• Archives of Pharmacal Research
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• 제11권2호
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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.

• Toxicological Research
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• 제13권3호
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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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• 제11권3호
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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.

• 대한수의학회지
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• 제43권4호
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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.

• Advances in Traditional Medicine
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• 제7권3호
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• pp.311-320
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• 2007

The present study was designed to estimate the protective effect of (-) epigallocatechin gallate (EGCG) on ethanol-induced liver injury in rats. Chronic ethanol administration (6 g/kg/day ${\times}$ 60 days) caused liver damage that was manifested by the elevation of markers of liver dysfunction - aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, bilirubin and ${\gamma}$-glutamyl transferase in plasma and reduction in liver glycogen. The activities of alcohol metabolizing enzymes such as alcohol dehydrogenase and aldehyde dehydrogenase were found to be altered in alcohol-treated group. Ethanol administration resulted in the induction of cytochrome p450 and cytochrome-$b_{5}$ activities and reduction of cytochrome-c reductase and glutathione-S-transferase, a phase II drug metabolizing enzyme. Further, ethanol reduced the viability of isolated hepatocytes (ex vivo) as assessed by trypan blue exclusion test and induced hepatocyte apoptosis as assessed by propidium iodide staining. Treatment of alcoholic rats with EGCG restored the levels of markers of liver injury and mitigated the alterations in alcohol metabolizing and drug metabolizing enzymes and cyt-c-reductase. Increased hepatocyte viability and reduced apoptotic nuclei were observed in alcohol + EGCG-treated rats. These findings suggest that EGCG acts as a hepatoprotective agent against alcoholic liver injury.

• 약학회지
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• 제48권5호
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• pp.266-271
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• 2004

Ginger (Zingiber officinale Roscoe) is widely used as a common condiment for a variety of foods and beverages. In addition to its extensive utilization as a spice, the fresh or the processed rhizome is a useful crude drug in traditional Chinese medicine. It is considered to possess stomachic, carminative, stimulant, diuretic and antiemetic properties. Chemical studies on the pungent principles of ginger have been carried out by a number of investigators, and 6-gingerol and 6-shogaol as a major pungent substance have been isolated. In this study, the constituents inhibiting a drug metabolizing enzyme CYP3A4 from ginger were investigated. CYP3A4 is responsible for drug metabolism as heme-containing monooxygenases. As a result of experiment, 10-gingerol (lC$_{50}$ 5.75$\mu$M) isolated from EtOAc extract of ginger showed remarkable inhibitory activity compared to 6-gingerol ($IC_{50}$/ 14.56 $\mu$M) and zingerone ($IC_{50}$/ 379.63 $\mu$M). This paper describes the isolation, structure elucidation, and CYP3A4 inhibitory activity of these compounds. The structure of the compounds were identified by instrumental analysis such as LC-mass spectrometer and NMR.R.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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• pp.142-142
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• 1998

This study has been undertaken to examine the effect of biphenyl dimethyl dicarboxylate (DDB) on rat liver drug metabolizing enzyme in order to understand the mechanism of DDB on improving hepatic toxicity in rat liver. After DDB was administered into male rats for different periods of time, mRNA level of CYP1A1 and CYP2B1 was measured by polymerase chain reaction (PCR). DDB treatment resulted in increase in CYP2B1 mRNA level whereas there was no change in CYP1A1 mRNA level. This effect of DDB was time dependent reaching maximal level by 2-day treatment. DDB dose response study showed that 50mg/kg DDB induced CYP2B1 mRNA to maximal level and DDB icreased CYP2B1 gene expression with dose-dependent manner. Based on studies of lipid peroxidation, serum ALT and AST levels and histopathologic examination showed DDB protection on CCl4 induced hepatotoxiccity.

• 대한약학회:학술대회논문집
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• 대한약학회 2001년도 Proceedings of International Convention of the Pharmaceutical Society of Korea
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• pp.269.3-269.3
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• 2001

• Natural Product Sciences
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• 제12권2호
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• pp.94-100
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• 2006

The essential oil (EC-oil) obtained from the buds of Eugenia caryophyllata (Myrtaceae) was examined for its free radical-scavenging activity, cytotoxicity, and in vivo toxicity. To find the xenobiotic properties of EC-oil, serum thiobarbituric acid reactive substances (TBARS) level and hepatic drug-metabolizing enzyme activities were measured. It was found that EC-oil displayed xenobiotic properties like bromobenzene. The cytotoxicities of eugenol and of the EC-oil were greatly attenuated by the sulfhydryl-containing N-acetyl-L-cysteine (NAC), suggesting that eugenol was susceptible to nucleophilic sulfhydryl. In addition, eugenol also showed potent free radical-scavenging activity in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Moreover, methyleugenol considerably exhibited less cytotoxicity and less potent free radical-scavenging activity than eugenol, and the cell viability of the methyleugenol was more increased with NAC treatment than the eugenol. These results indicate that the phenolic OH in eugenol may play a crucial role in both cytotoxicity and free radical-scavenging activity. The fashion on oxidative stress and hepatic drug-metabolizing enzyme activities of eugenol resembled those of bromobenznene.

• 한국동물학회지
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• 제27권4호
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• pp.221-230
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• 1984

Wistar계 흰쥐 간의 약 70%를 절제한 후 재생중인 나머지 간의 microsome에서 lipid peroxidation과 약물 대사효소중 특징적인 aminopyrine demethylase의 활성도를 측정하고 NADPH-cytochrome c reductase, glutathione peroxidase의 활성도와 cytochrome P-450의 함량을 측정하였다. Aminopyrine demethylase의 활성도는 재생 제1일에 최저치를 나타냈으며 재생이 진행될수록 정상인 수준으로 증가하였고 lipid peroxidation, NADPH-cytochrome c reductase, cytochrome P-450의 함량 역시 재생초기에 급히 감소하여 재생2일에 가장 낮은 값을 나타내며 점차 정상인 수준으로 증가하여 7일 이후에는 정상치에 도달하였다. Glutathione peroxidase의 활성도는 재생중인 간이나 정상인 개체의 간에서 별다른 차이가 없었다. 이것은 재생중인 간에서 재생초기에 cytochrome P-450의 함량과 NADPH-cytochrome c reductase의 활성도 감소가 lipid peroxidation과 약물 대사효소의 활성도 감소를 일으키며 이러한 현상은 부분 간 절제 후 7일 이후에는 거의 나타나지 않았다.