• Biomedical Science Letters
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• v.1 no.1
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• pp.89-94
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• 1995

Considering the planar structure and nonpolar properity of benzo(a)pyrene(B(a)p) and the planar heme part of cytochrome P-450, stacking interaction is probable. MO calculation on B(a)P and heme part of cytochrome P-450 were carried out to dertermine probable stacking interaction models. In this case, orbital interaction is most important. Accordingly, the stacking positions have high eigen vector in frontier orbital and boning type between two molecules. In this way, five probate models were selected and examined by MN2 and MO method. The most probable .stacking interaction model which is the 4, 5, 6 positions of B(a)P overlap carbon atom and pyrrole ring of ring of heme group was determined.

• Mass Spectrometry Letters
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• v.4 no.2
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• pp.34-37
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• 2013

Honokiol and magnolol, the major bioactive neolignans of magnolia officinalis, are the most important constituents of the crude drug prescriptions that are used in the therapy of neuroses and various nervous disorders. There have been limited reports on the effects of neolignoid compounds on human cytochrome P450 activity. Therefore, the inhibitory effects of honokiol and magnolol on seven human cytochrome P450 s were evaluated in human liver microsomes. Honokiol and magnolol showed the most potent inhibition of CYP1A2-mediated phenacetin O-deethylase activity ($IC_{50}$ values of 3.5 and 5.4 mM, respectively) among the seven P450s tested. These in vitro data indicate that neolignan compounds can inhibit the activity of CYP1A2 and suggest that these compounds should be examined for potential pharmacokinetic drug interactions in vivo.

• Toxicological Research
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• v.26 no.3
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• pp.171-175
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• 2010

The human genome contains approximately 13 orphan cytochrome P450 (P450, CYP) genes, of which the apparent function or substrate has not been identified. However, they seem to possess their own biological relevance in some tissues or developmental stages. Here, we characterized the heterologously expressed CYP2W1, an orphan P450 enzyme. The recombinant CYP2W1 protein containing a $6{\times}$(His)-tag at Nterminus has been expressed in Escherichia coli and purified. Expression level of CYP2W1 holoenzyme was around 500 nmol P450 holoenzyme per liter culture medium. The reduced CO difference spectrum of CYP2W1 showed a maximum absorption at 449 nm. CYP2W1 indicated the significant induction to bioactivate Trp-P-1, MeIQ, and IQ in E. coli DJ701 tester strain. However, the bioactivation of B[$\alpha$]P, and NNK by CYP2W1 was relatively low. The model structure of CYP2W1 suggested the characteristic P450 folds with the lengths and orientations of the individual secondary elements. The F-G loop is situated on the distal side of heme to accommodate the flexibility of active site of CYP2W1. These studies can provide useful information for the finding of its biological roles and structure-function relationships of an orphan CYP2W1 enzyme.

• Toxicological Research
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• v.11 no.2
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• pp.205-213
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• 1995

This study was undertaken to investigate the effects of organic solvents on xenobiotic metabollzing enzyme system in vivo by meaas of experimental conditions i.e. (1) single group which was treated by benzene (B), toluene (T) and xylene (X), respectively, (2) combination group which was treated by mixture of benzene+toluene (BT), benzene+xylene (BX), and toluene+xylene (TX), respectively, (3) mixture group which was treated by benzene+ toluene+xylene mixture (M), and to interpreat the interaction between the organic solvents metabolizing enzymes. 1. The contents of cytochrome P-450 in liver microsomes were increased (p < 0.01) in organic solvents treated groups, and the contents of cytochrome P-450 were increased by following order of B < T < M < BT=BX < X < TX. 2. The activity of cytochrome P-450 dependent AHHase was significantly higher in organic solvents treated groups than in control group (p < 0.01), and the activity of AHHase was increased by following order of B < T < BT=BX=TX=xylene < M. 3. The activity of NADPH P-450 reductase was significantly higher in organic solvents treated groups than in control group (p < 0.01), and the order of M < combinated group < X < T

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.6
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• pp.759-767
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• 1997

In the present study, we characterized the non-vascular smooth muscle relaxant effects of a novel benzoyran derivative ,SKP-450 (2-[2'(1',3'-dioxolone)-2-methyl-4- (2'-oxo-1'-pyrrolidinyl) -6-nitro-2H-1- benzopyran) and its metabolite, SKP-310, in comparison with levcromakalim (LCRK). In the rat stomach fundus, the spontaneous motility stimulated by $10^{-6.5}\;M$ bethanechol was completely eliminated not only by $10^{-7}\;M$ SKP-450 but also by $10^{-6}\;M$ LCRK, which were blocked by $10^{-6}\;M$ glibenclamide. The inhibitory effect of SKP-450 $pD_2,\;3.94{\pm}0.66)$ was much less than LCRK $(pD2,\;5.73{\pm}0.38,\;p<0.05)$. In the bethanechol $(10{-6.5 }\;M)-stimulated$ urinary bladder, the tonus was decreased in association with elimination of spontaneous motility by $10^{-7}\;M$ M SKP-450 and $10^{-6}\;M\;LCRK\;(pD2,\;6.77{\pm}0.06)\;(P<0.05)$, which were inhibitable by $10^{-6}\;M$ glibenclamide. The inhibitory effect of SKP-450 $(pD2,\;7.66{\pm}0.05)$ was significantly more potent than that of LCRK $(pD2,\;6.77{\pm}0.06,\;p<0.05)$. In the rat uterus stimulated by $PGF_{2\alpha}\;(10^{-7}\;M)$, both increased tonus and spontaneous motility were eliminated by $10^{-6}\;M$ LCRK with slight depression of the tonus, but not by SKP-450 $(10^{-5}\;M)$. The stimulated trachea of guinea-pig by $10^{-6.5}\;M$ bethanechol was moderately suppressed by SKP-450 $(10^{-6}{sim}10^{-5}\;M)$ but little by SKP-310. In association with the relaxant effects, SKP-450 $(10^{-6}\;M)$ and LCRK $(10^{-5}\;M)$ caused a significant stimulation of the $^{86}Rb$ efflux from rat urinary bladder and stomach fundus, which were antagonized by $10^{-5}\;M$ glibenclamide, whereas the $K^+$ channel openers could not exert a stimulation of the $^{86}Rb$ efflux from rat uterus. In conclusion, it is suggested that SKP-450 exerts potent relaxant effects on the urinary bladder detrusor muscle and duodenum, whereas it shows much less effect on stomach fundus and uterus as contrasted to LCRK.

• Journal of Genetic Medicine
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• v.20 no.1
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• pp.25-29
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• 2023

The CYP11A1 gene encodes for the cholesterol side-chain cleavage enzyme (P450scc), which initiates steroid hormone biosynthesis. Defective P450scc activity results in severe glucocorticoid and mineralocorticoid deficiencies. We describe a case of P450scc deficiency due to a novel homozygous CYP11A1 variant inherited from the mother with a possibility of uniparental disomy (UPD). The patient was a female, had no family history of endocrine disease, and showed adrenal insufficiency at 13 days of age. Hormonal analysis with an adrenocorticotropic hormone stimulation test showed both glucocorticoid and mineralocorticoid deficiencies, presumed to be a defect of the early stage of steroidogenesis. Exome sequencing reported a novel homozygous frameshift variant of CYP11A1 (c.284_285del, p.Asn95Serfs*10), which was inherited from the mother. Additionally, homozygosity in 15q22.31q26.2, which included CYP11A1, was identified using a chromosomal microarray. It was suggested that the possibility of maternal UPD was involved as the cause of a P450scc deficiency by unmasking the maternally derived affected allele. To our understanding, P450scc deficiency associated with UPD encompassing CYP11A1 had not been reported in Korea before. Genetic analysis can help diagnose rare causes of primary adrenal insufficiency, including P450scc deficiency.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.6
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• pp.1534-1542
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• 2007

In this study, the liver protective effect of the hot water extracts of Scutellaria radix (SR) was investigated. The SR exhibited a hepatoprotective activity against $CCl_4$-induced liver damage in Sprague-Dawley (SD) rats and Chang cell. And the SR also showed significant decrease of malodialdehyde (MDA) and increase of glutathion (GSH), catalase activity in rat liver homogenate. The expression of cytochrome P450 2E1 (CYP2E1), measured by RT-PCR and western blot, was significantly decreased in the SR treated SD rats and Chang cell. But $CCl_4$ and SR has no significant effect on 1A1 and 3A1 isoform of cytochrome P450. Based on these findings, it is suggested that hepatoprotective effects of SR possibly related to antioxidative effects and downregulation of CYP2E1 expression.

• Journal of Society of Preventive Korean Medicine
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• v.15 no.1
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• pp.1-16
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• 2011

Objectives : The mechanisms for korean traditional medicine-drug interaction has not been well reviewed in spite that the chance for co-administration with western drugs or diet supplements has been increased. Especially, it is well known that various cytochrome P450s play a major role in drug-drug interaction. Of course, Korean traditional medicines is not excluded in a view of metabolism or biotransformation by cytochrome P450. This article was focused on reviewing the possible roles of cytochrome P450 in Korean traditional medicine-drug interaction, Also, the directions for further studies were suggested in terms of Korean traditional medicine-drug interaction. Methods : New studies for korean traditional medicine-drug interaction were reviewed and summarized in terms of cytochrome P450 activities by various Korean traditional medicines and western drugs. Results and Conclusions : Even if a few studies related to Korean traditional medicine-drug interactions was carried out, almost no studies for Korean traditional medicine-drug interactions has been found in a view of cytochrome P450. It was suggested that Korean traditional medicines and their decoction should be analyzed that how they effects on cytochrome P450, expecially CYP 1, 2, 3 families and how they interact with western drugs.

• Preventive Nutrition and Food Science
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• v.8 no.2
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• pp.130-136
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• 2003

The protective effects of onion extract (OE), onion powder extracted in ethanol for 2 days. on carbon tetrachloride ($CCl_4$)-induced hepatotoxicities and the possible mechanisms involved in this protection were investigated in mice. Pretreatment with OE prior to the administration of $CCl_4$ significantly reduced the increase in serum alanine and aspartate aminotransferase activities and hepatic lipid peroxidation in a dose-dependent manner. In addition, pretreatment with OE significantly prevented the depletion of reduced glutathione content in the liver of $CCl_4$-intoxicated mice. $CCl_4$-induced hepatotoxicity was also prevented, as indicated by a liver histopathologic findings. The effects of OE on the cytochrome P450 (P450) 2E1, the major isozyme involved in $CCl_4$ biotransformation were investigated. Treatment of mice with OE resulted in a significant decrease in P450 2E1-dependent p-nitrophenol and aniline hydroxylation in a dose-dependent manner. Consistent with these observations, the P450 2E1 expressions were also decreased, as determined by immunoblot analysis. OE also exhibited antioxidant effects in FeCl$_2$-ascorbate induced lipid peroxidation in rat liver homogenates and in superoxide radical scavenging activity. These results show that the protective effects of OE against the $CCl_4$-induced hepatotoxicity may be due to its ability to block bioactivation of $CCl_4$, mainly tty inhibiting the expression and activities of P450 2E1 and by scavenging free radicals.

• Korean Journal of Biological Psychiatry
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• v.7 no.1
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• pp.14-20
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• 2000

Recently atypical antipsychotics have been used as first line agent in the treatment of schizophrenia, and also played a significant role in the treatment of many kinds of psychiatric disorders. The pharmacokinetic and pharmacodynamic properties of these newer antipsychotics are well known through preclinical and early clinical trials. However, it is important to note the limitations of the results due to its relatively short experience. Clozapine is eliminated principally by the hepatic P450 1A2 and 3A4 cytochrome enzymes. 1A2 inducers such as carbamazepine and smoking can reduce its half-life, while 1A2 inhibitors such as SSRIs, especially fluvoxamine can increase its duration of action. Carbamazepine should be avoided in a patient on clozapine because of carbamazepine's potential effects on bone marrow. Benzodiazepines tend to increase the chances of sedation, delirium and respiratory depression. Risperidone is metabolized to 9-hydroxyriperidone by the hepatic P450 2D6 cytochrome enzymes. Fluoxetine and paroxetine, 2D6 inhibitors interfere with metabolism, but 9-hydroxyrisperidone has similar biological activity as parental drug, so it has little affect on the outcome. Olanzapine shows minimal capacity to inhibit cytochrome P450 isoenzymes and shows minimal chance of drug interaction. It is eliminated principally by the hepatic P450 1A2 and 2D6 cytochrome enzymes.