• YAKHAK HOEJI
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• v.28 no.1
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• pp.29-33
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• 1984

The paper aimed to review the influences of ginseng on the metabolism of foreign substances and on the activity of hepatic drug metabolizing enzyme system in mouse or rat liver. It has been known that ginseng components reduces the motality rates and the toxic effects induced by foreign materials. Chronic pretreatment of mouse or rat with ginseng extract fractions or saponin caused the increase in the metabolism of foreign materials and the activity of drug metabolizing enzymes, such as cytochrome $P_{450}$, NADPH cytochrome C reductase and glucuronyl S-transferase in liver. Thus, it may be concluded that decrease in toxic effect of foreign substances by ginseng pretreatment may be partly related to the induction of drug metabolizing enzymes in liver.

• YAKHAK HOEJI
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• v.28 no.1
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• pp.53-59
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• 1984

Drug-metabolizing system which has the important role in drug metabolism is localized in smooth endoplasmic reticulum of hepatocytes and is composed of NADPH, NADPH-cytochrome $P_{450}$ reductase, cytochrome $P_{450}$ and others. It is well known that the enzyme system is induced by phenobarbital and methylcholanthrene. Lipid peroxidation is reaction of oxidative deterioration of polyunsaturated lipids. Formation of lipid peroxides in liver microsome has been found to produce degradation of phospholipid, which are major components of microsomal membrane. The relationship between the formation of lipid oxides and the activities of drug-metabolizing enzyme in the liver of rats was reported by several investigators. In this study the effect of riboflavin tetrabutylate, an antioxidant on lipid peroxidation, specially the relationship between lipid peroxidation and drug-metabolizing enzyme system was investigated. In addition the effect of vitamin A derivatives, such as retinoic acid and retinoid on the enzyme was also observed. Results are summarized as followings. 1) The pretretment with riboflavin tetrabutylate inhibited completely the lengthened sleeping time due to $CCl_{4}$ treatment. 2) The increase of TBA value was prevented by the pretreatment with riboflavin tetrabutylate. 3) The pretreatment with riboflavin tetrabutylate also prevented the decrease of drug-metabolizing enzyme caused by $CCl_{4}$. 4) Both retinoic acid and retinoid remarkably decreased the activity of aminopyrine demethylase. Pretreatment of riboflavin tetrabutylate, however, prevented inhibitory effect of retinoic acid on the enzyme activity.

• Korean Journal of Pharmacognosy
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• v.34 no.1 s.132
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• pp.86-90
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• 2003

For the determination of inhibiting cytochrome P450(CYP)3A4 activity, an improvement HPLC method was established by using a new internal standard and solvent system. Moreover, CYP3A4 amount for a optimum reaction of enzyme was determined by a comparative study with a variety concentration of enzyme. Using a established method, inhibitory effect of CYP3A4 that is drug metabolizing enzyme Investigated on EtOAc extracts of 5-class spices. As a result of experiment, EtOAc extract of white pepper (Piper nigrum L.) showed strong inhibitory activity. On a continuous experiment, the fraction 2, 4 and 5 of while pepper extract showed remarkable inhibitory activity. Pipeline, a main constituent of pepper was not included in these fraction. It is suggested that major compounds for the inhibitory activity of white pepper may be other ingredient that is not piperine.

• Korean Journal of Pharmacognosy
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• v.19 no.1
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• pp.19-27
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• 1988

The hexane and ether extracts from the roots of Angelica dahurica caused a significant inhibition of hepatic drug-metabolizing enzyme (DME) activity. Through systematic fractionation by $SiO_2\;column$ and vacuum liquid chromatography monitoring by bioassays, three furanocoumarins, phellopterin, byakangelicin and tert-O-methylbyakangelicin were isolated as active principles. These components have biphasic responses, both inhibitory and inducing effects on DME system. Tert-O-methyl byakangelicin was found to have the strongest enzyme inhibitory potency.

• 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.

• Korean Journal of Food Science and Technology
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• v.31 no.2
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• pp.535-539
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• 1999

Soybean has drawn much attention mainly due to its chemopreventive action as well as antiestrogenic effect. Although suppression of breast and prostate cancers were believed to be exerted via antiestrogenic or antiandrogenic activity of genistein, its mechanism of prevention against other cancers has not been clearly demonstrated. We proposed that prevention by soybean from other cancers than sex hormone -related cancers was achieved via modulation of drug-metabolizing enzymes. Addition of acid hydrolysate of 80% methanol extract of soyflour to diet caused a significant induction of quinone reductase, an anticarcinogenic marker enzyme and one of drug-metabolizing enzymes, in mouse lung while it suppressed arylhydrocarbon hydroxylase, involved in bioactivation of procarcinogens, in kidney and small intestine. It is likely that active components exist in a conjugated form and released by acid hydrolysis to be able to affect drug-metabolizing enzyme and exert chemopreventive activity. Benzo(a)pyrene-induced tumor development in mouse lung was greatly reduced by soybean extract supplementation, which is consistent with the extract's capability to modulate favorably arylhydrocarbon hydroxylase and quinone reductase towards chemoprevention.

• 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.

• The Korean Journal of Pharmacology
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• v.16 no.2 s.27
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• pp.45-53
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• 1980

Lipid peroxidation in vitro has been identified as a basic deteriorative reaction in cellular mechanism of aging processes, such as air pollution oxidant damage to cell and to the lung, chlorinated hydrocarbon hepatotoxicity. Many experimental evidences were reported by several investigators that lipid peroxidation could be one of the principle causes for the hepatotoxicity produced by $CCl_4$. It is now reasonably established that $CCl_4$ is activated to a free radical in vivo, that lipid peroxidation occurs very quickly in microsomes prepared from damaged livers, that the peroxidation is associated with loss of enzyme activity of microsomes, and that various antioxidants can protect animals against the hepatotoxic effect of $CCl_4$. Recent studies have drawn attention to some other feature of microsomal lipid peroxidation. Incubation of liver microsomes in the presence of NADPH has led to a loss of cytochrome $P_{450}$. However, the presence of an antioxidant prevented lipid peroxidation and preserved cytochrome $P_{450}$. Decrease of cytochrome $P_{450}$ in microsomes under in vitro incubation can be enhanced by $CCl_4 and these changes were parallel to a loss of microsomal polyunsaturated fatty acid and formation of malonaldehyde. The primary purpose of this experiment was to study the effect of riboflavin tetrabutylate on lipid peroxidation, specially, the relationship between lipid peroxidation and drug metabolizing enzyme system which is located in smooth endoplasmic recticulum as well as the effect of ritoflavin tetrabutylate on drug metabolizing enzyme system of animal treated with $CCl_4$. Albino rats were used for experimental animal. In order to induce drug metabolizing enzyme system, phenobarbital was injected intraperitoneally. $CCl_$ and riboflavin tetrabutylate were given intraperitoneally as solution in olive oil. Microsomal fraction was isolated from liver of animals and TBA value as well as the activity of drug metabolizing enzyme were measured in the microsomal fractions. The results are summerized as following. 1) The secobarbital induced sleeping time of $CCl_4$ treated rat was about 2 times longer than that of the control group. However, the pretreatment with riboflavin tetrabutylate inhibited completely the lengthened sleeping time due to $CCl_4$ treatment. Furthermore TBA value was significantly increased in $CCl_4$ treated rat in comparison to control group tut the increase of TBA value was prevented by the pretreatment with riboflavin tetrabutylate. On the other hand, the activity of hepatic drug metabolizing enzyme was decreased in $CCl_4$ group, however, the pretreatment with riboflavin tetrabutylate also prevented the decrease of the enzyme activity caused by $CCl_4$. 2) The effect of riboflavin tetrabutylate on TBA value and the activity of drug metabolizing enzyme in vitro was similar to in vivo results. Incubation of liver microsome from rat in the presence of $CCl_4$, $Fe^{++}$, or ascorbic acid has led to the marked increase of TBA value, however, the addition of riboflavin tetrabutylate in incubation mixture prevented significantly the increase of TBA value, suggesting the inhibition of lipid peroxidation. In accordance with TBA value, the activity of drug metabolizing enzyme was inhibited in the presence of $CCl_4$, $Fe^{++}$, ascorbic acid but the addition of riboflavin tetrabutylate protected the loss of the enzyme activity in microsome under in vitro incubation.

• Toxicological Research
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• v.12 no.2
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• pp.265-270
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• 1996

Effects of a single administration of dichloromethane (DCM) on the hepatic drug metabollzing activity were determined using adult female rats. Rats were treated with DCM (3 mmol/kg, ip) and the disappearance of antipyrine (100 mg/kg, iv) or ethanol (2 g/kg, ip) from blood was measured. The blood concentration and half-life of antipyrine was not influenced by DCM administration. And DCM did not alter the blood concentration of ethanol measured for 240 min after the treatment. The effect of DCM treatment on in vitro cytochrome P-450-dependent enzyme activities was examined as well. No significant difference in either aniline hydroxylase or aminopyrine N-demethylase was observed in hepatic microsomal fractiorts of rats treated with DCM 24 hr prior to sacrifice. The present study indicates that acutely given DCM does not alter the metabolism of xenobiotics in vivo. The failure of DCM to alter the in vitro hepatic microsomal drug metabolizing activity was also noted.

• Natural Product Sciences
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• v.12 no.2
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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.