• Title/Summary/Keyword: cytochrome P450s

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Effects of Boganhwan Decoction on the Liver Lipid Peroxide Content and Metabolic Enzyme System (노화과정(老化過程)의 흰쥐에서 보간환(補肝丸)이 간장(肝臟)의 대사효소계(代謝酵素系)에 미치는 영향(影響))

  • Cho, Han-sook;Oh, Min-suk;Song, Tae-won
    • Journal of Haehwa Medicine
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    • v.8 no.1
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    • pp.711-726
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    • 1999
  • Aging in the life form occurs due to a gradual progression of the body growth and degeneration. Morphological and functional changes in the body decreases the adaptation and prevention capacity leading into the decline of a life force. Various studies have been released to examine the anti-aging effects of herbal prescriptions. This experiment has chosen Boganhwan which is used for the deficiency of the liver function and studied the anti-aging factors by examining the biotransformation enzymes. The following results were obtained in this study: 1. Hepatic lipid peroxide activity was significantly suppressed in the experimental group treated with Boganhwan for 2 weeks at the dosage of 350mg/kg, while other dosage groups did not present much changes. 2. Insignificant changes were shown for the cytochrome P-450 level, aminopyrine demethylase, and aniline hydroxylase (AH) activities. Cytochrome P-450 do not appears to be a part of the detoxification scheme. 3. Boganhwan decoction treated group showed most significant increase of superoxide dismutase (SOD), catalase, superoxide, and glutathione activities at the concentration of 350mg/kg and 500mg/kg. 4. Glutathione S-transferase and glutathione made most significant increase at the decoction concentration of 350mg/kg and 500mg/kg compared to the control group. 5. Hepatic glutathione concentration, protein bound-SH, and nonprotein bound-SH made most significant increase at the decoction concentration of 350mg/kg and 500mg/kg compared to the control group. From the above results, Boganhwan decoction played an important role in eliminating foreign substances in the body excluding cytochrome P-450 enzyme system. Thus, Boganhwan decoction can provide substantial aid in preventing and treating senile related illnesses.

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In Vitro Inhibitory Effect of Licoricidin on Human Cytochrome P450s

  • Kim, Sunju;O, Heungchan;Kim, Jeong Ah;Lee, Seung Ho;Lee, Sangkyu
    • Mass Spectrometry Letters
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    • v.5 no.3
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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.

Cancer Chemopreventive Potential of Scenedesmus spp. Cultured in Medium Containing Bioreacted Swine Urine

  • Shon, Yun-Hee;Nam, Kyung-Soo;Kim, Mi-Kyung
    • Journal of Microbiology and Biotechnology
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    • v.14 no.1
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    • pp.158-161
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    • 2004
  • Scenedesmus spp. were cultured for 51 days in newly developed medium, KEP I (Kim and Ecopeace: initials of corresponding author and environmental company) made with Bacterio-Mineral-Water (3%, v/v) that had been bio-reacted with swine urine medium to 10% (v/v) Bold's Basal medium, and investigated for cancer chemopreventive potential by measuring the induction of quinone reductase (QR), glutathione S-transferase (GST), and reduced glutathione (GSH), and inhibition of cytochrome P450 (CYP) 1A1 activity. The activitives of QR and GST of Scenedesmus spp. cultured in KEP I medium were increased by 3.0-fold and 1.5-fold, respectively. However, Scenedesmus spp. cultured in control medium (CT) increased the activitives of QR and GST by 1.8-fold and 1.3-fold, respectively. Scenedesmus spp. in KEP I medium strongly inhibited CYP 1Al activity. These results show that Scenedesmus spp. in KEP I medium has cancer chemopreventive potential and may be a candidate for further development as a chemopreventive agent.

ROLES OF HUMAN LIVER CYTOCHROMES P450 3A4 AND 1A2 IN THE OXIDATION OF MYRISTICIN

  • Yun, Chul-Ho;Lee, Hye-Suk;Lee, Hee-Yong;Yim, Sung-Kun;Kim, Keon-Hee;Yea, Sung-Su
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.137.1-137.1
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    • 2003
  • Myristicin, 1-allyl-3, 4-methylenedioxy-5-methoxybenzene, is a naturally occurring alkenylbenzene compound. It is found in nutmag, mace, parsley, carrot, black pepper, many natural oils and flavoring agents. The aim of this work was to identify the form(s) of human liver cytochrome P450 (P450) involved in the hepatic transformation of myristicin to its major metabolite, 5-allyl-1-methoxy-2, 3-dihydroxybenzene (M1). (omitted)

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The Anti-hepatotoxic Effect of Ginseng in Rats: Meta-analysis

  • Kook, Se-Jeong;Han, Hye-Kyoung;Kim, Gun-Hee;Choi, Ki-Heon
    • Journal of Ginseng Research
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    • v.32 no.2
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    • pp.161-170
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    • 2008
  • The aim of this meta-analysis was to systematically investigate the anti-hepatotoxic effect of ginseng in rats induced toxicity which damage to liver. Primary researches were gained on the ScienceDirect database, the DBpia, and the KISS, and the data about the effect factors in plasma and in enzyme were listed as many as possible. The effect factors were alanine transaminase (ALT), aspartate transaminase (AST), liver aminopyrine N-demethylase (AD), liver aniline hydroxylase (AH), liver 3,4-Methylenedioxyamphetamine (liver MDA), cytochrome P450 (P450), serum alkaline phosphatase (ALP), serum lactate dehydrogenase (LDH), cytochrome b5 (Cyto b5), glutathione reductase (GR), Liver glutathione S-transferase (GST), liver glutamyltransferase (GT), Liver (${\gamma}-GCS$), serum liver 3,4-Methylenedioxyamphetamine (serum MDA), serum sorbitol dehydrogenase (SDH), serum total protein (TP), serum ${\gamma}-glutamyltransferase$ (${\gamma}-GT$). To investigate the effect of ginseng, the mean difference (MD) between the group of rats induced by toxicity (RH) and the group of rats induced by toxicity with ginseng (RHG) were combined, and the significance of MDs were tested. The combined MDs were checked the biases caused by heterogeneity among studies and the publication biases, and adjusted by using random effect model and trim and fill method, respectively. The effect about ALT, AST, ALP, LDH, SDH, TP and ${\gamma}-GT$ in plasma factors were significant, and about AD, liver MDA, P450, Cyto b5, GR, GST, GT and ${\gamma}-GCS$ in enzyme factors were significant. The treatment with ginseng supplementation was significantly effected on plasma and enzyme factors of damaged-rats.

Effects of Tributyltin Chloride (TBTCI) on Reproductive Organs and Steroidogenic Enzymes

  • Ki, Ho-Youn;Lee, Su-Jung;Shin, Jae-Ho;Kang, Il-Hyun;Moon, Hyun-Ju;Kim, Tae-Sung;Hoon Bae;Dong, Mi-Sook;Yoon, Yong-Dal
    • Proceedings of the Korean Society of Developmental Biology Conference
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    • 2003.10a
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    • pp.67-67
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    • 2003
  • Tributyltin chloride (TBTCI) is an organotin compounds that have been widely used as antifouling agents and bioaccumulated in the food chain. TBTCI has been known to induce imposex in female gastropods. There are several reports that TBTCI increased testosterone level and inhibited the conversion of testosterone to estradiol by the aromatase cytochrome P450 enzyme. In this studies, we investigated the effects of TBTCI on steroidogenesis in testes, We dosed to 4-week-old Spragus-Dawleys (SD) male rats with TSTCI (0, 1, 5, 10, and 20mg/kg/day) daily by gavage for 14 days. TBTCI significantly decreased the weights of seminal vesicle, prostate, cowper's gland and LABC at 10 and 20mg/kg/day but significantly Increased the weights of liver at 10 and 20mg/kg/day and adrenals at 20mg/kg/day. mRNA levels of steroidogenic acute regulatory (StAR) and P450 aromatase were decreased and mRNA levels of cytochrome P450 17$\alpha$-hydroxylase/$C_{17-20}$ lyase (P450c17) were increased by TBTCI. TBTCI significantly increased serum testosterone level in dose-dependent manner. From above results, we found that TBTCI altered mRNA levels of enzymes related steroidogenesis, weights of organs and serum testosterone levels. This suggests that change of hormone levels may be due to alteration of mRNA levels of steroidogenic enzyme in testes, but further studies are necessary to investigate hormone levels in testis organ in order to find a relation of enzyme related to steroidogenesis with hormone levels. This work was supported by the Korea FDA Grant KFDA-03131-EDS-010.

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Effect of TSHAC on Human Cytochrome P450 Activity, and Transport Mediated by P-Glycoprotein

  • Im, Yelim;Kim, Yang-Weon;Song, Im-Sook;Joo, Jeongmin;Shin, Jung-Hoon;Wu, Zhexue;Lee, Hye Suk;Park, Ki Hun;Liu, Kwang-Hyeon
    • Journal of Microbiology and Biotechnology
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    • v.22 no.12
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    • pp.1659-1664
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    • 2012
  • TSAHC [4'-(p-toluenesulfonylamido)-4-hydroxychalcone] is a promising antitumorigenic chalcone compound, especially against TM4SF5 (four-transmembrane L6 family member 5)-mediated hepatocarcinoma. We evaluated the potential of TSAHC to inhibit the catalytic activities of nine cytochrome P450 isoforms and of P-glycoprotein (P-gp). The abilities of TSAHC to inhibit phenacetin O-deethylation (CYP1A2), coumarin 6-hydroxylation (CYP2A6), bupropion hydroxylation (CYP2B6), amodiaquine N-deethylation (CYP2C8), diclofenac 4-hydroxylation (CYP2C9), omeprazole 5-hydroxylation (CYP2C19), dextromethorphan O-demethylation (CYP2D6), chlorzoxazone 6-hydroxylation (CYP2E1), and midazolam 1'-hydroxylation (CYP3A) were tested using human liver microsomes. The P-gp inhibitory effect of TSAHC was assessed by [$^3H$]digoxin accumulation in the LLCPK1-MDR1 cell system. TSAHC strongly inhibited CYP2C8, CYP2C9, and CYP2C19 isoform activities with $K_i$ values of 0.81, 0.076, and $3.45{\mu}M$, respectively. It also enhanced digoxin accumulation in a dose-dependent manner in the LLCPK1-MDR1 cells. These findings indicate that TSAHC has the potential to inhibit CYP2C isoforms and P-gp activities in vitro. TSAHC might be used as a nonspecific inhibitor of CYP2C isoforms based on its negligible inhibitory effect on other P450 isoforms such as CYP1A2, CYP2A6, CYP2B6, CYP2D6, CYP2E1, and CYP3A.