• Title/Summary/Keyword: CYP2B1

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Enhanced biosynthesis of artemisinin by environmental stresses in Artemisia annua (환경스트레스 처리에 의한 개똥쑥 artemisinin 생합성 증진)

  • Kyung Woon Kim;Cheol Ho Hwang
    • Journal of Plant Biotechnology
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    • v.49 no.4
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    • pp.307-315
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    • 2022
  • Artemisinin is a secondary metabolite of Artemisia annua that shows potent anti-malarial, anti-bacterial, antiviral, and anti-tumor effects. The supply of artemisinin depends on its content in Artemisia annua, in which various environmental factors can affect the plant's biosynthetic yield. In this study, the effects of different light-emitting diode (LED)-irradiation conditions were tested to optimize the germination and growth of Artemisia annua for the enhanced production of artemisinin. Specifically, the ratio between the red and blue lights in the irradiating LED was varied for investigation as follows: [Red : Blue] = [6 : 4], [7 : 3], and [8 : 2]. Furthermore, additional stress factors like UV-B-irradiation (1,395 ㎼/cm2), low temperature (4℃), and dehydration were also explored to induce hormetic expressions of ADS, CYP, and ALDH1, which are essential genes for the biosynthesis of artemisinin. Quantitative polymerase chain reaction (qPCR) was used to analyze the expression levels of the respective genes and their correlation with the specified conditions. [8 : 2] LED-irradiation was the most optimal among the tested conditions for the cultivation of Artemisia annua in terms of both fresh and dry weights post-harvest. For the production of artemisinin, however, [7 : 3] LED-irradiation with dehydration for six hours pre-harvest was the most optimal condition by inducing around twofold enhancement in the biosynthetic yield of artemisinin. As expected, a correlation was observed between the expression levels of the genes and the contents of artemisinin accumulated.

The Anticancer Effects and Drug Metabolic Enzyme Change by Oral Intake of Agrimonia Pilosa Ledeb (선학초(짚신나물) 경구투여시 항암효과 탐색 및 약물 대사효소의 변화)

  • Rhee, Si-Hyung;Jung, Hee;Lee, Ju-Ah;Go, Ho-Yeon;Choi, Yu-Kyung;Park, Jong-Hyung;Kim, Ji-Hye;Ko, Seong-Kyu;Jun, Chan-Yong
    • Journal of Society of Preventive Korean Medicine
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    • v.13 no.2
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    • pp.51-64
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    • 2009
  • Objective : This research was aimed to investigate the anti-tumor effect, safety, mechanism and metabolizing enzyme of Agrimonia pilosa LEDEB(APL) in female C57B/L mouse. Methods : At first, to evaluate the anti-tumor activity of APL, we divided into four groups, normal, control, APL100(100mg/kg), APL150(150mg/kg). LLC obtained American Type Culture Collection was used. LLC had been inoculated to induce tumor. To measure the anti-tumor effect of APL, we calibrate tumor size and weight. To study for mechanism of anti-tumor in APL, we used western blotting and to know metabolizing enzyme in APL we used to real-time PCR. Results : APL100, APL150 inhibited tumor growth after medicine injected. APL did not only induced caspase-dependent apoptosis in LLC-bearing mouse tumor. In APL100, it were decreased 72% in CYP3A11. In APL150, it were decreased 62%, 75% in CYP3A11 and MRP1a respectively. Conclusion : These results suggests that APL has some anti-tumor effects in female C57B/L mouse tumor. APL should be careful use with other drugs related with CYP3A11 or MRP1a.

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Effects of Rhei Rhizoma, Ephedrae Herba and Scutellariae Radix on the Metabolism of 7-Ethoxycoumarin in Isolated Rat Liver (적출관류 간에서 대황, 마황 및 황금이 7-에톡시쿠마린의 대사에 미치는 영향)

  • Choi, Ki-Hwan;Kim, Soon-Sun;Park, Youn-Joo;Chung, Hye-Joo;Ahn, Mee-Ryung;Seo, Soo-Kyung;Sheen, Yhun-Yhong;Kim, Dong-Sup;Chang, Young-Sup
    • YAKHAK HOEJI
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    • v.42 no.4
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    • pp.422-430
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    • 1998
  • In order to study the effects of Rhei rhizoma, Ephedrae herba and Scutellariae radix on hepatic metabolism, we examined the pretreatment effect of those on the metabolism of 7-e thoxycoumarin (EC). Water extracts (1g/kg) of Rhei rhizoma, Ephedrae herba and Scutellariae radix were administered orally to rats for 7 days, respectively. Livers were then isolated and perfused with 100mcM EC for 2 hours. The metabolites of EC, 7-hydroxycoumarin, sulfate conjugate and glucuronide conjugate were measured in the perfusates. The amount of glucuronide conjugates was decreased in Rhei rhizoma pretreated rats (p<0.01), however, 7-hydroxycoumarin was increased in Ephedrae herba pretreated rats (p<0.01). We examined whether the change of enzyme activity is related to the change of cytochrome P4501A1 and P4502B1 mRNA level in the perfused rat liver, which are responsible for EC metabolism. CYP1A1 and CYP2B1 mRNA level was increased, which was was not statistically significant with rhei rhizoma nor ephedrae herba pretreatment. We also assessed the hepatotoxicity of Rhei rhizoma, Ephedrae herba and Scutellariae radix. The activities of ALT and AST were assayed at 24 hours after 7 days administration. Only the ratio of ALT over AST was increased in ephedrae herba pretreated rats (p<0.05). Lipid peroxidation was increased in Rhei rhizoma treatment (p<0.05), while histopathological examination performed after liver perfusion did not show any difference compared with vehicle treatment. These results suggest that Ephedrae herba pretreatment increases the o-deethy-lation of 7-ethoxycoumarin in rats, which may be mediated by CYP1A1 mRNA induction.

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Research about feature selection that use heuristic function (휴리스틱 함수를 이용한 feature selection에 관한 연구)

  • Hong, Seok-Mi;Jung, Kyung-Sook;Chung, Tae-Choong
    • The KIPS Transactions:PartB
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    • v.10B no.3
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    • pp.281-286
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    • 2003
  • A large number of features are collected for problem solving in real life, but to utilize ail the features collected would be difficult. It is not so easy to collect of correct data about all features. In case it takes advantage of all collected data to learn, complicated learning model is created and good performance result can't get. Also exist interrelationships or hierarchical relations among the features. We can reduce feature's number analyzing relation among the features using heuristic knowledge or statistical method. Heuristic technique refers to learning through repetitive trial and errors and experience. Experts can approach to relevant problem domain through opinion collection process by experience. These properties can be utilized to reduce the number of feature used in learning. Experts generate a new feature (highly abstract) using raw data. This paper describes machine learning model that reduce the number of features used in learning using heuristic function and use abstracted feature by neural network's input value. We have applied this model to the win/lose prediction in pro-baseball games. The result shows the model mixing two techniques not only reduces the complexity of the neural network model but also significantly improves the classification accuracy than when neural network and heuristic model are used separately.

Integrative Omics Reveals Metabolic and Transcriptomic Alteration of Nonalcoholic Fatty Liver Disease in Catalase Knockout Mice

  • Na, Jinhyuk;Choi, Soo An;Khan, Adnan;Huh, Joo Young;Piao, Lingjuan;Hwang, Inah;Ha, Hunjoo;Park, Youngja H
    • Biomolecules & Therapeutics
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    • v.27 no.2
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    • pp.134-144
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    • 2019
  • The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased with the incidence of obesity; however, the underlying mechanisms are unknown. In this study, high-resolution metabolomics (HRM) along with transcriptomics were applied on animal models to draw a mechanistic insight of NAFLD. Wild type (WT) and catalase knockout (CKO) mice were fed with normal fat diet (NFD) or high fat diet (HFD) to identify the changes in metabolic and transcriptomic profiles caused by catalase gene deletion in correspondence with HFD. Integrated omics analysis revealed that cholic acid and $3{\beta}$, $7{\alpha}$-dihydroxy-5-cholestenoate along with cyp7b1 gene involved in primary bile acid biosynthesis were strongly affected by HFD. The analysis also showed that CKO significantly changed all-trans-5,6-epoxy-retinoic acid or all-trans-4-hydroxy-retinoic acid and all-trans-4-oxo-retinoic acid along with cyp3a41b gene in retinol metabolism, and ${\alpha}/{\gamma}$-linolenic acid, eicosapentaenoic acid and thromboxane A2 along with ptgs1 and tbxas1 genes in linolenic acid metabolism. Our results suggest that dysregulated primary bile acid biosynthesis may contribute to liver steatohepatitis, while up-regulated retinol metabolism and linolenic acid metabolism may have contributed to oxidative stress and inflammatory phenomena in our NAFLD model created using CKO mice fed with HFD.

Comparison of chlorpyrifos resistance in Culex pipiens pipiens (Diptera: Culicidae) collected from Northern and Southern Tunisia

  • DAABOUB, Jabeur;TABBABI, Ahmed;BEN CHEIKH, Raja;LAAMARI, Ali;FERIANI, Mohamed;BOUBAKER, Chokri;BEN JHA, Ibtissem;BEN CHEIKH, Hassen
    • Entomological Research
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    • v.48 no.5
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    • pp.400-404
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    • 2018
  • In this study, we investigated resistance to the organophosphates chlorpyrifos in Tunisian populations of Culex pipiens pipiens. Three field populations were collected from Northern and central Tunisia between 2003 and 2005 and used for the bioassays tests. Our results registered moderate and high levels of resistance to chlorpyrifos which ranged from 33.8 to 111. The chlorpyrifos resistant populations were highly resistant to propoxur indicated an insensitive acetylcholinesterase 1 (AChE 1). The highest frequency of AChE 1 resistant phenotypes (64%) was recorded in the most resistant population (sample # 1). Bioassays conducted in the presence of synergists showed that not esterases were involved as the resistance mechanism to chlorpyrifos. However, CYP450 was partly involved in the resistance of the most resistant sample (# 1). Starch electrophoresis showed that three esterases were present in studied samples: A2-B2, A4-B4 and B12. Results are discussed in relation to the selection pressure caused by insecticide treatments.

Effect of Maturity at Harvest on the Changes in Quality of Round Baled Rye Silage (수확시 숙기가 호밀 라운드베일 사일리지의 품질변화에 미치는 영향)

  • Kim, J.G.;Chung, E.S.;Seo, S.;Kang, W.S.;Ham, J.S.;Kim, D.A.
    • Journal of The Korean Society of Grassland and Forage Science
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    • v.21 no.1
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    • pp.1-6
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    • 2001
  • This experiment was conducted to evaluated the effect of maturity at harvest on the changes in quality of round baled rye silage at forage experimental field of Grassland and Forage Crops Division, National Livestock Research Institute, RDA, Suwon in 1998. The experimental design was a split-plot design with three replications. The main plots were three different harvest stages : boot, heading and flowering stages, and the subplots were days after ensiling : 1, 2, 3, 5, 10, 30, 45, and 60 days. The wilting period of boot, heading and flowering stages were 1, 0.5 and 0.5 days, respectively. The final pH of rye silage was higher in the order of flowering, boot and heading stages. And pH of flowering stage began to change at early fermentation period, but that of boot and heading stages was delayed 1~2 days. Ammonia-N content of boot stage was highest. and that was increased as fermentation progressed. But Ammonia-N of heading stage was decreased to 30 days. then that was increased after 45 days fermentation. Among fermentation periods, inside temperature of deep place was not affected by external temperature. And that of deep place was increased to 3$0^{\circ}C$ at early fermentation. then decreased as fermentation progressed. However surface temperature was affected by external temperature after 10 days. Acetic acid content was not changed with 5 days by harvest stages, but that of boot stage was increased after 10 days. Butyric acid of boot stage was increased after 5 days. but that of heading stage was increased after 10 days. However lactic acid was increased from 1~2% to 6~8%. Lactic acid bacteria (LAB) of heading and flowering stages were highest at 5 days fermentation, and that of boot stage was highest at 10 days fermentation. The results of this study indicate that fermentation of round baled rye silage occur within 5 days. Therefore, any modification should be applied with an 5 days for high quality of round baled rye silage.

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Characteristics of Acetone Enhancement of Microsomal Cytochrome P45O-dependent B(a)P Hydroxylation in 3-Methylcholanthrene-inducible Rat Liver Microsomes

  • Lee, Dong-Wook;Moon, Ja-Young;Lim, Heung-Bin;Sohn, Hyung-Ok;Lee, Young-Gu;Park, Ki-Hyun
    • Journal of the Korean Society of Tobacco Science
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    • v.20 no.2
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    • pp.178-182
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    • 1998
  • Previously, we showed that acetone enhanced aryl hydrocarbon hydroxylase (AHH) activity in only 3-methylcholanthrene (MC)- or $\beta$-naphtoflavone (BNF)-inducible microsomes of rat liver. In the present study, the possible mechanism underlying acetone action on AHH was investigated in the liver microsomes from MC-pretreated rats. Other n-alkylketones except acetone did not increase AHH activity, which rather decreased significantly with the length of alkyl side chain. Acetone had no effect on the activity of NADPH-cytochrome P450 reductase or inhibited the formation of 3-OH benzo(a)pyrene (B(a)P) in nonenzymatic model ascorbic acid system. However, in cumene hydroperoxide (CuOOH)-supported B(a)P hydroxylation, acetone enhanced its velocity remarkably by 30% at the optimal concentration (30 $\mu$M CuOOH and 1.0% acetone). From these results, we conclude that acetone may facilitate the formation of an activated oxygen species or the insertion of oxygen into B(a)P molecule in CYP1A rich microsomes.

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Salt-sensitive genes and their relation to obesity (소금민감성유전자와 비만)

  • Cheon, Yong-Pil;Lee, Myoungsook
    • Journal of Nutrition and Health
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    • v.50 no.3
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    • pp.217-224
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    • 2017
  • Purpose: Although it is well known thatmortality and morbidity due to cardiovascular diseases are higher in salt-sensitive subjects than in salt-resistant subjects, their underlying mechanisms related to obesity remain unclear. Here, we focused on salt-sensitive gene variants unrelated to monogenic obesity that interacted with sodium intake in humans. Methods: This review was written based on the modified $3^rd$ step of Khans' systematic review. Instead of the literature, subject genes were based on candidate genes screened from our preliminary Genome-Wide Association Study (GWAS). Finally, literature related to five genes strongly associated with salt sensitivity were analyzed to elucidate the mechanism of obesity. Results: Salt sensitivity is a measure of how blood pressure responds to salt intake, and people are either salt-sensitive or salt-resistant. Otherwise, dietary sodium restriction may not be beneficial for everyone since salt sensitivity may be associated with inherited susceptibility. According to our previous GWAS studies, 10 candidate genes and 11 single nucleotide polymorphisms (SNPs) associated with salt sensitivity were suggested, including angiotensin converting enzyme (ACE), ${\alpha}$-adducin1 (ADD1), angiotensinogen (AGT), cytochrome P450 family 11-subfamily ${\beta}$-2 ($CYP11{\beta}$-2), epithelial sodium channel (ENaC), G-protein b3 subunit (GNB3), G protein-coupled receptor kinases type 4 (GRK4 A142V, GRK4 A486V), $11{\beta}$-hydroxysteroid dehydrogenase type-2 (HSD $11{\beta}$-2), neural precursor cell-expressed developmentally down regulated 4 like (NEDD4L),and solute carrier family 12(sodium/chloride transporters)-member 3 (SLC 12A3). We found that polymorphisms of salt-sensitive genes such as ACE, $CYP11{\beta}$-2, GRK4, SLC12A3, and GNB3 may be positively associated with human obesity. Conclusion: Despite gender, ethnic, and age differences in genetics studies, hypertensive obese children and adults who are carriers of specific salt-sensitive genes are recommended to reduce their sodium intake. We believe that our findings can contribute to the prevention of early-onset of chronic diseases in obese children by facilitating personalized diet-management of obesity from childhood to adulthood.

Effect of Naringin on the Bioavailability of Losartan in Rats (흰쥐에서 나린진이 로살탄의 생체이용율에 미치는 영향)

  • Lee, Chong-Ki;Choi, Jun-Shik
    • YAKHAK HOEJI
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    • v.53 no.5
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    • pp.259-264
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    • 2009
  • The present study was to investigate the effect of naringin, a flavonoid, on the pharmacokinetics of losartan in rats. Pharmacokinetic parameters of losartan in rats were determined after an oral administration of losartan (9 mg/kg) in the presence or absence of naringin (0.5, 2.5 and 10 mg/kg). The pharmacokinetic parameters of losartan were significantly altered by the presence of naringin compared with the control group (given losartan alone). Presence of naringin significantly (p<0.05, 2.5 mg/kg; p<0.01, 10 mg/kg) increased the area under the plasma concentration?time curve (AUC) of losartan by 43.7~63.0% and peak plasma concentration ($C_{max}$) of losartan by 31.7~45.5%. Consequently, the absolute bioavailability (AB) of losartan in the presence of naringin was 43.8~62.9%, which was enhanced significantly (p<0.05, p<0.01) compared to that in the oral control group (22.4%). The relative bioavailability (R.B.) of losartan increased by 1.44- to 1.63-fold in the presence of naringin. However, there was no significant change in the peak plasma concentration ($T_{max}$) and terminal half-life ($t_{1/2}$) of losartan in the presence of naringin. In conclusion, the presence of naringin significantly enhanced the oral bioavailability of losartan, implying that presence of naringin might be mainly effective to inhibit the cytochrome P450 (CYP)3A-mediated metabolism, resulting in reducing gastrointestinal and hepatic first-pass metabilism and Pglycoprotein (P-gp)-mediated efflux of losartan in small intestine. Concurrent use of naringin or naringin-containing dietary supplement with losartan should require close monitoring for potential drug interactions.