• 제목/요약/키워드: CYP450 1A1

검색결과 314건 처리시간 0.039초

양격산화탕과 태음조위탕 추출물의 in vitro CYP450 효소 활성 억제 효과 (In vitro inhibitory effects of Yangguksanhwa-tang and Taeumjowi-tang on CYP450 isozymes)

  • 하혜경;진성은;신현규
    • 대한예방한의학회지
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    • 제16권3호
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    • pp.129-137
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    • 2012
  • Objective : Herb-drug interactions have become an important issue because of the consumption of herbal remedies has increased in the world. Yangguksanhaw-tang (Liang ge san huo-tang) and Taeumjowi-tang (Tai yin tiao wei-tang) are typical herbal formulas on Sasang constitution medicine (four-constitution medicine). This study was aimed at evaluating the effects of Yangguksanhaw-tang and Taeumjowi-tang on drug metabolizing enzymes, cytochrome P450 (CYP450) isozymes. Methods : Vivid$^{(R)}$ CYP450 Screening Kits were used to measure of CYP3A4, CYP2C19, CYP2D6 and CYP2E1 activities. This method is based on the use of fluorescent CYP450 substrates that are efficiently metabolized by specific CYP450 isozymes to yield a product with altered fluorescent properties. The percent inhibitions of CYP450s by herbal formulas were calculated. Results : Yangguksanhaw-tang inhibited CYP2C19 and CYP2E1 activities higher than that other CYP450 isozymes. The $IC_{50}$ values of CYP2C19 and CYP2E1 were 159.83 ${\mu}g/mL$ and 261.40 ${\mu}g/mL$, respectively. The CYP2E1 activity was inhibited ($IC_{50}=215.17{\mu}g/mL$) higher than that other CYP450 isozymes by Taeumjowi-tang. Conclusions : These results suggest that Yangguksanhaw-tang may inhibit the metabolism of co-administered drugs whose primary route of metabolism is via CYP2C19 or CYP2E1. Taeumjowi-tang could inhibit the metabolism of co-administered drugs, which are substrates for CYP2E1. Therefore, co-administration of the herbal formulas and other conventional drugs should be undertaken with care.

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
    • 대한한의학회지
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    • 제35권2호
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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.

수서 환경독성 평가와 어류 Cytochrome P450 1A (CYP1A) 유전자 (Assessment of Toxic Effects in Aquatic Environment and the Fish Cytochrome P450 1A(CYP1A) Gene)

  • 윤석주;김일찬;윤용달;이재성
    • 환경생물
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    • 제21권1호
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    • pp.1-7
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    • 2003
  • CYP1A 유전자는 cytochrome P450 약물대사효소에 속하며 다이옥신 등의 내분비계 장애물질에 의해 농도 의존적으로 유도되어 환경오염물질에 의해 유도되는 특성을 이용하여 환경오염물질에 대해 반응하는 생물체의 유전자 발현 변화뿐만 아니라 이를 토대로 특정지역의 환경오염에 관한 정보를 얻을 수 있다. 본 논문에서는 수서환경오염과 관련하여 CYP1A유전자의 유용성을 다각도로 논의하였다.

The Roles of Kupffer Cells in Hepatocellular Dysfunction after Femur Fracture Trauma in Rats

  • Lee, Woo-Yong;Lee, Sun-Mee
    • Archives of Pharmacal Research
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    • 제26권1호
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    • pp.47-52
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    • 2003
  • The aim of this study was to investigate the effects of trauma on alterations in cytochrome P450 (CYP 450)-dependent drug metabolizing function and to determine the role of Kupffer cells in hepatocellular dysfunction. Rats underwent closed femur fracture (FFx) with associated soft-tissue injury under anesthesia, while control animals received only anesthesia. To deplete Kupffer cells in vivo, gadolinium chloride (GdCl$_3$) was injected intravenously via the tail vein at 7.5 mg/kg body wt., 1 and 2 days prior to FFx surgery. At 72 h after FFx, serum alanine aminotransferase (ALT) activity was increased, and this increase was attenuated by GdCl$_3$ pretreatment. Serum aspartate aminotransferase (AST) and lipid peroxidation levels were not changed by FFx. Hepatic microsomal CYP 450 content and aniline p-hydroxylase (CYP 2E1) activity were significantly decreased; decreases that were not prevented by GdC1$_3$. The level of CYP 2B1 activity was decreased by Kupffer cell inactivation, but not by FFx. There were no significant differences in the activities of CYP 1A1, CYP 1A2 and NADPH-CYP 450 reductase among any of the experimental groups. Our findings suggest that FFx trauma causes mild alterations of hepatic CYP 450-dependent drug metabolism, and that Kupffer cells are not essential for the initiation of such injury.

Inhibition of 7-Alkoxyresorufin O-Dealkylation Activities of Recombinant Human CYP1A1 and CYP1B1 by Resveratrol

  • Dong, Mi-Sook;Chang, Suk-Kyung;Kim, Hyun-Jung;F. Peter Guengerich;Park, Young-In
    • 한국환경성돌연변이발암원학회지
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    • 제22권3호
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    • pp.169-174
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    • 2002
  • Resveratrol is known to have potent cancer chemopreventive activity against tumorigenesis caused by 7,12-dimetylbenz[$\alpha$]anthracene(DMBA) which is known to be oxidized to reactive products by cytochrome P450 1B1 (CYP1B1). The effects of resveratrol on the activity of recombinant human P450 1 family enzymes, expressed in Escherichia coli membranes with human NADPH-P450 reductase, were determined by measuring alkoxyresorufin O-dealkylation activity, e.g., ethoxyresorufin O-deethylation (EROD) CYP1A1, methoxyresorufin O-demethylation (MROD), CYP1A2, benzyloxyresorufin-O-debenzylation (BROD), CTP1B1. Resveratrol inhibited CYP1B1 and CYP1A1 activities in a dose-dependent manner with $IC_{50}$/ values of 59 and 10$\mu$M for EROD activity and 1.8 and 30$\mu$M for BROD activity, respectively. Resveratrol had only weak inhibitory effect on CYP1A2 activity ($IC_{50}$/ values of 0.44 mM for EROD and >2 mM for MROD). Furthermore, resveratrol did not affect NADPH-P450 reductase activity significantly. Resveratrol inhibited the CYP1B1-dependent EROD activity with a $K_{i}$ of 28 $\mu$M in a non-competitive type manner. these results suggest that resveratrol-derived inhibited of CYP1B1 and CYP1A1 activities may contribute to the suppression of DMBA inducible tumorigenesis observed in extrahepatic tissues.s.

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Bioactivation of Aromatic Amines by Human CYP2W1, An Orphan Cytochrome P450 Enzyme

  • Eun, Chang-Yong;Han, Song-Hee;Lim, Young-Ran;Park, Hyoung-Goo;Han, Jung-Soo;Cho, Kyoung-Sang;Chun, Young-Jin;Kim, Dong-Hak
    • Toxicological Research
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    • 제26권3호
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    • pp.171-175
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    • 2010
  • The human genome contains approximately 13 orphan cytochrome P450 (P450, CYP) genes, of which the apparent function or substrate has not been identified. However, they seem to possess their own biological relevance in some tissues or developmental stages. Here, we characterized the heterologously expressed CYP2W1, an orphan P450 enzyme. The recombinant CYP2W1 protein containing a $6{\times}$(His)-tag at Nterminus has been expressed in Escherichia coli and purified. Expression level of CYP2W1 holoenzyme was around 500 nmol P450 holoenzyme per liter culture medium. The reduced CO difference spectrum of CYP2W1 showed a maximum absorption at 449 nm. CYP2W1 indicated the significant induction to bioactivate Trp-P-1, MeIQ, and IQ in E. coli DJ701 tester strain. However, the bioactivation of B[$\alpha$]P, and NNK by CYP2W1 was relatively low. The model structure of CYP2W1 suggested the characteristic P450 folds with the lengths and orientations of the individual secondary elements. The F-G loop is situated on the distal side of heme to accommodate the flexibility of active site of CYP2W1. These studies can provide useful information for the finding of its biological roles and structure-function relationships of an orphan CYP2W1 enzyme.

뱀장어(Anguilla japonica)에서 Cytochrome P450 1 gene 클로닝 및 benzo[a]pyrene 노출에 따른 발현 분석 (Cytochrome P450 1 gene in Eel, Anguilla japonica: cloning and expression patterns after exposure to benzo[a]pyrene)

  • 조현호;김주안;이승현;정준기
    • 한국어병학회지
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    • 제33권2호
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    • pp.153-161
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    • 2020
  • Cytochrome P450(CYP) gene is involved in the biotransformation of drugs and environmental pollutants. In this study, we analyzed the nucleotide sequence of the Anguilla japonica CYP1(AjCYP1) family gene and examined the relative expression of AjCYP1A, AjCYP1B and AjCYP1C1 in response to the exposure to environmental pollutants. After exposure to B[a]P 20mg/kg bw, the expression of AjCYP1 family gene increased over time. Among four tissues examined (liver, spleen, gill and kidney), AjCYP1 family gene was expressed significantly in the kidney. Compared with the control group, AjCYP1A was expressed about 5-fold at 48 hr, AjCYP1B about 6-fold at 24 hr, and AjCYP1C1 about 4-fold at 24 hr. However, after exposure to B[a]P 200mg/kg bw, AjCYP1A did not change in all tissues. On the other hand, AjCYP1B was expressed at about 4-fold at 24 hr in the spleen and 4-fold at 48 hr in the gill. Finally AjCYP1C1 was expressed 3.7-fold and 4.3-fold in the spleen and kidneys at 48 hr, respectively. Taken together, our results suggest that the expression of AjCYP1 gene in eel tissues might be used as a useful tool to assess the exposure to environmental pollutants in aquaculture system.

홍삼 Ginsenoside의 Cytochrome P450 저해 활성 평가 (In vitro Assessment of Cytochrome P450 Inhibition by Red Ginseng Ginsenosides)

  • 류창선;신장현;신병찬;심재한;양현동;이성우;김봉희
    • 약학회지
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    • 제59권2호
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    • pp.49-54
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    • 2015
  • In the present study we evaluated comparative herb-drug interaction potential of red ginseng total powder, ginsenoside Rg1, and Rb1 by inhibition of CYP isoforms including CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4 using pooled human liver microsomes (HLMs). As measured by liquid chromatography-electrospray ionization tandem mass spectrometry, red ginseng total powder inhibited significantly activities of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and testosterone 6-beta hydroxylation by CYP3A4, but the $IC_{50}$ values were higher than $556{\mu}g/ml$. Activities of CYP2B6, CYP2C9, CYP2D6 and CYP3A4 were inhibited by ginsenoside Rb1. Also, activities of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and testosterone 6-beta hydroxylation by CYP3A4 were inhibited by ginsenoside Rg1. The $IC_{50}$ values of ginsenoside Rb1 and Rg1 were higher than $200{\mu}g/ml$. Based on $IC_{50}$ values against CYP isoforms, ginsenosides-drug interactions by CYP inhibition may be very low in clinical situations.

인체 간 Microsome에서 우슬 추출물의 Cytochrome P450 약물 대사효소에 대한 억제작용 (The Inhibitory Effect of Achyranthes bidentata radix Extracts on Cytochrome P450-Catalyzed Reactions in Human Liver Microsomes)

  • 김경아;이지숙;박히준;김진우;김창주;심인섭;한승무;임사비나
    • 대한한의학회지
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    • 제24권2호
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    • pp.40-46
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    • 2003
  • Objectives : Achyranthes bidentata radix (Usul) has been used as anti-arthritic, antiallergic, antidiuretic, and so on. Recently extracts of Achyranthes bidentata radix have shown anti-inflammatory and cancer preventive effects in vitro and in vivo. Methods : We therefore evaluated the inhibitory potential of ethanol extracts of Achyranthes bidentata radix on cytochrome P450 (CYP) isoforms-catalyzed reactions, which relate to causes of cancer and inflammation, including CYP1A2, CYP2C9, CYP2C19, CYP2E1, CYP2D6, CYP2C8, and CYP3A4, using human liver microsomal preparations. Results : The extracts showed weak or negligible inhibitory effects on CYP2C9-catalyzed (S)-warfarin 7-hydroxylation, CYP2C19-catalyzed S-mephenytoin 4-hydroxylation, and CYP2D6-catalyzed dextromethorphan O-demethylation with each IC50 over 1750 g/ml, respectively. However, it showed relatively significant inhibitory effect on CYP1A2-catalyzed phenacetin O-deethylation and CYP2E1-catalyzed chlorzoxazone 6-hydroxylation with IC50s of 970.5 g/ml and 821.4 g/ml, respectively. Conclusions : These results suggest that extracts of Achyranthes bidentata radix have inhibitory effects on CYP-catalyzed reactions, especiallyCYP1A2 and CYP2E1, in human liver microsomes. These effects appear to relate to anti-inflammatory and cancer prevention following decrease of reactive oxygen species formed by CYP, especially CYP1A2 and CYP2E1, by Achyranthes bidentata radix. However, further evaluation is necessary to demonstrate and to confirm its effects in human.

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Induction of Cytochrome P-450 Protein in Wounded Avocado Roots(Persea americana, Mill)

  • Joo, Eun-Young
    • Preventive Nutrition and Food Science
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    • 제2권4호
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    • pp.328-332
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    • 1997
  • The ripe fruit of Hass avocado contains one of the highest elvels of cytochrome P-450 protein found in the plant kingdom. To determine whether wounded roots of avocado contain P-450 protein, the roots of avocado were wounded by slicing, and then allowed to incubate in sealed plastic bags, in 0.4M mannitol, and in the solution to make protoplast preparation containing cellulysin and macerase during the specified times. The microsomal proteins were extracted from the samples, separated by SDS-PAGE, and then subjected to Western blot analysis using polyclonal antibodies which are generated against the CYP71A1 protein. wounded roots in sealed bags produced CYP71A1 within 6 hours after cutting, and those in 0.4M mannitol did not produce CYP71A1 even after 72 hours, but those in the protoplast preparation by cellulysin and macerase induced and produced CYP71A was induced in only 24 hours. These results indicate that CYP 71A1 plays a role for wound healing for root tissue o avocado, and would-inducible P-450 protein was not detected in the mannitol solution by preventing a synthesis of ethylene in a liquid state, but the softening of tissues by cellulysin and macerase to make protoplast preparation was involved in an activation of CYP 71A1 even in the liquid state.

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