• The Journal of Internal Korean Medicine
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• v.29 no.4
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• pp.846-855
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• 2008

Objects : The aim of this study was to investigate the influence of five herbal medicines on cytochrome P450 3A4 drug-metabolizing enzymes in human liver microsomes. Methods : To use human liver microsomes, an extract of five herbal medicines, which are Artemisia princeps Pampan, Sophora jeponica Linne, Panax notoginseng F. H. Chen, Lithospermum Erythrorhizon Sieb., and Cirsium maackii Maxim, which together are called Jihyulyak(止血藥, drugs for arresting bleeding, hemostatics), was co-incubated and measured for relative enzyme activity in incubation condition compared to ketoconazole, a representative inhibitor of CYP 3A4. Results : We showed that all five of the traditional herbal medicines had no inhibition effect of CYP 3A4 at 10, 20, 30, 40, and $50{\mu}g/ml$ doses in human liver microsomes, although Sophora japonica Linne(SJL) showed a little inhibition at about 81% inhibition rate of control. However, this result is not enough to prove that SJL has a CYP 3A4 inhibition effect. Moreover, we can't make sure that those rates had significant induction effect on CYP 3A4. Conclusions : The result of this study could support that those herbal medicines are safer than chemical drugs, even if this is the basic step to prove that result.

• Toxicological Research
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• v.26 no.1
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• pp.47-52
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• 2010

The Malassezia fungi are responsible for various human skin disorders including dandruff and seborrheic dermatitis. Of the Malassezia fungi, Malassezia globosa (M. globosa) is one of the most common in human scalp. The completed genome sequence of M. globosa contains four putative cytochrome P450 genes. To determine the roles of Malassezia P450 enzymes in the biosynthesis of ergosterol, we isolated MGL3996 gene from M. globosa chromosomal DNA by PCR. The MGL3996 gene encodes an enzyme of 616 amino acids, which shows strong similarity with known CYP52s of other species. MGL3996 gene was cloned and expressed in Pichia pastoris (P. pastoris) heterologous yeast expression system. Using the yeast microsomes expressing MGL3996 protein, a typical P450 CO-difference spectrum was shown with absorption maximum at 448 nm. SDS-PAGE analysis revealed a protein band of apparent molecular weight 69 kDa and Western blot with anti-histidine tag antibody showed that MGL3996 was successfully expressed in P. pastoris. Cloning and expression of a new P450 gene is an important step to study the P450 monooxygenase system of M. globosa and to understand the role of P450 enzymes in pathophysiology of dandruff.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.11a
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• pp.165-169
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• 1996

The cytochrome P450 (P450) proteins have been studied extensively because of their prominent roles as catalysts in the oxidations of drugs, carcinogens, steroids, alkaloids, vitamins, and other important chemicals (Guengerich, 1991). In the past decade the study of these enzymes has been advanced by the cloning of cDNAs and expression of the proteins in several heterologous vector systems. One approach that has been employed in this and other laboratories is expression in bacteria. To date at least 31 different mammalian P450s have been expressed in Escherichia coli-band systems (Guengerich et al., 1996). In most of these cases the N-terminus has been altered to facilitate better expression (Barnes et al., 1991).

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.186.1-186.1
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• 2003

Certain polycyclic aromatic hydrocarbons (PAHs) have been reported to induce cytochrome P450 (P450) 1A1 and 1A2. In the present studies, the effects of six well-known PAHs on the activities of hepatic and pulmonary P450 enzymes were investigated in male ICR mice. When mice were treated intraperitoneally with 3, 10 and 30 mg/kg of individual PAHs for 3 consecutive days, the activities of ethoxyresorufin- and methoxyresorufin-O-dealkylases were significantly and (omitted)

• BMB Reports
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• v.31 no.4
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• pp.391-398
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• 1998

In vitro effects of acetone, methanol, and dimethylsulfoxide (DMSO) on liver microsomal cytochrome P450 (P450) content, and P450-dependent arylhydrocarbon hydroxylase (AHH) and 7-ethoxycoumarin O-deethylase (ECOD) activities were studied in rats. Acetone at 1% (v/v) enhanced the content ofP450, assayed spectrally in 3-methylcholanethrene (MC)- and ${\beta}-naphthoflavone$ (BNF)-inducible microsomes by 18 and 7%, respectively. Methanol, up to 5% (v/v) applied, also showed enhancement effects on P450 content in liver microsomes from rats treated with phenobarbital (PB), MC, and BNF, as well as uninduced microsomes with similar but low strength. DMSO, however, did not show such enhancing effects at the ranges of the concentrations applied. AHH and ECOD activities in MC-inducible microsomes were also enhanced by acetone at 1%, which was in proportion to the increase in P450 content by the same concentration. However, the P450 content, and AHH and ECOD activities, were decreased by increasing the concentration of acetone. Methanol at the same concentration with acetone also enhanced ECOD activity but not AHH activity in MCinducible microsomes. The enhancing effect of acetone on the enzymes was negligible when the microsomes were pretreated with a specific monoclonal antibody of MC-inducible isozyme. The difference in the effects of these solvents on P450 system might be due to their different properties that cause the P450 active site to be exposed in milieu.

• Korean Journal of Medicinal Crop Science
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• v.10 no.1
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• pp.29-36
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• 2002

Epimedium koreanum Nakai(EKN) has traditionally been well-known as a herbal medicine for the promotion of stamina and the improving sexual activity of human in oriental countries including Korea and China. The aim of this study was to investigate the effect of dietary supplementation of EKN water-extract(0.025%,w/v) on age-related change of xenobiotic metabolizing system in rat liver. Long-term supply of the EKN extract to rats did not induce any discernible signs. However, the mass of liver and kidney were slightly increased by the dietary supplementation. Level of cytochrome P450, NADPH cytochrome P450 reductase, P450 dependent ethoxycoumarin O-deethylase benzphetamine N-demethylase and glutathione-S-transferase in liver were decreased with age, but, these activities in 24 months of age were declined more in rats supplied with EKN extract. Level of cytochrome b5 and NADH-cytochrome b5 reductase were also decreased with age, however, there was no significant difference between with and without EKN extract. These results indicate that long-term supplementation of EKN extract to rats from weaning to 24 months may be a burden on the liver function in old age, and may aggregate the decline of xenobiotic metabolizing enzymes activities in old age.

• Journal of the Korean Wood Science and Technology
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• v.39 no.6
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• pp.469-480
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• 2011

In this study, to determine the ligninase activity related to the PCBs degradation of Ceriporia sp. ZLY-2010, the protein contents and manganese peroxidase (MnP) and laccase activities during cultivation on shallow stationary culture (SSC) medium were observed. 4 PCB congeners were selected depending on the number of chlorine substituted on biphenyl. Furthermore, to examine the effects of cytochrome P450 monooxygenase, the inhibition of cytochrome P450 monooxygenase was evaluated by measuring the biodegradation rate when inhibitor such as 1-aminobenzotriazole was added. The extracellular protein contents were affected by PCB congeners in culture media. The total protein in the culture medium showed the biggest differences between the samples containing 2,2',4,4',5,5'-hexachlorobiphenyl and the control. On the other hand, MnP and laccase activity showed dominant increases within samples containing 4,4'-dichlorobiphenyl and 2,3',4',5-tetrachlorobiphenyl. Cytochrome P450 monooxygenase was inhibited by adding inhibitor, 1-aminobenzotriazole in low concentration. Only 2.73% of 2,3',4',5-tetrachlorobiphenyl was degraed on day 1, and biodegradation of 2,2',4,4',5,5'-hexachlorobiphenyl was inhibited as well, showing about 20% of biodegradation rate.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.312.3-313
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• 2002

Recently we have reported that various hydroxystilbenes show strong inhibition of human P450 1 activity. A series of synthetic trans-stilbene derivatives were prepared and their inhibitory potentials were evaluated with the bacterial membrane of recombinant human P450 1A1, 1A2 or 1B1 coexpressed with human NADPH-P450 reductase to find new candidates for cancer chemoprevention, Of the compounds tested. SY-021 (3.5-dimethoxyphenyl vinyl thiophene) exhibited a potent inhibition of human P450 181 with an IC$_{50}$ value of 2 nM. SY-021 also showed the inhibitrion of P450 1A1 with IC$_{50}$ value of 61 nM and P450 1A2 with IC$_{50}$ value of 11 nM. SY-021 showed 31-fold selectivity for P450 1B1 over P450 1A1 and 6-fold selectivity for P450 1B1 over 1A2. We have further investigated the inhibition kinetics of P450 1A1. 1A2 and 1B1 by SY-021. The modes of inhibition by SY-021were non-compeitive for all three P450 1 enzymes. Effect of preincubation with NADPH on inhibition of P450 1B1 by SY-021 was determined. These results suggest that SY-021 is one of the mostj potent inhibitor of human P450 1 enzymes and may be considered as a good candidate for a cancer chemopreventive agent in human

• Proceedings of the Korean Society of Applied Pharmacology
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• 2006.11a
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• pp.51-66
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• 2006

The field of cytochrome P450 pharmacogenomics has progressed rapidly during the past 25 years. Recently, conjugating enzymes including sulfotransferase, acetyltransferase, glucuronosyltransferase and glutathione transferase have been also extensively studied. All the major human drug-metabolizing P450 enzymes and some conjugating enzymes have been identified and cloned, and the major gene variants that cause inter-individual variability in drug response and are related to adverse drug reactions have been identified. This information now provides the basis for the use of predictive pharmacogenomics to yield drug therapies that are more efficient and safer. Today, we understand which drugs warrant dosing based on pharmacogenomics to improve drug treatment. It is anticipated that genotyping could be used to personalize drug treatment for vast numbers of subjects, decreasing the cost of drug treatment and increasing the efficacy of drugs and health in general. It is assumed that such personalized P450 gene-based treatment which is so-called tailor(order)-made drug therapy would be relevant for 10-20% of all drug therapy in the future.

• 한국약용작물학회:학술대회논문집
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• 2006.11a
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• pp.51-66
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• 2006

The field of cytochrome P450 pharmacogenomics has progressed rapidly during the past 25 years. Recently, conjugating enzymes including sulfotransferase, acetyltransferase, glucuronosyltransferase and glutathione transferase have been also extensively studied. All the major human drug-metabolizing P450 enzymes and some conjugating enzymes have been identified and cloned, and the major gene variants that cause inter-individual variability in drug response and are related to adverse drug reactions have been identified. This information now provides the basis for the use of predictive pharmacogenomics to yield drug therapies that are more efficient and safer. Today, we understand which drugs warrant dosing based on pharmacogenomics to improve drug treatment. It is anticipated that genotyping could be used to personalize drug treatment for vast numbers of subjects, decreasing the cost of drug treatment and increasing the efficacy of drugs and health in general. It is assumed that such personalized P450 gene-based treatment which is so-called tailor(order)-made drug therapy would be relevant for 10-20% of all drug therapy in the future.