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• 1988

The effects of psoralen and angelicin on hepatic microsomal drug-metabolizing enzyme (DME) activities were investigated to elucidate the mode of the interaction of furanocoumarins with DME system. A single administration (30 mg/kg,i. p.) of both coumarins to mice cased a significant prolonagation of hexobarbital-induced hypnosis as well as an increase in strychnine toxicity. The inhibitory potencies of both coumarins as measured by rat hepatic microsomal aminopyrine N-demethylase and hexobarbital hydroxylase activities in vitro were considerably weaker than those of other furanocoumarins which possess a side chain moiety. Both coumarins were found to have significant inducing effects of DME system, with repeated treatments of them. The activities of an angular coumarin were stronger than those of a linear coumarin.

• Archives of Pharmacal Research
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• v.11 no.3
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• pp.240-243
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• 1988

The hexane extract from Nutmeg, the seed of Myristica fragrans significantly inhibited hepatic drug-metabolizing enzyme activity. Through systematic fractionation by $SiO_2$ column and vacuum liquid chromatography monitoring by bioassay, three components, myristicin, (I), licarin-B (II) and dehydrodiisoeugenol (III) were isolated as active principles. Compounds II and III, with a single treatment (200mg/kg, i.p.) showed not only a significant prolongation of hexobarbital-induced sleeping time but also a significant inhibition of aminopyrine N-demethylase and hexobarbital hydroxylase activities in mice. Compounds I and II provoked a sleep episode at a subhypnotic dose of HB, suggesting that they possess CNS-depressant properties.

• Korean Journal of Pharmacognosy
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• v.8 no.3
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• pp.115-119
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• 1977

Black pepper (Piper nigrum L.) among several irritating spices tested was highly effective on the duration of hexobarbital hypnosis in mice. Pretreatment of mice with the methanolic extract of black pepper (60mg/kg i.p.) prolonged markedly the duration of hexobarbital sleeping time. Three consecutive daily administrations of the same dose of black pepper extract, however, shortened (37%) the duration of hexobarbital sleeping time. The ether soluble fraction of black pepper extract caused most potent effects on the duration of hexobarbital hypnosis. From the above results, it was postulated that the lipid soluble components of black pepper might considerably change the drug action and metabolism by altering drug metabolizing enzyme systems.

• Environmental Analysis Health and Toxicology
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• v.23 no.3
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• pp.165-170
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• 2008

간의 약물대사는 흡수된 외인성물질의 배설을 위한 중추적인 역할을 수행하면 이 반응은 일상대사와 이상대사효소로 구성된 약물대사효소계에 의해 매개된다. 약물대사효소의 발현과 활성은 외인성물질의 노출에 의해 유도되거나 억제되며 이 결과는 약물상호작용을 발생시키는 주요한 원인이다. 또한 당뇨, 비만, 영양실조, 음주, 염증반응 등의 병적인 생리상태는 간에서 약물대사효소의 발현과 활성을 조절하는 것으로 보고되고 있다. 이러한 변동은 치료약물 또는 환경오염물질에 대한 인체의 반응성에 영향을 미치며 결과적으로 예측하지 못한 부작용이나 독성을 발생시킬 수 있다. 본 논문에서는 당뇨병에서 약물대사효소의 발현변화를 정리하였다.

• Proceedings of the PSK Conference
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• 2005.04a
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• pp.106-112
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• 2005

• Korean Journal of Veterinary Research
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• v.43 no.4
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• pp.579-585
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• 2003

The studies were carried out on the correlation between microsomal lipid peroxidation level and drug metabolizing enzyme activities in rat liver microsomal suspensions on various ages (2-week-old, 2, 4, 8, and 12-month-old). The lipid peroxidation levels of liver homogenates tended to be elevated in a 4-month-old rat livers, but it was a little decreased in 8 and 12-month-old rat livers. The lipid peroxidation levels of microsomal suspension was not shown any significant differences by ages. Lipid peroxidation levels and microsomal cytochrome P450 and NADPH-cytochrome c reductase activity showed a direct correlation (r=0.72 and r=0.64), respectively. The activities of cytochrome P450-dependent aminopyrine-N-demethylase and benzpyrene hydroxylase in rat liver microsomes were increased by ages up to 8-month-old rats and maintained in 12-month-old rats. The correlation between lipid peroxidation levels and these cytochrome-dependent enzyme activities showed a high direct correlation (r=0.97 and r=0.81), respectively.