• Toxicological Research
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• 제32권3호
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• pp.207-213
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• 2016

Although propolis is one of the most popular functional foods for human health, there have been no comprehensive studies of herb-drug interactions through cytochrome P450 (CYP) inhibition. The purpose of this study was to determine the inhibitory effects of propolis on the activities of CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1 and 3A4 using pooled human liver microsomes (HLMs). Propolis inhibited CYP1A2, CYP2E1 and CYP2C19 with an $IC_{50}$ value of 6.9, 16.8, and $43.1{\mu}g/mL$, respectively, whereas CYP2A6, 2B6, 2C9, 2D6, and 3A4 were unaffected. Based on half-maximal inhibitory concentration shifts between microsomes incubated with and without nicotinamide adenine dinucleotide phosphate, propolis-induced CYP1A2, CYP2C19, and CYP2E1 inhibition was metabolism-independent. To evaluate the interaction potential between propolis and therapeutic drugs, the effects of propolis on metabolism of duloxetine, a serotonin-norepinephrine reuptake inhibitor, were determined in HLMs. CYP1A2 and CYP2D6 are involved in hydroxylation of duloxetine to 4-hydroxy duloxetine, the major metabolite, which was decreased following propolis addition in HLMs. These results raise the possibility of interactions between propolis and therapeutic drugs metabolized by CYP1A2.

• 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.

• 생약학회지
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• 제33권1호통권128호
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• pp.35-41
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• 2002

The MeOH ext., $CH_2Cl_2$ Frac., EtOAc Frac., n-BuOH Frac., and $H_2O$ Frac. of 23 Korean medicinal herbs were prepared and were tested the inhibitory effects on Cytochrome P450 (Cyp) 1A1/2, 2B1/2, 2E1. Among the tested samples, the extracts of Selaginella tamariscina, Euonymus alatus, Salvia miltiorhiza, Angelica acutiloba, Rheum palmatum, Paeonia moutan, Scutellaria barbata, Tribulus terrestris, Hedyotis diffusa, Curcuma zedoaria, Rehmania glutinosa, Trogopterus xanthipes, Melandryum firmum, Achyranthes bidentata, Leonurus sibricus, Panax ginseng, Paeonia lactiflora, Poncirus trifoliata, Cnidium officinale, Cyperus rotundus, Corydalis ternata showed significant inhibitory effects on Cyp 1A1/2, 2B1/2, 2E1. The $IC_{50}$ values of those extracts were found to be below $50\;{\mu}g/ml$.

• 사상체질의학회지
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• 제24권4호
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• pp.84-91
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• 2012

Objectives : The purpose of this study is to investigate the inhibitory or inductive potentials of Yuldahanso-tang (YDT) and Chungsimyonja-tang (CST), herbal formulas for Taeeumin, on cytochrome P450 (CYP450) drug metabolizing enzyme. The mechanisms for the herbal formula-drug interaction has not been well reported in spite of the chance for co-administration with conventional drugs. Methods : To evaluate the interaction potential of YDT-drug or CST-drug, the fluorescence-based enzyme assays on CYP450 isozymes including CYP3A4, CYP2C19, CYP2D6 and CYP2E1 were established in vitro. The inhibitory effects of herbal formulas were characterized with $IC_{50}$ values. Results : YDT showed inhibitory effects on CYP2D6 and CYP2E1-mediated metabolism, while it exhibited week inhibition on CYP3A4 and CYP2C19 relatively. CST exerted relatively weak inhibitory effects on the four CYP450 isozymes compared to that of YDT. Conclusions : These results suggest that the herbal formula-drug interaction could be occur when YDT are co-administered with drugs mediated by CYP2D6 or CYP2E1.

• Journal of the Korean Wood Science and Technology
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• 제39권6호
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• pp.469-480
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• 2011

본 연구에서는 Ceriporia sp. ZLY-2010을 이용하여 폴리염화비페닐류의 생분해와 효소 시스템간의 상관관계에 대해 알아보고자 하였다. 폴리염화비페닐 동족체 첨가에 따라 단백질 정량 및 manganese peroxidase (MnP)와 laccase의 활성을 비교하였으며, cytochrome P450 monooxygenase의 저해 정도를 평가함으로써 균체 내 효소가 폴리염화비페닐의 생분해에 끼치는 영향을 구명하였다. 단백질 정량 및 균체 외 효소 활성을 측정해 본 결과, 대조구에 비해 폴리염화비페닐 동족체를 첨가한 실험구에서 단백질 농도 및 효소활성이 더 높게 측정되었다. 단백질 농도의 경우, 2,2',4,4',5,5'-hexachlorobiphenyl을 첨가했을 때, 가장 높은 단백질 농도가 측정되었다. 하지만 MnP와 laccase 활성에서는 상대적으로 염소원자가 적게 치환된 2,3',4',5-tetrachlorobiphenyl을 첨가한 실험구에서 높게 나타나는 경향을 보였다. Cytochrome P450 monooxygenase의 저해 정도를 평가한 결과, 2,3',4',5-tetrachlorobiphenyl을 첨가한 실험구의 경우, 배양 1일째, 저해제 1-aminobenzotriazole 0.1 mM에서 2.73%의 분해율을 나타냈으며, 저해제 첨가 시 생분해율이 크게 감소하는 것으로 나타났다. 2,2',4,4',5,5'-hexachlorobiphenyl 역시, 저해제의 존재 하에 20% 내외의 분해율을 보였으며, 이는 대조구에 비해 약 40% 감소한 비율이다.

• 한국식품영양과학회지
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• 제27권4호
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• pp.712-717
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• 1998

This study was undertaken to investigate the inhibition effects of Auricularia auricula-judae methanol extract in edible mushroom on lipid peroxidation and liver damage in benzo(a)pyrene(B(a)P)-treated mice. The activities of serum aminotransferase, cytochrome P-450, superoxide dismutase, catalase, glutathione peroxidase and the hepatic content of lipid peroxide after B(a)P-treatment was markedly increased than control but those levels were significantly decreased by the treatment of Auricularia auricula-judae methanol extract. Glutathione S-transferase activity and the hepatic glutathione content were decreased by B(a)P-treatment than control, but those were also inhibited by the treament of Auricularia auricula-judae methanol extract. These results suggest that Auricularia auricula-judae methanol extract have a protective effect on liver damage by B(a)P.

• 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.

• 생명과학회지
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• 제8권5호
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• pp.604-613
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• 1998

담배의 phytoalexin으로 알려진 capsidiol 생합성의 마지막 단계에 관여하는 5-epi-aristolochene hydroxy-lase 유전자의 일부를 RT-PCR 방법으로 클로닝하였다. 클로닝한 CYP-B3는 콩, 완두 등의 cytochrome P450계의 유전자와 높은 동일성을 보였으며 heme 결합부위로 알려진 FxxGxRxCxG을 포함하고 있는 것으로 나타났다. 또한 CYP-B3는 저온, 고온 또는 제초제 등에 의해서는 유도되지 않고 Elicitor에 의해서만 특이하게 유도되는 것으로 나타나 Phytoalexin 생합성에 관여하는 유전자임을 확인하였다. Cyt P450 억제제인 ancy-midol과 ketoconazol에 의해 CYP-B3의 전사는 억제되지 않는 반면 5-epi-aristolochene hydroxylase의 효소활성은 현저히 억제되는 것으로 나타나 이들 억제제는 전사후의 효소의 합성 또는 활성을 억제하는 것으로 나타났다.

• 대한약학회:학술대회논문집
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• 대한약학회 2001년도 Proceedings of the Pharmaceutical Society of Korea
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• pp.168.2-169
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• 2001

• Biomolecules & Therapeutics
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• 제22권2호
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• pp.155-160
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• 2014

Thelephoric acid is an antioxidant produced by the hydrolysis of polyozellin, which is isolated from Polyozellus multiplex. In the present study, the inhibitory effects of polyozellin and thelephoric acid on 9 cytochrome P450 (CYP) family members (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4) were examined in pooled human liver microsomes (HLMs) using a cocktail probe assay. Polyozellin exhibited weak inhibitory effects on the activities of all 9 CYPs examined, whereas thelephoric acid exhibited dose- and time-dependent inhibition of all 9 CYP isoforms ($IC_{50}$ values, $3.2-33.7{\mu}M$). Dixon plots of CYP inhibition indicated that thelephoric acid was a competitive inhibitor of CYP1A2 and CYP3A4. In contrast, thelephoric acid was a noncompetitive inhibitor of CYP2D6. Our findings indicate that thelephoric acid may be a novel, non-specific CYP inhibitor, suggesting that it could replace SKF-525A in inhibitory studies designed to investigate the effects of CYP enzymes on the metabolism of given compounds.