• Environmental Mutagens and Carcinogens
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• v.22 no.3
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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.

• Journal of Oral Medicine and Pain
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• v.21 no.2
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• pp.331-349
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• 1996

Cytochrome P45O is an oxidase involved in oxidation of alcohol and is known to be an activator of carcinogen. The present study was performed to study the effect of alcohol and cold stress on the expression of Cytochrome P450 IIEl (CYPIIE1) In the liver and salivary glands in rats by an immunoblot analysis. Sixteen rats were divided into 4 groups; 1)rats belonging to group I were allowed to take 15%(v/v) ethyl alcohol as a drink ad libitum: 2)rats of group II were bathed in cold water for 30 sec twice a day (during the one-week experiment); 3)rats comprising group III were received alcohol and cold stress as described above; 4)rats of group IV were selected as a control. The rat were sacrificed at the end of the one-week experiment. The livers and parotid and submandibular salivary glands were removed and stored at -2$0^{\circ}C$ until use. The stored organs were homogenized for 10 sec and the supernatants were obtained by centrifugation. The proteins of the supernatants were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and subjected to Western blotting. The blotted membranes were incubated with polyclonal antibodies to CYPIIEI . The obtained results were as follows : 1. The expression of CYPIIEl was apparently negative in the liver and salivary glands of group IV, wheras its expression was marked in the experiment groups I, II. and III. 2. No difference in the expression of CYPIIEl in the liver and salivary glands was observed between the experiment groups I, II, and III. 3. Among the experiment groups, the expression of CYPIIE1 in the liver was much greater than in the salivary glands. The expression of CYPIIE1 in the submandibular gland was weakly positive but was greater than in the carotid gland.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.11a
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• pp.159-159
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• 2004

• The Korea Journal of Herbology
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• v.22 no.1
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• pp.53-61
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• 2007

Objectives: Our previous studies have clearly demonstrated that the scavenging activity of reactive oxygen species (ROS), protective effect of lipid peroxidation (LPO), and inhibition of cytochrome P450 isozymes (CYPs) from the Circium japonicum aqua-acupuncture solution (CJAS). But, Circium japonicum water extracted solution (CJWS) was weakly reported in cardiovascular diseases such as oxidative stress-mediated atherosclerosis or its value evaluated. Methods: CJWS was assessed to determine the mechanism of its scavenging activity of ROS and inhibitory effect of CYP 2E1. Results: CJWS exhibited a concentration-dependent scavenger of DPPH and superoxide anions radicals using different assay systems. In addition, CJWS showed dose-dependent free radical scavenging activity, including hydroxyl radicals, peroxynitrite, and nitric oxide. The CJWS was also found to be effective in protecting rat liver homogenate against LPO. Futhermore, the CJWS showed significant inhibition of CYP 2E1 induced by pyrazol in a rat liver microsome. Conclusion : ROS and CYPs may play a role in several diseases, such as cardiovascular disease and heart failure. Our study demonstrated that the CJWS has excellent scavenging activity of ROS. Hence, it is worthwhile to investigate the potential effectiveness of CJWS in preventing oxidative stress-mediated cardiovascular diseases.

• BMB Reports
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• v.39 no.4
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• pp.448-451
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• 2006

Chemopreventive and cytotoxic effect of genistein against human breast cancer cell lines was investigated. Genistein inhibited cell proliferation in estrogen receptor-positive (MCF-7) and estrogen receptor-negative (MDA-MB-231) human breast carcinoma cell lines. Cytochrome P450 (CYP) 1A1-mediated ethoxyresorufin O-deethylase (EROD) activity was inhibited by genistein in a concentrationdependent manner. Genistein significantly inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cyclooxy-genase-2 activity and protein expression at the concentrations of 10 (p < 0.05), 25 (p < 0.05) and 50 mM (p < 0.01). In addition, ornithine decarboxylase (ODC) activity was reduced to 53.8 % of the control after 6 h treatment with 50 mM genistein in MCF-7 breast cancer cells. These results suggest that genistein could be of therapeutic value in preventing human breast cancer.

• Journal of Society of Preventive Korean Medicine
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• v.7 no.2
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• pp.65-74
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• 2003

Objective : The aim of present study is to evaluate the inhibitory potential of licorice extract and glycyrrhizin on cytochrome P450(CYP) in human liver microsomes. Methods : Using human liver microsomes, water extract of licorice and glycyrrhizin as an inhibitor were co-incubated with each probe drug representing selective CYP isoform activity. We measured relative metabolic activity in incubation condition compared to that with no extract of licorice using HPLC system. Results : Both water extracts of licorice and glycyrrhizin showed inhibitory effect on CYP-catalyzed reactions. CYP2C19 $(IC_{50}=126.7{\mu}g/ml)$ is most potently inhibited by water extract than other tested CYP isoforms$(IC_{50}>450{\mu}g/ml)$, but glycyrrhizin exhibited potent inhibition on CYP1A2$(IC_{50}=106.9{\mu}g/ml)$ followed by CYP2C9 and CYP2D6. Conclusion: These results indicate that water extract of licorice and glycyrrhizin have inhibitory potential on CYP-catalyzed reaction in human liver microsomes. But the mechanism of inhibition was slightly different between them Water extract of licorice mainly inhibited CYP2C19, and glycyrrhizin primarily inhibited CYP1A2. The inhibition by water extract of licorice and glycyrrhizin on CYP isoforms may cause drug interaction with co-administered drug leading to toxicity or treatment failure.

• Journal of Yeungnam Medical Science
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• v.3 no.1
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• pp.103-110
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• 1986

Cytochrome P-450(CP-450) is one of the three components of the liver microsomal enzyme system which hydroxylates fatty acids, hydrocarbons and a variety of drugs and other foreign compounds. Female Balb/c mice were immunized with purified polychlorinated bipheny(PCB)-induced CP-450 LMII. The spleen cells derived from immunized mice were fused with $SP^2$ myeloma cells using polyethylene glycol(PEG 3500). The hybrid cells were selected by hypoxanthine-aminopterine and thymidine(HAT) medium and the culture fluid were screened by enzyme-linked immunosorbent assay to CP450 LMII. The hybrid cess(${\times}10^7$) were innoculated into intraperitoneal cavity of Balb/c mice for the purpose of production of ascitic fluids. Monoclonal antibody(Mab) was purified from ascitic fluid by DEAE cellulose ion exchange chromatography and $I^{125}$-labeled Mab was also confirmed by autoradiography and SDS-polyacrylamide gel electrophoresis (MW : 55,000 and 110,000).

• Mass Spectrometry Letters
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• v.3 no.4
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• pp.104-107
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• 2012

Mollugin isolated from Rubia cordifolia is known to have anti-inflammatory, anti-cancer, and anti-viral activities. In the present study, a cocktail probe assay and LC-MS/MS were used to investigate the modulating effect of mollugin on cytochrome P450 (CYP) enzymes in male ICR mice. After mollugin was orally administrated to mice at the 20, 40, or 80 mg/kg for 3 days, the activities of CYP in hepatic S-9 fractions were investigated. Unlike the selective inhibitory effect of mollugin on CYP1A2-catalyzed phenacetin O-deethylation in vitro, mollugin only significantly inhibited the activity of CYP2E1-catalyzed chlorzoxazone 6-hydroxylase in vivo. The activities of other CYPs were only slightly altered by mollugin. The results of this study suggest that mollugin might cause herb-drug interactions via the selective inhibition of CYP2E1 in vivo.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.6
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• pp.1201-1206
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• 2002

In oriental medicine, human being is classified into four groups according to their body constitution status (;tae-yang, tae-eum, so-yang, and so-eum persons) considering the differences in function of internal organs and characteristics. Four body constitution, called 'sa-sang' has been recognized as an important factor for diagnosing the patients before madical teratment. Yet, the criteria to divide body constitutions or its scientific principle are not clearly defined. As an initial effort to elucidate biological priciples underlying four body constitution groups, we studied genetic variations among three constitution groups (tae-eum, so-yang, and so-eum persons). Noting distinct responses to ingested food and administered drugs among three groups, SNPs and haplotype experiments were performed in 2D6, 2C9, and 1A2 DNA regions of the cytochrome P450 gene. Significant variability in SNPs types was found in 2D6 region. Moreover, haplotyping in 2D6 region showed relatively high occurrences of haplotype 3 and 5 in so-eum person, haplotype 6 in tae-eum person, and hyplotype 1 in so-yang person. These results indicate that individuals with different body constitutions respond differently to ingested food and drugs, which might reflect constitution-specific genetic background. The genetic approach would therefore be useful to reveal intrinsic differences among four constitution body groups in the responsiveness to various drugs and external stimulations to human body.

• Korean Journal of Acupuncture
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• v.24 no.1
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• pp.161-170
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• 2007

Objectives : In this study, we determinated protective effects of Vitis labrusca Root herbal-acupuncture solution (VLHA) against atherosclerosis and cardiovascular disease induced by oxidative damage and cytochrome P450 (CYP) induction. Methods : Antioxidant capacity of VLHA were evaluated by the ${\beta}-carotene/linoleic$ acid emulsion system and FeCl2-ascorbic acid stimulted lipid peroxidation in rat liver homogenate, respectively. Scavenging effects of VLHA on ONOO- and NO were measured by DHR 123, DAF-2 assay. Furthermore, we measured inhibitory activity of VLHA on CYP 2E1 in rat liver microsome using by Aniline assay. Results : VLHA exhibited potent inhibition rate(74%) on FeCl2-ascorbic acid induced lipid peroxidation, and revealed a strong scavenging effects on ONOO- and NO. In addition, VLHA showed inhibitory effect on CYP 2E1. Conclusions : The present study concludes that our results suggest that VLHA could be used as a good source in the prevention of atherosclerosis and alcoholic liver injury.