• 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 Photoscience
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• v.9 no.2
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• pp.94-97
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• 2002

Light is one of the most important environmental factors that influence plant growth and development. It does not function independently but exerts its role through coordinated interactions with intrinsic developmental programs, such as hormonal regulation. One typical example is hypocotyl growth in which light signals are modulated through growth hormones. However, the underlying molecular mechanisms are largely unknown. We demonstrated that brassinosteroids play an important role in the light signal transduction in etiolated hypocotyl growth. A light-responsive Ras-like G-protein, Pra2 from pea, physically and functionally interacts with a cytochrome P450 that specifically catalyzes C-2 hydroxylation in brassinosteroid biosynthesis. The cytochrome P450 expression, along with Pra2, is induced in the dark and predominantly localized in the rapidly elongating zone of etiolated pea epicotyls. Transgenic plants with a reduced level of Pra2 exhibit a dark-specific dwarfism, which is completely rescued by brassinosteroid application. On the contrary, overexpression of the cytochrome P450 results in enhanced hypocotyl growth even in the light, which phenocopies the etiolated hypocotyl growth. It is therefore envisioned that Pra2 is a molecular switch that mediates the crosstalk between light and brassinosteroids in the etiolation process.

• 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.

• 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.

• Toxicological Research
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• v.32 no.3
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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.

• Biomolecules & Therapeutics
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• v.22 no.2
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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.

• Analytical Science and Technology
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• v.5 no.1
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• pp.83-90
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• 1992

The $^{14}C$-warfarin used as rodenticids was identified from various organs of sprague dawley with scintillation counter. And the cytochrome p-450 which was induced by coumarin derivatives was identified with electrophoresis. The distributions of $^{14}C$-warfarin after $14.8{\mu}Ci/kg$ oral application at each organ was as follows; urine-7.5%, blood-0.44%, feces-0.9%, liver-0.66%, lung-0.86%, kidney-0.8%, heart-0.43% and spreen-0.33% after 24hrs. The cytochrome p-450 was purified by Octyl Sepharose CL-4B hydrophobic chromatography and isozymes were 50.8 Kd in control group, 53.3 Kd and 55.2 Kd in coumarin pretreated group and 50.8 Kd, 54.6 Kd and 57.7 Kd in warfarin pretreated group.

• Journal of Ginseng Research
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• v.36 no.2
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• pp.198-204
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• 2012

An light-emitting diode (LED)-based light source was used as a monochromatic light source to determine the responses of raw ginseng roots (Panax ginseng Meyer) to specific emission spectra with respect to the production of ginsenosides. The ginsenoside content in the ginseng roots changed in response to the LED light treatments at $25^{\circ}C$ relative to the levels in the control roots that were treated in the dark or at $4^{\circ}C$ for 7 d. Ginseng roots were exposed to LEDs with four different peak emission wavelengths, 380, 450, 470, and 660 nm, in closed compartments. Compared with the control $4^{\circ}C$-treated roots, roots that were treated with 450 and 470 nm light showed a significantly increased production of ginsenosides (p<0.05), with increases of 64.9% and 74.1%, respectively. The contents of the ginsenosides $Rb_2$, Rc, and $Rg_1$ were significantly higher (p<0.05) in the 450 and 470 nm-treated root samples. The ratio of protopanaxadiol ginsenosides ($Rb_1$, $Rb_2$, Rc, and Rd) to protopanaxatriol ginsenosides ($Rb_1$, $Rb_2$, Re, and Rf) was significantly higher (p<0.05) in the 450 and 470 nm-treated root samples than in the control $4^{\circ}C$-treated roots. This is the first report that demonstrates the increase and conversion of ginsenosides in raw ginseng roots in response to exposure to LED light.

• 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.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.404.1-404.1
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• 2002

A LC/MS/MS method for the simultaneous determination of the activities of seven major human drug-metabolizing cytochrome P450s (CYP3A4. CYP2D6. CYP2C9. CYP1A2, CYP2C19, CYP2A6. and CYP2C8) was developed. This method used an in vitro cocktail of specific substrates (midazolam. bufuralol. diclofenac, ethoxyresorufin. S-mephenYlOin. coumarin. and paclitaxel) and LC/MS/MS. The assay incubation time is 20 min and the analysis time is 8 min/sample. (omitted)