• Nutrition Research and Practice
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• v.1 no.3
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• pp.175-179
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• 2007

The present study was performed to elucidate the hypocholesterolemic action of chitosan on the diet-induced hypercholesterolemia in rats. Male Sprague-Dawley rats (n=24) were fed with chitosan-free diet (Control), diets containing 2% or 5% chitosan for 4 weeks. Hypercholesterolemia was induced by adding 1% cholesterol and 0.5% cholic acid to all diets. Body weight gain and food intake of rats did not differ among the groups. The chitosan treated groups showed significant improvement in the plasma concentration of total cholesterol and LDL-cholesterol compared to the control group (p<0.05). Also, the chitosan treated groups decreased the liver concentration of total lipid and total cholesterol compared to the control group (p<0.05). The activity of hepatic cholesterol $7{\alpha}-hydroxylase$ (CYP7A1), the rate-limiting enzyme in the conversion of cholesterol to bile acids, was increased by 123% and 165% for the 2% or 5% chitosan diets, respectively. These findings suggest that enhancement of hepatic CYP7A1 activity may be a mechanism, which can partially account for the hypocholesterolemic effect of dietary chitosan in cholesterol metabolism.

• Mass Spectrometry Letters
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• v.8 no.4
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• pp.98-104
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• 2017

Ginseng (Panax ginseng Meyer) is a well-known health functional food used as a traditional herbal drug in Asian countries owing to its diverse pharmacological effects. Herb-drug interactions may cause unexpected side effects of co-administered drugs by the alteration of pharmacokinetics through effects on cytochrome P450 activity. In this study, we investigated the herb-drug interactions between Korean red ginseng extract (KRG) and five CYP-specific probes in mice. The pharmacokinetics of KRG extract induced-drug interactions were studied by cassette dosing of five CYP substrates for CYP1A, 2B, 2C, 2D, and 3A and the LC-MS/MS analysis of the blood concentration of metabolites of each of the five probes. The linearity, precision, and accuracy of the quantification method of the five metabolites were successfully confirmed. The plasma concentrations of five metabolites after co-administration of different doses of the KRG extract (0, 0.5, 1, and 2 g/kg) were quantified by LC-MS/MS and dose-dependent pharmacokinetic parameters were determined. The pharmacokinetic parameters of the five metabolites were not significantly altered by the dose of the KRG extract. In conclusion, the single co-administration of KRG extract up to 2 g/kg in vivo did not cause any significant herb-drug interactions linked to the modulation of CYP activity.

• Mass Spectrometry Letters
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• v.7 no.3
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• pp.69-73
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• 2016

High-resolution quadrupole-Orbitrap mass spectrometry (HRMS), with high-resolution (> 10,000 at full-width at half-maximum) and accurate mass (< 5 ppm deviation) capabilities, plays an important role in the structural elucidation of drug metabolites in the pharmaceutical industry. ML106, a derivative of imidazobenzimidazole, decreased melanin content and tyrosinase activity in a dose-dependent manner. Here, we investigated the phase 1 metabolic pathway of ML106 using HRMS in human liver microsomes (HLMs) and recombinant cDNA-expressed cytochrome P450 (CYP). After the incubation of ML106 with pooled HLMs and recombinant cDNA-expressed CYP in the presence of NADPH, five phase 1 metabolites, including three mono-hydroxylated metabolites (M1-3) and two di-hydroxylated metabolites (M4 and M5), were investigated. The metabolite structures were postulated by the elucidation of protonated mass spectra using HRMS. The CYP isoforms related to the hydroxylation of ML106 were studied after incubation with recombinant cDNA-expressed CYP. Here, we identified the phase 1 metabolic pathway of ML106 induced by CYP in HLMs.

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.269.3-269.3
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• 2001

• Advances in Traditional Medicine
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• v.8 no.3
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• pp.207-214
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• 2008

In recent years, the combined use of Herbal medicines and Western drugs has been increasing. Though certain problems may occur when both types of medicines are taken together, they havenot been adequately analyzed. It was reported that anticoagulation was enhanced in addition tobleeding when patients took long-term warfarin therapy in combination with Salvia miltiorrhiza(danshen), and laxative herbs accelerate intestinal transit and interfere with the absorption. Herbal constituents, curcumin, ginsenosides, piperine, catechins and silymarin were found to beinhibitors of P-glycoprotein. St John's wort induces the intestinal expression of P-glycoprotein. Anthraquinone, quercetin and coumarins were found to be a potent inhibitor of P-450. Glycyrrhizin or liquorice extracts, Garlic and St John's wort are a potent inducer of CYP3A4. This review provides a critical overview of interactions between herbal medicines and other drugs. Hence, it is necessary to study the pharmacodynamic and pharmacokinetic interactions of many herbal medicines between western drugs.

• Journal of Food Hygiene and Safety
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• v.15 no.3
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• pp.226-234
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• 2000

Protective effect of Corydalis ternata against the carbon tetrachloride-induced toxicity was investigated. Carbon tetrachloride($CCl_4$) induces hepatotoxicity due to the reactive free radical(CCl$_3$ . ) generated by cytochrome P-450 enzyme. We examined effects of hexane, chloroform, butanol and water fractions prepared from the Corydalis ternata methanol extract. Rats were treated with those for 3 days, and liver microsomes and cytosols were prepared at 24 hour after last treatment. Hepatoprotective activity of the water fraction was higher than that of other fractions. To examine mechanism of the hepatoprotective effect of Corydalis ternuta, we measured contents of malondialdehyde(MDA), cytochrome P46O(CYP), glutathione, calcium as well as the activities of NADPH-CYP reductase, glutathione S-transferase(GST), superoxide dismutase(SOD), glutathione peroxidase(GPX) and catalase. The fraction inhibited production of MDA, content of CYP and calcium in liver of water fractions - treated rats as compared with those of CCl4-treated rats. The GST activity was increased. We speculate that the O2 radical scavenging activities of the water fraction might play a key role in the mechanism opposing the progression of $CCl_4$-induced hepatotoxicity, but the activities of SOD, GPX, CAT were decreased. These results suggest that the mechanism might be mainly due to the decrease of CYP contents, act as calcium channel blocker and increase of GST activity rather than $O_2$ radical scavenging activities.

• Biomolecules & Therapeutics
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• v.25 no.3
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• pp.288-295
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• 2017

The incidence of polypharmacy-which can result in drug-drug interactions-has increased in recent years. Drug-metabolizing enzymes and drug transporters are important polypharmacy modulators. In this study, the effects of bosentan and rifampin on the expression and activities of organic anion-transporting peptide (OATP) and cytochrome P450 (CYP450) 2C9 and CYP3A4 were investigated in vitro. HEK293 cells and primary human hepatocytes overexpressing the target genes were treated with bosentan and various concentrations of rifampin, which decreased the uptake activities of OATP transporters in a dose-dependent manner. In primary human hepatocytes, CYP2C9 and CYP3A4 gene expression and activities decreased upon treatment with $20{\mu}M$ $bosentan+200{\mu}M$ rifampin. Rifampin also reduced gene expression of OATP1B1, OATP1B3, and OATP2B1 transporter, and inhibited bosentan influx in human hepatocytes at increasing concentrations. These results confirm rifampin- and bosentan-induced interactions between OATP transporters and CYP450.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.11a
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• pp.118-118
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• 2004

• Journal of Society of Preventive Korean Medicine
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• v.12 no.2
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• pp.37-49
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• 2008

In this study, we experimented the influence of three herbal medicines, which are Saussurea lappa Clarke, Poncirus trifoliata Rafin, Citrus aurantium Linne, which are called 'Yigiyak(理氣藥)' on drug metabolizing enzyme cytochrome P450 3A4 in Human Liver Microsome. Above all, the reason for this study is that herbal medicines can be assumed that herbs might have interactions with drugs, other herbs, alcohol and chemicals whether those are much better synergy effects than expected effects when the medicine was treated alone or not. As a result, we showed that all of five traditional herbal medicines had no CYP 3A4 inhibition effect on 10, 20, 30, 40, $50{\mu}g/m{\ell}$ doses in Human Liver Microsome even Saussurea lappa Clarke showed a little inhibition as about 93% and 79% inhibition rate of control. However, this result are mostly not enough to prove that SLC has a CYP 3A4 inhibition effect. Moreover, it is not that those rates showed that those herbal medicines have CYP 3A4 induction effect. In conclusion, the result could support that those herbal medicines are more safe than chemical drugs even if this is the basic step to prove that result. Therefore, more specific studies to support this result, which are Kinetic study, cell and animal study then finally until clinical research, are required.

• Biomolecules & Therapeutics
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• v.17 no.2
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• pp.205-210
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• 2009

The present study investigated the effects of hydrocortisone on the pharmacokinetics of loratadine in rats after intravenous and oral administration. A single dose of loratadine was administered either orally (4 mg/kg) or intravenously (1 mg/kg) with or without oral hydrocortisone (0.3 or 1.0 mg/kg). Compared to the control group (without hydrocortisone), after oral administration of loratadine, the area under the plasma concentration-time curve (AUC) was significantly increased by 30.2-81.7% in the presence of hydrocortisone (p<0.05). The peak plasma concentration ($C_{max}$) was significantly increased by 68.4% in the presence of 1.0 mg/kg hydrocortisone after oral administration of loratadine (p<0.05). Hydrocortisone (1.0 mg/kg) significantly increased the terminal plasma half-life ($t_{1/2}$) of loratadine by 20.8% (p<0.05). Consequently, the relative bioavailability of loratadine was increased by 1.30- to 1.82-fold. In contrast, oral hydrocortisone had no effects on any pharmacokinetic parameters of loratadine given intravenously. This suggests that hydrocortisone may improve the oral bioavailability of loratadine by reducing first-pass metabolism of loratadine, most likely mediated by P-gp and/or CYP3A4 in the intestine and/or liver. In conclusion, hydrocortisone significantly enhanced the bioavailability of orally administered loratadine in rats, which may have been due to inhibition of both CYP 3A4-mediated metabolism and P-gp in the intestine and/or liver by the presence of hydrocortisone.