• Title/Summary/Keyword: Metabolism Induction

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Effects of Korean traditional herbal formula for common cold on the activities of human CYP450 isozymes

  • Jin, Seong Eun;Ha, Hyekyung;Jeong, Soo-Jin;Shin, Hyeun-Kyoo
    • The Journal of Korean Medicine
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    • v.35 no.2
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    • pp.47-59
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    • 2014
  • Objectives: Most drug interactions are attributed to the inhibition or induction of the activity of cytochrome P450s (CYP450). Although the regulation of CYP450s by drugs has been widely reported, there have been few studies on influence of traditional herbal formulas on the drug-metabolizing enzymes. Because herbal formulas have been used traditionally to treat various diseases and because herb-drug interactions are crucial factors determining therapeutic efficacies, a systematic evaluation of the effects of herbal formulas is important. Methods: The effects of Galgeun-tang (GGT, gegen tang), Gumiganghwal-tang (GMGHT, jiuweiqianghuo tang), Insampaedok-san (ISPDS, renshenbaidu powder), Samsoeum (SSE, shensu drink), Socheongryong-tang (SCRT, xiaoqinglong-tang) and Sosiho-tang (SSHT, xiaochaihu tang) that are traditional herbal formulas used to treat common cold, on drug-metabolizing enzymes were evaluated through an in vitro CYP3A4, CYP2D6, CYP2C19 and CYP2E1 inhibition assay to assess its interaction potential with synthetic drugs. The inhibitory effects of herbal formulas were characterized with $IC_{50}$ values. Results: These six herbal formulas inhibited the activities of CYP3A4, 2C19, 2D6 and 2E1, in a concentration-dependent manner. Among the six herbal formulas, GGT critically inhibited CYP2C19, CYP2D6 and CYP2E1. GMGHT also inhibited CYP2D6 and CYP2E1 to a greater extent than the other CYP450 isozymes. Additionally, SSE and SSHT may change the effects of medicines that depend primarily on the CYP2C19 and CYP2E1 pathways. On the other hand, ISPDS and SCRT were not inhibited CYP3A4, CYP2C19, CYP2D6 and CYP2E1-mediated metabolism. Conclusions: These findings provide useful information regarding the safety and effectiveness of herbal formulas.

Environmental Genomics Related to Environmental Health Biomarker

  • Kim, Hyun-Mi;Kim, Dae-Seon;Chung, Young-Hee
    • Molecular & Cellular Toxicology
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    • v.2 no.2
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    • pp.75-80
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    • 2006
  • Biomarkers identify various stages and interactions on the pathway from exposure to disease. The three categories of biomarkers are those measuring susceptibility, exposure and effect. Susceptibility biomarkers are identifiable genetic variations affecting absorption, metabolism or response to environmental agents. Biomarkers of exposure indicate the amount of a foreign compound that is absorbed into the body. Biological measurements performed on human tissues are vastly expanding the capabilities of classical epidemiology, which has relied primarily on estimates of human exposure derived form chemical levels in the air, water, and other exposure routes. Biomarkers of exposure indicate the amount of a foreign compound that is absorbed into the body. Biological measurements performed on human tissues are vastly expanding the capabilities of classical epidemiology, which has relied primarily on estimates of human exposure derived form chemical levels in the air, water, and other exposure routes. The biomarker response is typical of chemical pollution by specific classes of compound, such as (i) heavy metals (mercury, cadmium, lead, zinc), responsible for the induction of metallothionein synthesis, and (ii) organochlorinated pollutants (PCBs, dioxins, DDT congeners) and polycyclic aromatic hydrocarbons (PAHs), which induce the mixed function oxygenase (MFO) involved in their bio transformations and elimination. Currently genomic researches are developed in human cDNA clone subarrays oriented toward the expression of genes involved in responses to xenobiotic metabolizing enzymes, cell cycle components, oncogenes, tumor suppressor genes, DNA repair genes, estrogen-responsive genes, oxidative stress genes, and genes known to be involved in apoptotic cell death. Several research laboratories in Korea for kicking off these Environmental Genomics were summarized.

Effect of Strontium on Polyamine Synthesis and Diamine Oxidase during the Germination of Mung Bean (Vigna radiata L.) (숙주의 발아과정 동안 폴리아민 생합성과 Diamine 산화효소에 대한 스트론티움 효과)

  • Kim, Tae-Wan;Kwon, Young-Up;Yun, Seung-Gil
    • Korean Journal of Soil Science and Fertilizer
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    • v.36 no.6
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    • pp.437-444
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    • 2003
  • Objective of this experiment was to investigate the role of strontium in intracellular processes in mung bean (Vigna radiata L.). Diamine oxidase (DAO) induction by $Sr^{2+}$ appeared to a decrease in putrescine levels correspondently. DAO activities in the hypocotyls were in a range of 0.5 to $1.8unit{\cdot}mg^{-1}\;protein{\cdot}min^{-1}$. The decrease in Put levels in the cotyledons might be partly resulted from Put degradation by DAO. It was observed that the accumulation of spermidine and spermine by $Sr^{2+}$ was in the range of 1 mM to 10 mM. Spermidine levels were 2 to 3 fold higher than in the absence of strontium. The increase in polyamine levels was observed not only on a basis of g fresh weight but also a RNA basis. These results demonstrated that the inhibitory action of $Sr^{2+}$ may be closely related with polyamine metabolism as well as diamine oxidation and polyamine accumulation.

Effect of Epigallocatechin-3-Gallate on the alveolar bone remodeling and arthritis in collagen-induced arthritis model in mice (콜라겐 유도 관절염 모델에서 동반된 치주염 유발시 EGCG가 치주염 치료에 미치는 효과에 관한 연구)

  • Cho, In-Woo;Yim, Seong-Jun;Shin, Hyun-Seung;Park, Jung-Chul
    • The Journal of the Korean dental association
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    • v.54 no.4
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    • pp.284-295
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    • 2016
  • The aim of this study was to evaluate the effect of Epigallocatechin-3-Gallate (EGCG) on the alveolar bone metabolism in a collagen-induced arthritis (CIA) model in mice to enhance the understanding of rheumatoid arthritis (RA)-associated alveolar bone loss. Following the induction of CIA in animals (mice, n=16), mandibles were retrieved for micro-computed tomography (micro-CT) and isolation of alveolar bone cells (ABCs). In vitro osteogenic potentials of ABCs were evaluated and the mRNA expression of downstream effector genes was assessed. CIA was successfully induced in all animals, and micro-CT data showed that alveolar bone loss was significantly increased in the CIA group while the treatment of EGCG prevented the alveolar bone resorption. Osteogenesis by ABCs was significantly increased in the CIA+EGCG group in vitro. The analysis of mRNA expressions showed that osteoclastogenesis-associated genes were increased in CIA group while bone protecting genes were upregulated in EGCG treated group. The results demonstrate that EGCG downregulated the alveolar bone resorption in a CIA model in mice, and upregulation of bone protecting genes appear to be involved. Further studies are warranted.

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The Effects of Artemisiae Capillaris, Ponciri Fructus and Cartaegi Fructus in Obese Rats Induced by High Fat Diet (고지방 식이로 유도된 비만 흰쥐에 인진(茵蔯), 지실(枳實), 산사가 미치는 영향)

  • Ban, Sang-Seok;Yoon, Hyeon-Deok;Shin, Oh-Chul;Shin, Yoo-Jung;Park, Chi-Sang;Park, Ji-Ha;Seo, Boo-Il
    • The Korea Journal of Herbology
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    • v.21 no.3
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    • pp.55-67
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    • 2006
  • Objectives : This study was designed in order to determine the effects of Artemisiae Capillaris, Ponciri Fructus and Cartaegi Fructus so as to care the obesity and obesity-related diabetes. Methods : After induction of obesity by high fat-diet in rats, the each extracts of three medicinal stuffs were administrated with continuous high fat-diet for 4 weeks. And the changes of lipid metabolism, liver function and blood levels of glucose and insulin were examined. Results : Blood concentrations of triglyceride, free fatty acid and LDL-cholestrol were increased in obese group compared with standard dieted group. By treatment of Ponciri Fructus or Cartaegi Fructus with high fat-diet, their concentrations of glyceride and free fatty acid were significantly decreased. Blood level of LDL -cholesterol was decreased in all stuffs treated groups, however atherogenic index was significantly decreased in treatment of Cartaegi Fructus with high fat-dieted group. Conclusion : High fat-dieted with treatment of Ponciri Fructus or Cartaegi Fructus, fatty degeneration was remarkably diminished.

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Bacillus cereus ASK-202에서 cloning 된 agarase의 물리 ${\cdot}$ 화학적 특성

  • Hwang, Seon-Hui;Ha, Sun-Deuk;Kim, Bong-Jo;Gong, Jae-Yeol
    • 한국생물공학회:학술대회논문집
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    • 2002.04a
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    • pp.534-537
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    • 2002
  • An agarase gene from Bacillus cereus ASK202 was expressed in high levels by E. coli BL21(DE3)/pEBA1 using pET28a(+) vector system with the inducible T7 promoter in the presence of isopropyl- ${\beta}$ -thiogalactopyranoside. The open reading frame encodes 761 amino acid residues with a calculated molecular weight of 83,300 daltons and a potential signal peptide about 36 amino acid residues at the N-terminus. E. coli BL21(DE3)/pEBA1 produce 1280 unit/ ${\ell}$ of agarase. The optimum physical condition for the agarase activity was pH 5.6, and $40^{\circ}C$, respectively. The agarase activity was stable up pH $4.0{\sim}9.0$ and $4{\sim}40^{\circ}C$. The km and maximum rate of metabolism for agar were 0.068mg/$m{\ell}$ and 0.094mg/$m{\ell}{\cdot}min$, respectively.

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Antiviral Activity of the Exopolysaccharide Produced by Serratia sp. Strain Gsm01 Against Cucumber Mosaic Virus

  • Ipper, Nagesh S.;Cho, Sae-Youll;Lee, Seon-Hwa;Cho, Jun-Mo;Hur, Jang-Hyun;Lim, Chun-Keun
    • Journal of Microbiology and Biotechnology
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    • v.18 no.1
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    • pp.67-73
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    • 2008
  • The potential of the exopolysaccharide (EPS) from a Serratia sp. strain Gsm01 as an antiviral agent against a yellow strain of Cucumber mosaic virus (CMV-Y) was evaluated in tobacco plants (Nicotiana tabacum cv. Xanthi-nc). The spray treatment of plants using an EPS preparation, 72h before CMV-Y inoculation, protected them against symptom appearance. Fifteen days after challenge inoculation with CMV-Y, 33.33% of plants showed mosaic symptoms in EPS-treated plants compared with 100% in the control plants. The EPS-treated plants, which showed mosaic symptoms, appeared three days later than the controls. The enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase polymerase chain reaction (RT-PCR) analyses of the leaves of the protected plants revealed that the EPS treatment affected virus accumulation in those plants. Analysis of phenylalanine ammonia lyase, peroxidase, and phenols in protected plants revealed enhanced accumulation of these substances. The pathogenesis-related (PR) genes expression represented by PR-lb was increased in EPS-treated plants. This is the first report of a systemic induction of protection triggered by EPS produced by Serratia sp. against CMV-Y.

Chiisanoside, A Lupane Triterpenoid from Acanthopanax Leaves, Stimulates Proliferation and Differentiation of Osteoblastic MC3T3-E1 Cells

  • Choi, Eun-Mi;Ding, Yan;Nguyen, Huu Tung;Park, Sang-Hyuk;Nguyen, Xuan Nhiem;Liang, Chun;Lee, Jung-Joon;Kim, Young-Ho
    • Natural Product Sciences
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    • v.14 no.1
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    • pp.21-26
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    • 2008
  • The leaves of Acanthopanax species have traditionally been used as a tonic and a sedative as well as in the treatment of rheumatism and diabetes. Chiisanoside is the major active lupane triterpenoid of Acanthopanax leaves. To investigate the bioactivities of chiisanoside, which act on bone metabolism, the effects of chiisanoside on the function of osteoblastic MC3T3-E1 cells were studied. Chiisanoside $(0.02{\sim}20\;{\mu}M)$ significantly increased the growth of MC3T3-E1 cells and caused a significant elevation of alkaline phosphatase (ALP) activity, collagen content, and nodules mineralization in the cells (P < 0.05). The effect of chiisanoside (2 ${\mu}M$) in increasing ALP activity was completely prevented by the presence of tamoxifen, suggesting that the effect of chiisanoside might be partly estrogen receptor mediated. Moreover, cotreatment of p38 inhibitor SB203580 or JNK inhibitor SP600125 inhibited chiisanoside-mediated ALP upregulation, suggesting that the induction of differentiation by chiisanoside is associated with increased activation of p38 and JNK mitogen-activated protein kinases. Our data indicate that the enhancement of osteoblast function by chiisanoside may result in the prevention for osteoporosis.

Potentiation of Carbon Tetrachloride Hepatotoxicity induced by Repeated Physical Exercise in adult Female rats (백서의 반복적인 육체운동에 의한 사염화탄소 간독성의 증폭효과)

  • Kim, Su-Nyeon;Kim, Young-Chul
    • Toxicological Research
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    • v.8 no.2
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    • pp.265-272
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    • 1992
  • Effects of repeated physical exercise on the carbon tetrachloride ($CCl_4$) hepatotoxicity were examined in adult female rats. Rats were introduced into a cylindrical rotating cage and forced to exercise for 1 hr each day, 6days/week, for 5 consecutive weeks at a speed starting from 10m/min, increased by 1m/min per day until the speed reached 27m/min. Significantly less body weight gain was observed in the exercise group suggesting that physical fitness had been induced in these animals. Eighteen hours following termination of the last exercise bout rats were treated with $CCl_4$(2 mmol/kg.ip). The $CCl_4$-induced heptotoxicity was significantly potentiated in the repeated exercise group compared to the resting sedentary animals as determined by changes in serum sorbitol dehydrogenase (SDH), glutamic oxaloacetic transaminase(GOT), glutamic pyruvic transaminase (GPT), and glucose-6-phosphatase(G-6-Pase) activities when measured 24hrs following the $CCl_4$ treatment. Hepatic drug metabolizing activity was determined in order to elucidate the underlying mechanism of potentiating action of the $CCl_4$ hepatotoxicity induced by repeated physical exercise. Repeated exercise increased the hepatic microsomal cytochrome P-450 contents and aminopyrine N-demethylase activity. The results suggest that the potentiation of $CCl_4$ hepatotoxicity by repeated exercise is associated with induction of the mixed function oxidase (MFO) enzyme system mediating the metabolism of $CCl_4$ to its active metabolite(s).

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Comparative Investigation of Glutathione S-Transferases, Glyoxalase-I and Alliinase Activities in Different Vegetable Crops

  • Hossain, Md Daud;Rohman, Md Motiar;Fujita, Masayuki
    • Journal of Crop Science and Biotechnology
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    • v.10 no.1
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    • pp.19-26
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    • 2007
  • Glutathione S-transferases(GSTs, EC 2.5.1.18), glyoxalase-I(EC 4.4.1.5) and alliin lyase(alliinase, EC 4.4.1.4) are important enzyme systems in plant bodies. The first two are mainly detoxifying enzymes that utilize glutathione(GSH) in the defense mechanism, and the last one is mainly involved in secondary metabolism and relevant to sulfur compounds derived from GSH. The activities of the three enzymes have been investigated in soluble extracts of vegetable crops, including pumpkin, cabbage, broccoli, radish, carrot, potato, sweet potato, mungbean, and onion. GST activities were detected in all of the vegetables, and the extract of onion bulb exhibited the highest specific activity(648 nmol/min/mgP). The putative GSTs of most of the vegetables were found to be induced by ethanol. The activities of GSTs in onion bulb were found to be markedly inhibited by S-hexyl glutathione and were also inhibited by S-butyl glutathione and S-propyl glutathione. The anti-CmGSTF1 antiserum recognized a thick band for putative onion GST. The estimated glyoxalase-I activity level was also high in onion bulb(4540 nmol/min/mgP), indicating that the thick band detected by Western blot analysis might result from partial recognition of glyoxalase-I by the antiserum. The specific activities for glyoxalase-I were moderate in radish and carrot, and the extracts of other vegetables had rather low levels of activities. The extract of onion also showed the highest specific activity level for alliinase(2069nmol pyruvate/mgP). The extracts of other vegetables also had alliinase activities, although the estimated values were much lower than that of onion.

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