• Title/Summary/Keyword: CYP1A2

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Antiestrogenic Effects of Marijuana Smoke Condensate and Cannabinoid Compounds

  • Lee Soo Yeun;Oh Seung Min;Lee Sang Ki;Chung Kyu Hyuck
    • Archives of Pharmacal Research
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    • v.28 no.12
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    • pp.1365-1375
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    • 2005
  • The antiestrogenic effects of marijuana smoke condensate (MSC) and three major cannabinoids, i.e., $\bigtriangleup^{9}$-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN), were evaluated using in vitro bioassays, viz., the human breast cancer cell proliferation assay, the recombinant human estrogen receptor (ER) competitive binding assay, and the reporter gene assay. The inhibitory effects on estrogen were also examined using the ethoxyresorufin-O­deethylase (EROD) assay, the aromatase assay, and the 17$\beta$-estradiol ($E_{2}$) metabolism assay. The results showed that MSC induced the antiestrogenic effect via the ER-mediated pathway, while THC, CBD, and CBN did not have any antiestrogenic activity. This suggests that the combined effects of the marijuana smoke components are responsible for the antiestrogenicity of marijuana use. In addition, MSC induced the CYP1A activity and the $E_{2}$ metabolism, but inhibited the aromatase activity, suggesting that the antiestrogenic activity of MSC is also related to the indirect ER-dependent pathway, as a result of the depletion of the in situ $E_{2}$ level available to bind to the ER. In conclusion, pyrogenic products including polycyclic aromatic hydrocarbons (PAHs) in the non-polar fraction, which is the most biologically active fraction among the seven fractions of MSC, might be responsible for the antiestrogenic effect.

Hepatoprotcetive Effects of Oyster (Crassostrea gigas) Extract in a Rat Model of Alcohol-Induced Oxidative Stress (알코올로 유도된 간 손상 동물모델에서 굴 추출물의 간 보호 효과)

  • Osaki, Kenji;Arakawa, Teruaki;Kim, Bumsik;Lee, Minjae;Jeong, Changsik;Kang, Namgil
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.6
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    • pp.805-811
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    • 2016
  • This study was conducted to investigate the protective effects of water extract from Crassostrea gigas (CGW) against ethanol-induced hepatic toxicity in rats. Seventy-two male Wistar rats (6-week-old) were divided into six groups of 12 animals each: control group (1 mL saline/d), ethanol-treated group, positive control group (ethanol+Hovenia dulcis Thunb extract), CGWL group (ethanol+low dosage of CGW), CGWM group (ethanol+medium dosage of CGW), and CGWH group (ethanol+high dosage of CGW). All groups except the control group received ethanol (40% ethanol 5 g/kg) orally. CGW administration with ethanol resulted in prevention of ethanol-induced hepatotoxicity by increasing levels of serum alanine aminotransferase and ${\gamma}-glutamyltransferase$. CGW supplementation significantly reduced formation of malonaldehyde and inhibited reduction of hepatic glutathione and peroxidase levels, as compared with the ethanol-administration group. Further, CGW suppressed expression of CYP2E1, which was elevated by ethanol administration. Consequently, our results indicate that Crassostrea gigas may exert hepatoprotective effects against alcohol-induced hepatocyte injury by intensifying the anti-oxidative defense system.

Anti-Diabetic Effects of Dung Beetle Glycosaminoglycan on db Mice and Gene Expression Profiling

  • Ahn, Mi Young;Kim, Ban Ji;Yoon, Hyung Joo;Hwang, Jae Sam;Park, Kun-Koo
    • Toxicological Research
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    • v.34 no.2
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    • pp.151-162
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    • 2018
  • Anti-diabetes activity of Catharsius molossus (Ca, a type of dung beetle) glycosaminoglycan (G) was evaluated to reduce glucose, creatinine kinase, triglyceride and free fatty acid levels in db mice. Diabetic mice in six groups were administrated intraperitoneally: Db heterozygous (Normal), Db homozygous (CON), Heuchys sanguinea glycosaminoglycan (HEG, 5 mg/kg), dung beetle glycosaminoglycan (CaG, 5 mg/kg), bumblebee (Bombus ignitus) queen glycosaminoglycan (IQG, 5 mg/kg) and metformin (10 mg/kg), for 1 month. Biochemical analyses in the serum were evaluated to determine their anti-diabetic and anti-inflammatory actions in db mice after 1 month treatment with HEG, CaG or IQG treatments. Blood glucose level was decreased by treatment with CaG. CaG produced significant anti-diabetic actions by inhiting creatinine kinase and alkaline phosphatase levels. As diabetic parameters, serum glucose level, total cholesterol and triglyceride were significantly decreased in CaG5-treated group compared to the controls. Dung beetle glycosaminoglycan, compared to the control, could be a potential therapeutic agent with anti-diabetic activity in diabetic mice. CaG5-treated group, compared to the control, showed the up-regulation of 48 genes including mitochondrial yen coded tRNA lysine (mt-TK), cytochrome P450, family 8/2, subfamily b, polypeptide 1 (Cyp8b1), and down-regulation of 79 genes including S100 calcium binding protein A9 (S100a9) and immunoglobulin kappa chain complex (Igk), and 3-hydroxy-3-methylglutaryl-CoenzymeAsynthase1 (Hmgcs1). Moreover, mitochondrial thymidine kinase (mt-TK), was up-regulated, and calgranulin A (S100a9) were down-regulated by CaG5 treatment, indicating a potential therapeutic use for anti-diabetic agent.

Discovery of a Novel 2,6-Difunctionalized 2H-Benzopyran Inhibitors Toward Sphingosylphosphorylcholine Synthetic Pathway as New Anti-inflammatory Target

  • Lee, Gee-Hyung;Lee, Seong Jin;Jeong, Dae Young;Kim, Ha-Young;Lee, Doohyun;Lee, Taeho;Hwang, Jong-Yeon;Park, Woo Kyu;Kong, Jae-Yang;Cho, Heeyeong;Gong, Young-Dae
    • Bulletin of the Korean Chemical Society
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    • v.35 no.8
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    • pp.2385-2390
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    • 2014
  • Novel 2,6-difuctionalized 2H-benzopyrans were synthesized and evaluated for a sphingosylphosphorylcholine(SPC) inhibitor. The synthetic 2H-benzopyrans 1c and 3a showed high potency in SPC-induced cell proliferation assay ($IC_{50}$ < 20 nM). Neither hERG $K^+$ channel binding (> $10{\mu}M$) nor CYP inhibitions (> $10{\mu}M$) were observed. Also, the simple structure-activity relationship (SAR) results were obtained from analysis of 2H-benzopyran derivatives 1-3 and the anti-SPC effect of 2H-benzopyran 1c was confirmed by a HUVEC tube formation assay.

Immunological Effect of the Cytochrome P450 to Alcohol and Stress in Guinea Pig (알콜과 스트레스가 Cytochrome P450 발현에 미치는 영향에 관한 면역학적 연구)

  • Yang-Hyun Chun;Jung-Pyo Hong
    • Journal of Oral Medicine and Pain
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    • v.20 no.2
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    • pp.461-475
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    • 1995
  • The purpose of this study was to investigate the effect of alcohol and stress on liver and buccal mucosa in guinea pig by immunological methods. Especially, Cytochrome P450 (CYP) which in oxidase during alcohol metabolism and bioactivator to carcinogen was used as an indicator in this study. 48 guinea pigs were used in this study. The experimental guinea pig were divided into three groups: The first was a group with giving alcohol-15%(v/v) ethyl alcohol, the second group was a with giving stress in the $0^{\circ}C$ water and the third was a control group. Every 4 guinea pigs of each group were sacrificed weekly-first, second, third, fourth week after experiment and extracted liver tissues and buccal mucosa. The liver tissues were observed by using immunoblotting technique (Western blot) and buccal mucosa were observed by immunofluorescence technique. The results were as follows: 1. By the alcohol and stress, Cytochrome P450 was amplified positive in the liver tissues at third week. 2. By the alcohol and stress, Cytochrome P450 was not detected in the buccal mucosa at any period.

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Substrate reduction therapy as a new treatment option for patients with Gaucher disease type 1: A review of literatures

  • Sohn, Young Bae;Yoo, Han-Wook
    • Journal of Genetic Medicine
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    • v.13 no.2
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    • pp.59-64
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    • 2016
  • Gaucher disease type 1 (GD1) is an inherited lysosomal storage disorder caused by deficiency of acid ${\beta}$-glucosidase. The diminished enzyme activity leads to the accumulation of substrates and results in multi-systemic manifestations including hepatosplenomegaly, anemia, thrombocytopenia, and bone diseases. Enzyme replacement therapy (ERT) by infusion of recombinant protein has been the standard treatment for over 20 years. Despite the successful long-term treatment with ERT, several unmet needs remain in the treatment of GD1 such as severe pulmonary and skeletal manifestations. Substrate reduction therapy (SRT) reduces the accumulation of substrates by inhibiting their biosynthesis. Eliglustat, a new oral SRT, was approved in United States and Europe as a first-line therapy for treating adult patients with GD1 who have compatible CYP2D6 metabolism phenotypes. Although eliglustat is not yet available in Korea, introduction and summary of this new treatment modality are provided in this paper by review of literatures. Despite the fact that there are only limited studies to draw resolute conclusions, the current data demonstrated that eliglustat is not inferior to ERT in terms of its clinical efficacy. The approval of eligustat enables eligible adult GD1 patients to have the option of oral therapy although it still needs further studies on long-term outcomes. The individual patient should be assessed carefully for the choice of treatment modality when eliglustat becomes available in Korea. Furthermore, the clinical guidelines for Korean patients with GD1 regarding the use of eliglustat needs to be developed in near future.

DEVELOPMENT OF THREE DIMENSIONAL MEASURING PROGRAM WITH FRONTAL AND LATERAL CEPHALOMETRIC RADIOGRAPHS -PART 1. COMPUTATION OF THE THREE-DIMENSIONAL COORDINATES BY COMPENSATION OF THE ERROR OF THE HEAD POSITION IN ORDINARY NON-BIPLANAR CEPHALOSTAT- (정모 및 측모 두부 방사선 규격사진을 이용한 3차원 계측 프로그램의 개발 -1. 단일 방사선원으로 촬영된 두부 방사선사진의 두부 위치 보정을 이용한 3차원 좌표의 산출-)

  • Lee, Geun-Ho;Lee, Sang-Han;Jang, Hyon-Joong;Kwon, Tae-Geon
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.27 no.3
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    • pp.214-220
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    • 2001
  • The clinical application of the three-dimensional radiographic technique had been limited to standard Broadbent-Bolton cephalometer with biplanar stereoradiography. We developed a new method for compensating the error of head position in ordinary non-biplanar cephalostat. It became to possible to use the three dimensional cephalogram commonly in clinical bases. 1. The method of methemetical compensation of head positioning error in non-biplanar condition was evaluated with dry skull. The error of the method of first and the second trial was $0.46{\pm}1.21$, $0.33{\pm}0.90mm$, which means the error of the head positioning correction in conventional cephalogram was within clinical acceptance. 2. The reproducibility of this system for clinical application was 0.54 mm ($-2.99{\sim}2.26mm$) which defines the absolute mean difference of the first and second trial. Compare to the The landmark identification error $1.2{\pm}1.6mm$, the error of the measurement was within the range of landmark identification error. The result indicates the adequate clinical accuracy of the computation of three-dimensional coordinates by compensation of the error of the head position in ordinary non-biplanar cephalostat.

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TREATMENT OF MALOCCLUSION, AS RELATED TO FINGER SUCKING : CASE REPORT (손가락 빨기로 인한 부정교합의 치험례)

  • Moon, Sang-Jin;Choi, Yeong-Chul
    • Journal of the korean academy of Pediatric Dentistry
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    • v.31 no.1
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    • pp.1-10
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    • 2004
  • The habit of finger sucking is a reflex occurring in the oral stage, due to nutritive and psychological desire. The habit of finger sucking is considered to be normal till 3 years of age. Dento-skeletal effect on maxillo-mandibular complex including occlusion is naturally correction, when habit stopped before 3 years. If finger sucking continues till $3{\sim}4$ years, Finger sucking leads to severe malocclusion and remarkable discrepancy maxillo-mandibular complex, which is difficult in expectation of natural correction. It is necessary to positive treatment. Treatment of malocclusion, as related to finger sucking is classified two methods. (psychological approach and orthodontic appliance) To stop a habit and to correct severe skeletal discrepancy and malocclusion, $fr\ddot{a}nkel$ appliance is very effective device. This study is to report two cases of treatment of malocclusion, as related to finger sucking. 2 years 10 months old girl with severe overjet, maxillo-mandibular skeletal discrepancy and severe convex facial profile was treated with a FR-II appliance. Finger sucking habit stopped immediately After 16 months, severe overjet, maxillo-mandibular skeletal discrepancy and severe convex facial profile was corrected. 4 years 2 months old girl with midline deviation, mandibular right shift, collateral posterior crossbite and facial asymmetry was treated with a FR-III appliance. Finger sucking habit stopped immediately. After 10 month, Midline deviation, mandibular right shift, collateral posterior crossbite and facial asymmetry were corrected. FR-appliance is a recommendable appliance for a habit breaker and correction of skeletal discrepancy.

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Association Analysis of the Essential Hypertension Susceptibility Genes in Adolescents: Kangwha Study (청소년 고혈압 관련 유전자의 연관성 분석: Kangwha Study)

  • Suh, Il;Nam, Chung-Mo;Kim, Sung-Joo;Shin, Dong-Jik;Hur, Nam-Wook;Kang, Dae-Ryong
    • Journal of Preventive Medicine and Public Health
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    • v.39 no.2
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    • pp.177-183
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    • 2006
  • Objectives : In this study we examined the association between the genetic markers ACE (A-240T, C-93T, I/D, A2350G), AGT (M235T), AT1R (A1166C), CYP11B2 (T344C, V386A), REN (G2646A), ADRB2 (G46A, C79G, T47C, T1641), GNB3 (C825T) and ADD1 (G460W) and the presence of essential hypertension in adolescents. Methods : The Kangwha Study is an 18-year prospective study that is aimed at elucidating the determinants of the blood pressure level from childhood to early adulthood. For this study, we constructed a case-control dataset of size of 277 and 40 family trios data from the Kangwha Study. For this purpose, we perform a single locus-based case-control association study and a single locus-based TDT (transmission/disequilibrium test) study. Results : In the case-control study, the single locus-based association study indicated that the ADD1 (G460W) (p=0.0403), AGT (M235T) (p=0.0002), and REN (G2646A) (p=0.0101) markers were significantly associated with the risk of hypertension. These results were not confirmed on the TDT study. This study showed that genetic polymorphisms of the ADD1, AGT and REN genes might be related to the hypertension in Korean adolescents. Conclusions : This study provided useful information on genetics markers related to blood pressure. Further study will be needed to confirm the effect of the alpha adducin gene, the angiotensinogen gene and the renin gene on essential hypertension.

Sequential anti-inflammatory and osteogenic effects of a dual drug delivery scaffold loaded with parthenolide and naringin in periodontitis

  • Rui Chen;Mengting Wang;Qiaoling Qi;Yanli Tang;Zhenzhao Guo;Shuai Wu;Qiyan Li
    • Journal of Periodontal and Implant Science
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    • v.53 no.1
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    • pp.20-37
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    • 2023
  • Purpose: Our pilot study showed that a 3-dimensional dual drug delivery scaffold (DDDS) loaded with Chinese herbs significantly increased the regenerated bone volume fraction. This study aimed to confirm the synergistic anti-inflammatory and osteogenic preclinical effects of this system. Methods: The targets and pathways of parthenolide and naringin were predicted. Three cell models were used to assess the anti-inflammatory effects of parthenolide and the osteogenic effects of naringin. First, the distance between the cementoenamel junction and alveolar bone crest (CEJ-ABC) and the bone mineral density (BMD) of surgical defects were measured in a rat model of periodontitis with periodontal fenestration defects. Additionally, the mRNA expression levels of matrix metallopeptidase 9 (MMP9) and alkaline phosphatase (ALP) were measured. Furthermore, the number of inflammatory cells and osteoclasts, as well as the protein expression levels of tumor necrosis factor-alpha (TNF-α) and levels of ALP were determined. Results: Target prediction suggested prostaglandin peroxidase synthase (PTGS2) as a potential target of parthenolide, while cytochrome P450 family 19 subfamily A1 (CYP19A1) and taste 2 receptor member 31 (TAS2R31) were potential targets of naringin. Parthenolide mainly targeted inflammation-related pathways, while naringin participated in steroid hormone synthesis and taste transduction. In vitro experiments revealed significant antiinflammatory effects of parthenolide on RAW264.7 cells, and significant osteogenic effects of naringin on bone marrow mesenchymal stem cells and MC3T3-E1 cells. DDDS loaded with parthenolide and naringin decreased the CEJ-ABC distance and increased BMD and ALP levels in a time-dependent manner. Inflammation was significantly alleviated after 14 days of DDDS treatment. Additionally, after 56 days, the DDDS group exhibited the highest BMD and ALP levels. Conclusions: DDDS loaded with parthenolide and naringin in a rat model achieved significant synergistic anti-inflammatory and osteogenic effects, providing powerful preclinical evidence.