• 동의생리병리학회지
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• 제21권6호
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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.

• Mass Spectrometry Letters
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• 제5권3호
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• pp.84-88
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• 2014

Licoricidin isolated from Glycyrrhiza uralensis is known to have anticancer, anti-nephritic, anti-Helicobacter pylori, and antibacterial effects. In this study, a cocktail probe assay and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to investigate the modulating effect of licoricidin on cytochrome P450 (CYP) enzymes in human liver microsomes. When licoricidin was incubated at $0-25{\mu}m$ with CYP probes for 60 min at $37^{\circ}C$, it showed potent inhibitory effects on CYP2B6-catalyzed bupropion hydroxylation and CYP2C9-catalyzed diclofenac 4'-hydroxylation with half maximal inhibitory concentration ($IC_{50}$) values of 3.4 and $4.0{\mu}m$, respectively. The inhibition mode of licoricidin was revealed as competitive, dose-dependent, and non-time-dependent, and following the pattern of Lineweaver-Burk plots. The inhibitory effect of licoricidin has been confirmed in human recombinant cDNA-expressed CYP2B6 and 2C9 with $IC_{50}$ values of 4.5 and $0.73{\mu}m$, respectively. In conclusion, this study has shown the potent inhibitory effect of licoricidin on CYP2B6 and CYP2C9 activity could be important for predicting potential herb-drug interactions with substrates that mainly undergo CYP2B- and CYP2C9-mediated metabolism.

• Journal of Microbiology and Biotechnology
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• 제30권8호
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• pp.1207-1213
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• 2020

Aflatoxin B1 (AFB1) is a mycotoxin produced by Aspergillus flavus (A. flavus). AFB1 is reported to have high thermal stability and is not decomposed by heat treatment during food processing. Therefore, in this study, knowing that AFB1 is metabolized by cytochrome P450 (CYP), our aim was to develop a method to detoxify A. flavus-contaminated maize, under normal temperature and pressure, using Escherichia coli expressing human CYP3A4. First, the metabolic activity of AFB1 by recombinant human CYP3A4 was evaluated. As a result, we confirmed that recombinant human CYP3A4 metabolizes 98% of AFB1. Next, we found that aflatoxin Q1, a metabolite of AFB1 was no longer mutagenic. Furthermore, we revealed that about 50% of the AFB1 metabolic activity can be maintained for 3 months when E. coli expressing human CYP3A4 is freeze-dried in the presence of trehalose. Finally, we found that 80% of AFB1 in A. flavus-contaminated maize was metabolized by E. coli expressing human CYP3A4 in the presence of surfactant triton X-405 at a final concentration of 10% (v/v). From these results, we conclude that AFB1 in A. flavus-contaminated maize can be detoxified under normal temperature and pressure by using E. coli expressing human CYP3A4.

• 약학회지
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• 제57권3호
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• pp.194-198
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• 2013

In the present study we evaluated drug-drug interaction potential of ambroxol and cetirizine mediated by inhibition of CYP isoforms including CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4 using pooled human liver microsomes (HLMs). As measured by liquid chromatography-electrospray ionization tandem mass spectrometry, cetirizine and ambroxol inhibited significantly CYP2E1 but the maximal inhibition was approximately 36% at 10 ${\mu}M$ cetirizine and 28% at 3 ${\mu}M$ ambroxol. In addition, CYP2D6 activity was decreased to approximately 83% of control activity in pooled HLM incubated with 3 ${\mu}M$ ambroxol. Activities of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, and CYP3A4 were not significantly inhibited by cetirizine and ambroxol. Considering their maximal plasma concentration in human ($C_{max}$ of cetirizine is approximately 0.67 ${\mu}M$ and $C_{max}$ of ambroxol is 0.044 ${\mu}M$), these two drugs have very low possibility in drug-drug interaction by CYP inhibition in clinical situations.

• 정신신체의학
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• 제19권2호
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• pp.57-65
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• 2011

많은 심혈관질환약물과 향정신성약물 간에 다양한 약물상호작용이 존재하며 이러한 약물들의 대부분이 시트크롬(cytochrome, CYP)450 효소의 기질, 억제제, 유도제로 작용하면서 약물상호작용이 일어나게 된다. 주로 CYP2D6와 CYP3A4를 억제하는 향정신성약물로 인해 같이 투여되는 심혈관질환약물의 효과가 변할 수 있고 부작용까지 나타날 수 있다. 이런 상황을 고려하고 반대의 경우도 포함하여 흔히 처방되는 두 종류의 약물을 병용 투여하는 경우 고려해야 할 부분에 대해서 심혈관질환약물 분류에 따라 논하였다. 대부분의 베타차단제는 CYP2D6의 대사에 의존하므로 이 대사를 억제하는 bupropion, chlorpromazine, haloperidol, SSRIs, quinidine 등을 사용했을 때 베타차단제의 독성이 나타날 수 있다. 앤지오텐신 관련 약물과 이뇨제가 lithium의 농도를 변화시키는 점도 고려하여야 한다. 칼슘통로차단제 및 콜레스테롤강하제를 CYP3A4의 강력한 억제제인 amiodarone, diltiazem, fluvoxamine, nefazodone, verapamil 등과 함께 사용하였을 때 약물 상호작용에 따른 부작용에 유의하여야 한다. 항부정맥제를 복용하는 환자에서 QT 간격 증가를 야기하는 약물이나 관련 CYP450 효소를 억제하는 약물을 동시에 투여하는 것은 삼가거나 적극적인 관찰이 필요하다. Digoxin과 warfarin이 병용 투여되는 향정신성약물로 인해 혈중 농도가 변하는 것도 임상적으로 중요하다.

• Asian-Australasian Journal of Animal Sciences
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• 제21권7호
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• pp.967-971
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• 2008

We compared the fatty acid composition of adipose tissues prepared from Korean native and Yorkshire pigs that have different characteristics in growth and fat deposition. There was no significant difference in the content of most fatty acids between the two breeds, with the exception of arachidonic acid and cis-11,14,17-eicosatrienoic acid. We also investigated the transcriptional levels of genes encoding three different types of oxygenases, including cytochrome P450 (CYP), lipoxygenase and cyclooxygenase, which metabolize arachidonic acid. We found a significant difference in the expression of the CYP genes, CYP2A13, CYP2U1 and CYP3A4, but no differences for the latter two genes between the two breeds. Our results suggest that the difference in arachidonic acid content between the two breeds was caused by differential expression of the CYP genes. Eventually, different levels of EETs and HETEs produced from arachidonic acid by the activity of CYP might contribute partly to the difference of fatness between the two breeds.

• Archives of Pharmacal Research
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• 제27권7호
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• pp.693-712
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• 2004

The rats with protein-calorie malnutrition (PCM, 5％ casein diet for a period of 4-week) were reported to exhibit 60 and 80％ suppression in the hepatic microsomal cytochrome P450 (CYP) 1 A2 and CYP2C11 levels, respectively, and 40-50％ decreases in CYP2E1 and CYP3A 1/2 levels compared to control (23％ casein diet for a period of 4-week) based on Western blot analysis. In addition, Northern blot analysis showed that CYP1 A2, CYP2E1, CYP2C11, and CYP3A1/2 mRNAs decreased in the state of PCM as well. Hence, pharmacokinetic changes of the drugs in rats with PCM [especially the area under the plasma concentration-time curve from time zero to time infinity (AUC) changes of metabolite(s)] reported from literatures were tried to explain in terms of CYP isozyme changes in the rats. Otherwise, the time-averaged nonrenal clearance ($CL_{NR}$) of parent drug was compared. Pharmacokinetic changes of the drugs in other types of malnutritional state, such as kwashiorkor and marasmus, in both human and animal models were also compared. The drugs reviewed are as follows： diuretics, antibiotics, anticancer agents, antiepileptics, antiarrythmics, analgesics, xanthines, antimalarials, and miscellaneous.

• Archives of Pharmacal Research
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• 제18권3호
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• pp.179-182
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• 1995

Previous study showed that $CCl_4$ administration evoked a rapid decrease in cytochrome $P_{450}$ 2E1 protein soon after the exposure due to posttranslational inhibition(Biochem. Biophys. Res. Commun. 179:449-454, 1991). In this report, aniline hydroxylase and the amounts of immunoreactive $P_{450}$ 2E1 were rapidly decreased during day 1 to 2 and recovered during day 3 to 4 after a single dose of $CCl_4$. The activity of pentoxyresorufin-O-dealkylase was also suppressed at day 1 and began to repair from day 2. However, the decrease in immunoreactive $P_{450}$ 2C content was not observed. The decreases in $P_{450}$ 2E1 enzyme activity and immunoreactive protein by acute $CCl_4$ treatment were accompanied by a decline in $P_{450}$ 2E1 mRNA level. The data thus suggested a pretranslational reduction of $P_{450}$ 2E1 during day 1 to 2 after acute $CCl_4$ treatment.

• Journal of Microbiology and Biotechnology
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• 제25권9호
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• pp.1417-1424
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• 2015

In this study, we tried to characterize Streptomyces peucetius CYP157C4 with homology modeling using three cytochrome P450 (CYP) structures (CYP157C1, CYP164A2, and CYP107L1), having discovered that CYP157C4 lacks the ExxR motif that was considered invariant in all CYPs. We used Discovery Studio 3.5 to build our model after first assessing the stereochemical quality and side-chain environment, and a 7-ethoxycoumarin substrate was docked into the final model. The model-substrate complex allowed us to identify functionally important residues and validate the active-site architecture. We found a distance of 4.56 Å between the 7-ethoxycoumarin and the active site of the heme, and cloning and an in vitro assay of the CYP157C4 showed the dealkylation of the substrate. Since the details regarding this group of CYP structures are still unknown, the findings of this study may provide elucidation to assist with future efforts to find a legitimate substrate.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.404.1-404.1
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• 2002

A LC/MS/MS method for the simultaneous determination of the activities of seven major human drug-metabolizing cytochrome P450s (CYP3A4. CYP2D6. CYP2C9. CYP1A2, CYP2C19, CYP2A6. and CYP2C8) was developed. This method used an in vitro cocktail of specific substrates (midazolam. bufuralol. diclofenac, ethoxyresorufin. S-mephenYlOin. coumarin. and paclitaxel) and LC/MS/MS. The assay incubation time is 20 min and the analysis time is 8 min/sample. (omitted)