• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Dietary and Medicinal Antimutgens and Anticarcinogens
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• pp.198-198
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• 2001

No report has been addressed to the CYP isoforms catalyzing chlorpropamide, a structural analogue of tolbutamide. To evaluate enzyme(s) mediating formation of 2-hydroxycWorpropamide, a major metabolite and identified by LC/Mass and NMR, incubation studies using human liver microsomes and cDNA expressed CYP were performed on the presence or absence of selective inhibitors of each CYP isoform. (omitted)

• Archives of Pharmacal Research
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• 제11권4호
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• pp.292-300
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• 1988

Metabolism of tranylcypromine (TCP) in rat liver microsomes was studied in vitro using fortified microsomal preparations. As well as unlabeled TCP, two deuterium labeled analogs, TCP-phenyl-$d_{5}$ and TCP-cyclopropyl-$d_{2}$ were used and GC/MS employed which was then metabolized to cinnamaldehyde and hydrocinnamyl alcohol. Schiff bases of TCP with hydrocinnamaldehyde and acetaldehyde were detected and possibility of the metabolic formation of N-ethylidene TCP was proposed. In addition, acetophenone (benzoylacetic acid), benzaldehyde, benzoic acid, and benzyl alcohol were detected as the metabolites. Chemical decomposition studies suggested that parts of the oxidized products might be derived by air oxidation processes. A potential metabolite assumed to be N-ethylidene-1, 2-dihydroxy-3-phenylpropanamine oxide was also detected.

• Journal of Ginseng Research
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• 제42권4호
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• pp.512-523
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• 2018

Background: 20(S)-Protopanaxadiol (20S-PPD) is a fully deglycosylated ginsenoside metabolite and has potent dermal antiaging activity. However, because of its low aqueous solubility and large molecular size, a suitable formulation strategy is required to improve its solubility and skin permeability, thereby enhancing its skin deposition. Thus, we optimized microemulsion (ME)-based hydrogel (MEH) formulations for the topical delivery of 20S-PPD. Methods: MEs and MEHs were formulated and evaluated for their particle size distribution, morphology, drug loading capacity, and stability. Then, the deposition profiles of the selected 20S-PPD-loaded MEH formulation were studied using a hairless mouse skin model and Strat-M membrane as an artificial skin model. Results: A Carbopol-based MEH system of 20S-PPD was successfully prepared with a mean droplet size of 110 nm and narrow size distribution. The formulation was stable for 56 d, and its viscosity was high enough for its topical application. It significantly enhanced the in vitro and in vivo skin deposition of 20S-PPD with no influence on its systemic absorption in hairless mice. Notably, it was found that the Strat-M membrane provided skin deposition data well correlated to those obtained from the in vitro and in vivo mouse skin studies on 20S-PPD (correlation coefficient $r^2=0.929-0.947$). Conclusion: The MEH formulation developed in this study could serve as an effective topical delivery system for poorly soluble ginsenosides and their deglycosylated metabolites, including 20S-PPD.

• Journal of Plant Biotechnology
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• 제43권1호
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• pp.104-109
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• 2016

Rosa rugosa is a medicinal, ornamental, and edible plant native to Eastern Asian countries, including Korea, Japan, and China. The aim of this study was to establish a system for biomass production and secondary metabolite accumulation during in vitro culture and acclimatization of Rosa rugosa. The highest rate of multiple shoot proliferation was achieved with $8.8{\mu}M$ benzyladenine (BA) (83.3%). However, the number of shoots (14.4 per explant) at $4.4{\mu}M$ BA was higher than that at $8.8{\mu}M$ BA. Compared to BA, a combination of thidiazuron (TDZ) and indole butyric acid (IBA) exhibited significantly lower shoot induction, with only 50.0~79.2% and 4.2~16.7% relative shoot formation, respectively. During acclimatization, shoots were sampled every week and their total phenolic contents were analyzed. Among various growth factors, fresh weight showed the most dramatic increase from the 3rd week (88.0 mg/plant) to 4th week (132.7 mg/plant). Total phenolics and flavonoids contents were the highest at $1^{st}$ week of acclimatization. Depending on developmental stages, total phenolics and flavonoids contents were higher in 1-yr-old shoots grown ex vitro than in those of older field-grown or in vitro-grown plants. Amongst different ages of field grown plants, 6-year-old plants, the oldest in this study, showed the lowest content in total phenolics.

• Mycobiology
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• 제39권3호
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• pp.174-181
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• 2011

The purpose of the present study was to investigate the influence of cultural and environmental parameters affecting the growth and bioactive metabolite production of the rare strain VUK-10 of actinomycete Pseudonocardia, which exhibits a broad spectrum of in vitro antimicrobial activity against bacteria and fungi. Production of bioactive metabolites by the strain was high the in modified yeast extract-malt extract-dextrose (ISP-2) broth, as compared to other tested media. Glucose (1%) and tryptone (0.25%) were found to be the most suitable carbon and nitrogen sources, respectively, for optimum production of growth and bioactive metabolites. Maximum production of bioactive metabolites was found in the culture medium with initial pH 7 incubated with the strain for four days at $30^{\circ}C$, under shaking conditions. This is the first report on the optimization of bioactive metabolites by Pseudonocardia sp. VUK-10.

• Biomolecules & Therapeutics
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• 제16권3호
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• pp.190-196
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• 2008

Deoxypodophyllotoxin (DPT) is a medicinal herb product isolated from Anthriscus sylvestris. DPT possesses beneficial activities in regulating immediate-type allergic reaction and anti-inflammatory activity through the dual inhibition of cyclooxygenase-2 and 5-lipoxygenase. In the present study, the metabolism of DPT was further characterized in rat liver microsomes isolated from male Sprague Dawley rats. The metabolism of DPT was NADPH-dependent. In addition, when liver microsomes were incubated with SKF-525A, a well-known CYP inhibitor, in the presence of $\beta$-NADPH, the metabolism of DPT was significantly inhibited. Using enriched rat liver microsomes, the anticipated isoforms of cytochrome P450s (CYPs) in the metabolism of DPT were partially characterized. Phenobarbital-induced microsomes increased in the formation of metabolite M1. The metabolite M3 was only produced in the enriched microsomes isolated from dexamethasone-treated rats. The results indicated that the metabolism of DPT would be CYP-dependent and that CYP2B and CYP3A might be important in the metabolism of DPT in rats.

• Bulletin of the Korean Chemical Society
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• 제35권11호
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• pp.3188-3194
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• 2014

Compound K (CK) was formulated as polymeric micelles (PM) using Pluronic$^{(R)}$ F-127 to enhance the oral absorption of CK, an intestinal bacterial metabolite of ginseng protopanaxadiol saponin. The physicochemical properties of Ck-loaded PM were characterized and an in vitro transport study using the Caco-2 cell system as well as an in vivo pharmacokinetic study using SD rats was carried out. The hydrodynamic mean particle size of CK-loaded PM (CK-PM) was $254{\pm}23.45nm$ after rehydration and the drug loading efficiency was ca. 99.9%. The FT-IR spectroscopy, X-ray diffraction, differential scanning calorimetry and scanning electron microscopy data supported the presence of a new solid phase in the PM. The $P_{app}$ value of in vitro Caco-2 cell permeation of CK-PM and the oral absorption of CK was enhanced about 1.2-fold and 2.6-fold compared to CK suspension, respectively, showing that the present PM formulation enabled an enhancement of oral CK absorption.

• Journal of Plant Biotechnology
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• 제50권
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• pp.97-107
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• 2023

Malaria remains to be one of the most severe global public health concerns. Traditionally, Aspilia Africana and Warburgia ugandensis have been used to treat malaria in several African countries for millennia. In the current study, A. africana calli (AaC), A. africana in vitro roots (AaIR), A. africana wild leaf (AaWL), and W. ugandensis stem bark (WuSB) were dried and pulverized. Fourier transform near-infrared spectroscopy was used to analyze the powdered samples, while 80% ethanolic extracts of each sample were assayed for antiplasmodial activity (against Plasmodium falciparum strains DD2 (chloroquine-resistant) and 3D7 (chloroquine-sensitive)) and cytotoxicity. WuSB showed the highest antiplasmodial activity (IC₅₀ = 1.57 ± 0.210 ㎍/ml and 8.92 ± 0.365 ㎍/ml against P. falciparum 3D7 and DD2, respectively) and selectivity indices (43.90 ± 7.914 and 7.543 ± 0.051 for P. falciparum 3D7 and DD2, respectively). The highest total polyphenolic contents (total phenolic and flavonoid contents of 367.9 ± 3.55 mg GAE/g and 203.9 ± 1.43 mg RUE/g, respectively) were recorded for WuSB and the lowest were recorded for AaC. The antiplasmodial activities of the tested plant tissues correlated positively with total polyphenolic content. The high selectivity indices of WuSB justify its traditional applications in treating malaria and present it as a good candidate for discovering new antimalarial compounds. We recommend elicitation treatment for AaIR, which showed moderate antiplasmodial activity against P. falciparum DD2, to increase its secondary metabolite production for optimal antimalarial activity.

• Natural Product Sciences
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• 제5권4호
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• pp.162-164
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• 1999

Dehydroaltenusin (1) was isolated from the chloroform extract of the culture filtrate of a Streptomyces sp. and its structure was determined from spectral data as well as by comparison with published values. In an XTT-based in vitro anti-HIV assay, dehydroaltenusin effectively inhibited the cytopathic effects of HIV infection at a concentration of $1-5\;{\mu}g/mL$.

• 한국임상약학회지
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• 제23권4호
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• pp.322-326
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• 2013

Purpose: Telmisartan, an angiotensin receptor blocker has been known to be a potent blocker of both CYP2J2 and P-glycoprotein (P-gp) in vitro. This study aims to investigate the drug-drug interactions between telmisartan and ebastine, a CYP2J2 and P-gp substrate in rats. Method: Ebastine (10 mg/kg) was orally given in the presence and absence of telmisartan (4 mg/kg, p.o.). Heparinized blood was serially taken and the plasma concentrations of ebastine and its three metabolites (hydroxyebastine, carebastine and desalkylebastine) were determined using LC-MS/MS, and their pharmacokinetic parameters were compared. Results: Peak concentrations ($C_{max}$) and AUC of ebastine were significantly (p<0.05) increased in the presence of telmisartan by 2.1 and 1.9 times, respectively. While $C_{max}$ of hydroxyebastine was significantly increased by 1.9 times, the half-life of hydroxyebasteine was decreased significantly with telmisartan (p<0.05). There was no change in the pharmacokinetic parameters of carebastine, the active metabolite of ebastine, and desalkylebastine was not detected in plasma. The systemic exposure of ebastine was significantly augmented by telmisartan, indicating that telmisartan may enhance the absorption of ebastine by blocking P-gp. Conclusion: Although telmisartan may also partially contribute to inhibit the biotransformation to hydroxyebastine, the inhibitory action seemed to be overridden by the enhancement of absorption, because the generation of hydroxyebastine was not diminished. In spite of such interactions between telmisartan and ebastine, no clinical consequence could be expected due to no significant change of the active metabolite, carebastine.