• Mass Spectrometry Letters
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• v.7 no.4
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• pp.106-110
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• 2016

Ginseng, a traditional herbal drug, has been used in Eastern Asia for more than 2000 years. Various ginsenosides, which are the major bioactive components of ginseng products, have been shown to exert numerous beneficial effects on the human body when co-administered with drugs. However, this may give rise to ginsenoside-drug interactions, which is an important research consideration. In this study, acassette assay was performed the inhibitory effects of 12 ginsenosides on seven cytochrome P450 (CYP) isoforms in human liver microsomes (HLMs) using LC-MS/MS to predict the herb-drug interaction. After incubation of the 12 ginsenosides with seven cocktail CYP probes, the generated specific metabolites were quantified by LC-MS/MS to determine their activities. Ginsenoside Rb1 and F2 showed strong selective inhibitory effect on CYP2C9-catalyzed diclofenac 4'-hydroxylation and CYP2B6-catalyzed bupropion hydroxylation, respectively. Ginsenosides Rd showed weak inhibitory effect on the activities of CYP2B6, 2C9, 2C19, 2D6, 3A4, and compound K, while ginsenoside Rg3 showed weak inhibitory effects on CYP2B6. Other ginsenosides, Rc, Rf, Rg1, Rh1, Rf, and Re did not show significant inhibitory effects on the activities of the seven CYPs in HLM. Owing to the poor absorption of ginsenosides after oral administration in vivo, ginsenosides may not have significant side effects caused by interaction with other drugs.

• YAKHAK HOEJI
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• v.58 no.4
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• pp.255-261
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• 2014

Poly-pharmacy has been on the rise because of aging of population and chronic disease. Most of drug metabolism happens in the liver by CYP isozymes and the metabolism by CYP450 enzymes. The Cytochrome P450 (CYP) is a superfamily of enzymes that catalyzes the oxidations of many endogenous and exogenous compounds. Primary human Hepatocytes (HH) are considered as the gold standard model for In vitro drug interaction studies. However, there are several limitations (cost, limited life span) for using HH cells. HepaRG cells are being used as a possible alternative. HepaRG cells were cultured in William E medium containing the positive control inducers (1A2: 10, 25, 50 ${\mu}M$ omeprazole, 2C9 and 2C19: 10 ${\mu}M$ rifampin, 3A4: 10, 25, 50 ${\mu}M$ rifampin) at $37^{\circ}C$, 5 % $CO_2$ in a humidified atmosphere. This study was to evaluate the induction of CYP isozymes (1A2, 2C9, 2C19 and 3A4) using LC-MS/MS. We evaluated the potential induction ability of Bosentan, as a drug of pulmonary artery hypertension, in HepaRG cells. For reference, dose of the Bosentan is determined to the basis of the $C_{max}$ (835 mg/ml) value. The enzyme activity demonstrated that CYP2C9 and 3A4 were induced up to 20 times by Bosentan. Like as In vivo, the enzyme activity of CYP2C9 and CYP3A4 is significantly induced in a dose-dependent by Bosentan.

• The Journal of Korean Medicine
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• v.38 no.2
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• pp.15-30
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• 2017

Objectives: Hwangryunhaedok-tang (HHT; Huanglianjiedu-tang, Orengedoku-to), a traditional herbal formula, is used for treating inflammation, hypertension, gastritis, liver dysfunction, cerebrovascular diseases, dermatitis and dementia. The objective of this study was to assess the sub-acute toxicity of HHT in Sprague-Dawley (SD) rats, and its effect on the activities of human microsomal cytochrome P450s (CYP450s) and UDP-glucuronosyltransferases (UGTs). Methods: Male and female SD rats were orally administered HHT once daily at doses of 0, 500, 1000 and 2000 mg/kg for 4 weeks. We analyzed mortality, clinical observations, body weight, food consumption, organ weights, urinalysis, hematology, serum biochemistry, and histopathology. The activities of major human CYP450s (CYP1A2, CYP3A4, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP2E1) and UGTs (UGT1A1, UGT1A4, and UGT2B7) were assessed using in vitro fluorescence- and luminescence-based enzyme assays, respectively. Results: No toxicologically significant changes related to the repeated administration of HHT were observed in both male and female SD rats. The no observed adverse effect level (NOAEL) value was more than 2000 mg/kg/day for both sexes. HHT inhibited the activities of human microsomal CYP1A2, CYP2C19, CYP2D6, and CYP2E1, whereas it weakly inhibited the activities of CYP2B6, CYP2C9, CYP3A4, and UGT1A1. In addition, HHT negligibly inhibited the activities of human microsomal UGT1A4 and UGT2B7 with $IC_{50}$ values in excess of $1000{\mu}g/mL$. Conclusions: Our findings indicate that HHT may be safe for repeated administration up to 4 weeks. In addition, these findings provide information on the safety and effectiveness of HHT when co-administered with conventional drugs.

• Korean Journal of Biological Psychiatry
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• v.8 no.2
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• pp.208-219
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• 2001

The pharmacotherapy of schizophrenia exhibits wide inter-individual variabilities in clinical efficacy and adverse effects. Recently, human genetic diversity has been known as one of the essential factors to the variation in human drug response. This suggests that drug therapy should be tailored to the genetic characteristics of the individual. Pharmacogenetics is the field of investigation that attempts to elucidate genetic basis of an individual's responses to pharmacotherapy, considering drug effects divided into two categories as pharmacokinetics and pharmacodynamics. The emerging field of pharmacogenomics, which focuses on genetic determinants of drug response at the level of the entire human genome, is important for development and prescription of safer and more effective individually tailored drugs and will aid in understanding how genetics influence drug response. In schizophrenia, pharmacogenetic studies have shown the role of genetic variants of the cytochrome P450 enzymes such as CYP2D6, CYP2C19, and CYP2A1 in the metabolism of antipsychotic drugs. At the level of drug targets, variants of the dopamine $D_2$, $D_3$ and $D_4$, and 5-$HT_{2A}$ and 5-$HT_{2C}$ receptors have been examined. The pharmacogenetic studies in schizophrenia presently shows controversial findings which may be related to the multiple involvement of genes with relatively small effects and to the lack of standardized phenotypes. For further development in the pharmacogenomics of schizophrenia, there would be required the extensive outcome measures and definitions, and the powerful new tools of genomics, proteomics and so on.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.195-195
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• 2001

The inhibitory potentials of TCAs (imipramine, desipramine, amitriptyline, and nortriptyline) on phenytoin p-hydroxylation and probe metabolic pathways of each CYP isoforms were evaluated from incubation studies of human liver microsomes and cDNA-expressed cytochrome P450s in vitro in order to understand the mechanism of drug interaction between TCAs and phenytoin, a substrate of CYP2C9 and CYP2C19. (omitted)

• Bulletin of the Korean Chemical Society
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• v.32 no.spc8
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• pp.2895-2896
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• 2011

• Microbiology and Biotechnology Letters
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• v.19 no.5
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• pp.450-455
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• 1991

A protease hyperproducer, ampicillin resistant mutant, Serratia sp. SMNT-1 was selected from Serratia marcescens ATCC 21074 by mutagenesis. The protease productivity of this strain was about 11 times as much as that of the parental strain. The enzyme showed maximal activity at pH 9.0 and $40^{\circ}C$ and was stable over the pH range from 6.0 to 10.0 at $4^{\circ}C$, whereas it was unstable at $37^{\circ}C$ in alkaline condition. the enzyme was inactivated by heating at $60^{\circ}C$ for 10 min. The enzyme was inactivated by EDTA and reactivated by $Zn^{2+}, Co^{2+},\; and \; Mn^{2+}$, but the proteoiytic activity of the enzyme was not affected by DFP. From the above results, the protease produced by Serratia sp. SMNT-1 was classified as a metalloprotese.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.192-192
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• 1994

본 논문에서는 cytochrome P450 LA1 유전자의 5'-upsteam 조절부위의 클로닝을 실시하였다. pUC19 vector에 연결시킨 3.4 Kb 크기의 Pstl DNA조각을 Sst1, Nco1 제한 효소로 자른 뒤, Exonuclease III 를 처리하여 약 200bp 씩의 차이를 갖는 여러 크기의 plasmid들을 얻었다. 이 plasmid 의 핵산서열을 알아보기 위해 dideoxy nucletide를 이용한 sequencing방법으로 그 핵산서열의 결정 실험을 시도하였다. 또한, 다환상 방향족 탄화수소 화합물에 반응성을 갖는 C57BL/6N 생쥐와 반응성을 갖지않는 DBA/2N 생쥐에 있어 phase II 대사 효소인UDP-glucuronosyltransferase 효소활성에 대한 3-methylcholanthrene의 영향을 알아보기 위해 C57BL/6N 생쥐와 DBA/2N 생쥐에 각각 다른 농도의 3-methylcholanthrene을 처리하거나 각기 다른 시간에 3-methylcholanthrene를 처리하였다. 그 결과 UDP-glucuronosyl-transferase의 mRNA가 3-methylcholanthrene양의 증가에 따라, 처치시간이 길어짐에 따라 증가되어지며 그 mRNA위 크기는 약 2.2Kb 정도임을 알았다. 이로부터 UDP-ghucuronosyltransferase 또한 cytochrome P45O와 함께 다환상 방향족 탄화수소 화합물 조절인자를 통한 조절을 받을 것이며 phase I phase II 약물 대사 효소가 조절상 밀접한 관련을 가짐을 예측할 수 있었다.

• Journal of the Korean Institute of Electrical and Electronic Material Engineers
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• v.19 no.5
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• pp.450-456
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• 2006

In this paper, we report the changes of morphology, transmittance and photoluminescence (PL) in hydrogenated amorphous $As_{40}Ge_{10}Se_{15}S_{35}$ thin films, thermally deposited at the vapor incidence angles (${\theta}$) of $0^{\circ},\;45^{\circ}\;and\;80^{\circ}$. The hydrogenation was carried out under the condition of a $H_2$ pressure ($P_H$) of 20 atm and an annealing temperature range, $T_{Anneal}$ of $150^{\circ}C{\sim}210^{\circ}C$. A columnar structures with an inclination angle of approximately $65{\sim}70^{\circ}$ was formed in $80^{\circ}$-deposited films and then the columnar was broken after hydrogenation. Transmittance increases with an increase of deposition angle and by the hydrogenation. In particular, a broad PL band on the extended region is observed in obliquely deposited films and it increases during the hydrogenation.

• Herbal Formula Science
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• v.30 no.1
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• pp.1-9
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• 2022

Objectives : This study investigated the protective effect of Ojeok-san (OJS) on cellular damage induced by oxidative stress and whether it induces changes in CYP450 expression. Methods : To investigate the protective effect, we used cells stimulated by oxidative stress caused by the combination treatment of AA+iron. Changes in CYP450 expression were detected by immunoblotting analysis using Huh7 cells. Results : We observed that OJS altered the expression of CYP1A2, CYP3A4, CYP2C19, CYP2D6, and CYP2E1. OJS increased cell viability against AA+iron-induced oxidative stress and inhibited mitochondrial dysfunction. OJS increased phosphorylation of LKB1, phosphorylation of AMPK, and phosphorylation of ACC, which are related to the LKB1-AMPK pathway. In addition, phosphorylation of LATS1 and phosphorylation of YAP, which are related to the Hippo-YAP pathway, were increased. Conclusions : Our results show that OJS has 1) the ability to protect hepatocytes against oxidative stress, and 2) the potential to induce changes in CYP450.