• Preventive Nutrition and Food Science
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• 제3권1호
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• pp.62-66
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• 1998

The effect of dietary capsaicin (8-methyl-N-vanillyl-6-nonenamide, CAP) on drug-metabolizing enzyme activities was investigated in mice. Male ICR mice were divided into 4 groups and fed diets containing 0, 5, 20, 100 ppm CAP for 4 seeks. Hepatic drug-metabolizing enzyme activities and serum alanine aminotransferase and aspartate transaminease activities were measured. There was no difference in hepatic alanine aminotransferse and aspartate transaminase activities among the groups. Hepatic microsomal cytochrome P450 in CAP fed groups, but p-nitrophenol hydroxylase and the cytosolic acitivity of glutathione S-transferase activities were decreased in the dietary CAP supplemetned groups compared to the control. These results suggest that the dietary CAP at a low dose differentially modulates drug-metabolizing enzyme acitvities without causing hepatic toxicity.

• 약학회지
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• 제28권1호
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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.

• 생약학회지
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• 제34권1호통권132호
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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.

• 생약학회지
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• 제19권1호
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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.

• 한국식품과학회지
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• 제31권2호
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• pp.535-539
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• 1999

콩은 항에스트로젠효과와 항암효과를 가지는 것으로 나타나 최근 많은 관심의 대상이 되고 있다. 콩의 전립선암과 유방암 억제 기작으로 항에스트로젠 효과와 항안드로젠 효과가 보고되었지만 다른 조직에서 발현되는 항암활성 특히 화학적으로 유도되는 발암의 억제기작에 대해서는 아직 분명히 밝혀진 바가 없다. 본 연구에서는 콩이 생식기관이외에도 항암활성을 나타내리라 가정하고 그 기작을 규명하고자 하였다. 콩의 메탄올추추출물의 산가수분해물은 생쥐의 폐에서 항암효소계인 quinone reductase의 활성을 유의적으로 증가시켰으며 신장과 소장에서 1상효소계의 지표효소인 arylhydrocarbon hydroxylase효소활성을 억제하는 것으로 나타났다. 따라서 메탄올 추출물에 배당체로 존재하는 화합물이 산처리에 의하여 유리형으로 전환되면서 화학적 발암을 억제하는 활성을 획득하는 것으로 추정된다. 한편 benzo(a)pyrene으로 위암과 폐암을 유발시켰을 때, 콩추출물 첨가 식이는 폐암 발생을 현저히 낮추는 것으로 확인되었다. 이렇듯 화학적발암에 대한 콩 추출물의 방어효과는 약물대사효소계의 조절과 관련이 있는 것으로 추정된다.

• 대한약리학회지
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• 제16권2호
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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.

• 생약학회지
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• 제50권3호
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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.

• Archives of Pharmacal Research
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• 제13권3호
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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.

• 생약학회지
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• 제17권1호
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• pp.91-99
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• 1986

The single treatment of mice with steam distillate, non-volatile ether extract and methanol extract from mace (Arils of Myristica fragrans) caused a significant prolongation of hexobarbital-induced narcosis and increase in strychnine toxicity as well as a significant decrease in hepatic microsomal drug metabolizing enzyme activities. On 7 consecutive daily administrations, however, the duration of hypnosis was markedly shortened and significant increases in the hepatic enzyme activities were shown. With systematic fractionation by $SiO_2$ column chromatography of non-volatile ether fraction monitoring by animal tests a new lignan (mp $70{\sim}72^{\circ}$, MW 328, $[{\alpha}]^{20}_D+5.28$) was isolated as an active principle and its structure was elucidated as (2R, 3S)-1-(3,4-methylendioxyphenyl)-2,3 dimethyl-4-(4-hydroxy-3-methoxyphenyl) butane.

• 생약학회지
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• 제17권3호
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• pp.189-194
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• 1986

The single acute treatment of mice with the steam distillate, non-volatile ether extract and methanol extract from mace, arils of Myristica fragrans(Myristicaceae) caused a significant prolongation of hexobarbital-induced narcosis, an increase in strychnine toxicity as well as a significant decrease in hepatic microsomal drug metabolizing enzyme activities. On seven daily consecutive administrations, however, the duration of narcosis was markedly shortened and significant increases in the hepatic enzyme activities were shown. From the non-volatile ether fraction, macelignan, a new lignan, mp $70{\sim}72^{\circ}$ was isolated as an active principle.