• 약학회지
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• 제41권3호
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• pp.381-388
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• 1997

Metabolism of DWP401, recombinant juman epidermal growth factor, was examined in vivo and in vitro in rats. When $^{125}I$-labeled DWP401 was administered at a dose of 50 ${\mu}g$/kg by i.v. injection. $^{125}I$-labeled DWP401 was rapidly degraded within 30 minytes above 93%. Thin layer chromatography analysis of urine collected for 24 hr after i.v. administration of $^{125}I$-labeled DWP401 showed ohly one spot on a X-ray film which was considered as diiodo-tyrosine. This result suggests tha $^{125}I$-labeled DWP401 was completely digested into free amino acids without any specific intermediate polypeptides. About 42.1% of the administered iodine was recovered in 24 hr. For in vitro degradation study, $^{125}I$-labeled DWP401 was added to plama and tissue homogenates of rats and incubated at $37^{\circ}C$. Almost 98% of the added radioactivity recovered from the protein fraction of the liver, kidey, small intestine, stomach and spleen decreased rapidly. For examplem the recovery rates of $^{125}I$-labeled DWP401 were 58.6, 63.2, 39.9, 52.9 and 66.8% after 4hrs of incubation in respective organ homogenates.

• Journal of Microbiology and Biotechnology
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• 제8권4호
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• pp.325-332
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• 1998

In vitro phosphorylation experiments with a cell extract of Streptomyces coelicolor A3(2) M130 in the presence of ${\gamma}-[^32P]$]ATP revealed the presence of multiple phosphorylated proteins, including the AfsR/AfsK kinases which control the biosynthesis of A-factor, actinorhodin, and undecylprodigiosin. Phosphorylation of AfsR by a cell extract as an AfsK source was significantly inhibited by Ser/Thr protein kinase inhibitors, staurosporine and K-252a, at concentrations giving 50% inhibition ($IC_50$) of $1{\mu}M\;and\;0.1{\mu}M$, respectively. Further in vitro experiments with the cell extracts showed that phosphorylation of multiple proteins was inhibited by various protein kinase inhibitors with different inhibitory profiles. Manganese and calcium ions in the reaction mixture also modulate phosphorylation of multiple proteins. Manganese at 10 mM greatly enhanced the phosphorylation and partially circumvented the inhibition caused by staurosporine and K-252a. A calcium-activated protein kinase(s) was little affected by these inhibitors. Herbimycin and radicicol, which are known as tyrosine kinase inhibitors, did not show any significant inhibition of AfsR phosphorylation. Consistent with the in vitro effect of the kinase inhibitors, they inhibited aerial mycelium formation and pigmented antibiotic production on solid media. On the contrary, when assayed in liquid culture, the amount of actinorhodin produced was increased by staurosporine and K-252a and greatly decreased by manganese. All of these data clearly show that the genus Streptomyces possesses several protein kinases of eukaryotic types which are involved in the regulatory network for morphogenesis and secondary metabolism.

• Mass Spectrometry Letters
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• 제9권2호
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• pp.61-65
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• 2018

KPLA-012, a benzopyranyl 1,2,3-triazole compound, is considered a potent $HIF-1{\alpha}$ inhibitor based on the chemical library screening, and is known to exhibit anti-angiogenetic and anti-tumor progressive effects. The aim of this study was to investigate the pharmacokinetic properties of KPLA-012 in ICR mice and to investigate in vitro characteristics including the intestinal absorption, distribution, metabolism, and excretion of KPLA-012. The oral bioavailability of KPLA-012 was 33.3% in mice. The pharmacokinetics of KPLA-012 changed in a metabolism-dependent manner, which was evident by the low recovery of parent KPLA-012 from urine and feces and metabolic instability in the liver microsomes. However, KPLA-012 exhibited moderate permeability in Caco-2 cells ($3.1{\times}10^{-6}cm/s$) and the metabolic stability increased in humans compared to that in mice (% remaining after 1 h; 47.4% in humans vs 14.8% in mice). Overall, the results suggest that KPLA-012 might have more effective pharmacokinetic properties in humans than in mice although further studies on its metabolism are necessary.

• Journal of Microbiology and Biotechnology
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• 제34권2호
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• pp.387-398
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• 2024

Euphorbia humifusa Willd (Euphorbiaceae) is a functional raw material with various pharmacological activities. This study aimed to validate the inhibitory effect of Euphorbia humifusa extract (EHE) on adipocyte differentiation in vitro and in a high-fat-diet (HFD)-induced mouse model to evaluate the E.a humifusa as a novel anti-obesity and lipid metabolism enhancer agent. EHE effects on obesity and lipid metabolism were assessed in HFD-induced obese mice after 4-week treatments. Results were compared among four treatment groups (n = 7/group): low fat diet (LFD), high fat diet (HFD), and HFD-induced obese mice treated with either 100 or 200 mg/kg/day EHE (EHE100 and EHE200, respectively). EHE (50 to 200 ㎍/ml) and quercetin (50 ㎍/ml) significantly reduced 3T3-L1 preadipocyte differentiation (p < 0.001), in a concentration-dependent manner. EHE affected lipid metabolism, as evidenced by changes in serum lipid components. The HFD-EHE100 and HFD-EHE200 groups exhibited significantly (p < 0.05) reduced triglycerides (TG, 97.50 ± 6.56 and 82.50 ± 13.20 mg/dL, respectively) and low-density lipoprotein-cholesterol (LDL-c: 40.25 ± 4.99 and 41.25 ± 6.36 mg/dL, respectively) compared to the HFD group (TG: 129.25 ± 19.81 mg/dL; LDL-c: 51.75 ± 11.59 mg/dL). Haematoxylin and Eosin (H&E) and Oil red O staining showed that EHE markedly reduced lipid accumulation and inhibited lipogenesis in the liver. Interestingly, EHE significantly (p < 0.01) reduced the expression of adipogenic transcription factors in liver tissue. Our results indicated that EHE has the potential to be a therapeutic agent for addressing obesity and lipid metabolism.

• BMB Reports
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• 제45권10호
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• pp.565-570
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• 2012

We recently reported that a water extract of laurel or turmeric, 1,8-cineole enriched fractions, showed hypolipidemic activity in the zebrafish model. Therefore, the present study investigated the cineole's anti-oxidant and anti-inflammatory activities in lipoprotein metabolism in vitro and in vivo. Cineole had inhibitory effects on cupric ion-mediated oxidation of lipoproteins in general, while simultaneously enhancing ferric ion removal ability in high-density lipoprotein (HDL). Hypercholesterolemia was induced in zebrafish using cholesterol-feeding treatment, 4% cholesterol, for 3 weeks. After feeding with or without the addition of cineole, the results revealed that cineole possessed lipid-lowering and anti-inflammatory activities in hypercholesterolemic zebrafish. In addition, serum amyloid A and interleukin-6 levels were lowered and lipid accumulation was decreased in the liver. Conclusively, 1,8-cineole was found to have anti-oxidant activities in lipoprotein metabolism both in vitro and in vivo with simultaneous reduction of lipid accumulation in the liver of zebrafish.

• Archives of Pharmacal Research
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• 제28권8호
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• pp.977-982
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• 2005

The aim of this study was to compare two formulations of film-coated pellets containing c1arithromycin after single oral dose study in healthy male volunteers. Two formulations with different coating polymers were prepared: formulation-1 (F-1) was prepared by incorporating three kinds of pH-dependent gradient-release coated pellets into capsules and formulation-2 (F-2) was prepared by coated with an insoluble semiosmotic film. Release profiles of filmcoated pellets were evaluated using paddle method under different conditions. Pharmacokinetic profiles of these formulations were obtained in three healthy male volunteers and compared to commercially available immediate release (IR) tablets. The relative bioavailability based on the $AUC_{0-24h}$ was found to be $96.2\%\;and\;58.7\%$ for F-1 and F-2 compared with IR, and the $T_{max}$ was delayed.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.286.2-287
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• 2003

The purpose of this paper was to identify the metabolic pathway of a new neuroprotective agent, KR-31543 for ischemia-reperfusion damage in human liver microsomes and characterize cytochrome P450 (CYP) enzymes involved in the in vitro metabolism of KR-31543 generates two metabolites in human liver microsomes : M1, N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amine and M2, hydroxy-KR-31543. (omitted)

• Mass Spectrometry Letters
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• 제2권1호
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• pp.20-23
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• 2011

The purpose of this study is to investigate the in vitro metabolism of hesperetin, a bioflavonoid. Hesperetin was incubated with rat liver microsomes in the presence of NADPH and UDP-glucuronic acid for 30 min. The reaction mixture was analyzed by liquid chromatography-ion trap mass spectrometer and the chemical structures of hesperetin metabolites were characterzed based on their MS/MS spectra. As a result, a total of five metabolites were detected in rat liver microsomes. The metabolites were identified as a de-methylated metabolite (eriodictyol), two hesperetin glucuronides, and two eriodictyol glucuronides.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.253.1-253.1
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• 2002

DA-8159 is a new PDEV inhibitor, synthesized by Dong-A Pharm, as an oral agent to treat male erectile dysfunction. DA-8159 and sildenafil are mainly metabolized by cytochrome P450 enzyme CYP 3A4. In this study. we compared the metabolism of DA-8159 with sildenafil in vitro and in vivo. First, we quantified the remaining gatio of original compound, DA-8159 and sidenafil., after we incubated drugs for 30 minutes with human liver microsome cytochrome P 450 3A4. (omitted)

• 생명과학회지
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• 제9권4호
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• pp.382-388
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• 1999

The effects of citrus flavonoids, hesperidin and naringin, on the lipid metabolism were investigated in cultured human hepatocyte HePG2 cells. HepG2 cells were cultured for 6 h and 24 h to the control medium or the media containing hespridin and narigin, which concentrations were 0.5 and 5.0 mg/$m\ell$. There were no significant effects on cell proliferation and cellular protein content, except for increased in these parameters by adding both citrus flavonoids (0.5 mg/$m\ell$). The cellular content of triacylglycerol after 6 h incubation with 0.5 mg/$m\ell$ hesperidin and naringin was markedly increased, and after 24 h incubation that was decreased in both citrus flavonoids supplementation. The supplementation of 5.0 mg/$m\ell$ hesperidin caused a marked decrease in the cellular cholesterol content following 6 h incubation, and that was also reduced markdly, in a dose-dependent manner, during incubation for 24 h. However, there was no significant difference in the cellular cholesterol content in medium supplemented with naringin. The effect of hesperidin and naringin on acyl-CoA: cholesterol acyltransferase (ACAT) activity was studied in vivo and in vitro. The data confirmed that hesperidin inhibit ACAT activity in vivo and in vitro, whereas naringin had no such effect on ACAT activity in vivo but not in vitro. The present study suggests that hesperidin reduces the cellular triacyglycerol and cholesterol contents in human hepatocyte HepG2 cells.