• Journal of Pharmaceutical Investigation
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• v.34 no.3
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• pp.209-214
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• 2004

A bioequivalence study of $Roxithrin^{TM}$ tablet (Kukje Pharma. Ind. Co., Ltd.) to $Rulid^{TM}$ tablet (Han Dok Pharma. Ind. Co., Ltd.) was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty four healthy male Korean volunteers received each medicine at the roxithromycin dose of 300 mg in a $2{\times}2$ crossover study. There was a one-week wash-out period between the doses. Plasma concentrations of roxithromycin were monitored by a high-performance liquid chromatography for over a period of 36 hours after drug administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 36 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters indicating that the cross-over design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for $Roxithrin^{TM}/Rulid^{TM}$ were 1.00 - 1.13 and 0.98 - 1.10, respectively. These values were within the acceptable bioequivalence intervals of 0.80 - 1.25. Thus, our study demonstrated the bioequivalence of $Roxithrin^{TM}$ and $Rulid^{TM}$ with respect to the rate and extent of absorption.

• Journal of Pharmaceutical Investigation
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• v.41 no.3
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• pp.191-196
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• 2011

In this study simple and sensitive high performance liquid chromatographic method using a commercially available column, was developed and validated for the determination of zolpidem tartrate in human plasma. The developed method with suitable validation was applied to a bioequivalence study of two different kinds of zolpidem tartrate. Two different formulations containing 10 mg of zolpidem tartate (CAS : 99294-93-6) were compared in 24 healthy male volunteers in order to compare the bioavailability and prove the bioequivalence. The study was performed in an open, single dose randomized, 2-sequence, cross-over design in 24 healthy male volunteers with a one-week washout period. Blood samples for pharmacokinetic profiling were drawn at selected times during 12 h. The mean $AUC_{0-12h}$, $C_{max}$, $T_{max}$ and $T_{1/2}$ were $676.6{\pm}223.4$ $ng{\cdot}h{\cdot}mL^{-1}$, $177.4{\pm}34.2$ $ng{\cdot}mL^{-1}$, and $0.8{\pm}0.4$ and $3.5{\pm}2.1$, respectively, for the test formulations, and $640.7{\pm}186.6$ $ng{\cdot}h{\cdot}mL^{-1}$, $193.0{\pm}64.5$ $ng{\cdot}mL^{-1}$, and $0.9{\pm}0.4$ and $2.7{\pm}0.9$, respectively, for the reference formulation. Both primary target parameters $AUC_{0-12h}$ and $C_{max}$ were log-transformed and tested parametrically by analysis of variance (ANOVA). 90% confidence intervals of $AUC_{0-12h}$ and $C_{max}$ were in the range of acceptable limits of bioequivalence (80-125%). Based on these results, the two formulations of zolpidem tartate are considered to be bioequivalent.

• Journal of Applied Biological Chemistry
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• v.59 no.4
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• pp.331-336
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• 2016

Analytical methods for methiozolin in soil, water and turfgrass were established and dissipation patterns of methiozolin in soil and turfgrass were elucidated. Analysis was done using a high performance liquid chromatography with an ultra violet detector at the wavelength of 280 nm after extraction with acetone, liquid-liquid partition with dichloromethane, and a solid phase extraction purification. Limit of determination and Limit of quantitation were 1.0, 0.5, 1.0 ng, and 0.001, 0.1, 0.01 mg/kg for water, turfgrass, and soil, respectively. Recovery rates of methiozolin from soil, water, and turfgrass were ranged 87.5~111.3, 92.8~97.4, and 78.2~98.5 %, respectively. The turfgrass and soil samples were collected at 0, 1, 4, 7, 14, 30, 45, and 60 after spray on green area in golf course. Residues of methiozlolin were not translocated to lower soil layer but detected only in turfgrasses and root area of turfgrass. Half-lives of methiozolin in turfgrass were 10.7 days and 8.8 days in soil from root area.

• Journal of Applied Biological Chemistry
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• v.59 no.4
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• pp.365-372
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• 2016

The objective of the present study was to evaluate the protective effect of red ginseng (RG) according to steaming time on 150 mM HCl/60 % ethanol induced gastric ulcer models in mice. The sample was divided into 3 groups-G (dried ginseng), RG 4 (steamed 4 h and dried ginseng), RG 6 (steamed 6 h and dried ginseng), and determined through in vitro experiments, such as 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azinobis-3-ethyl-benzothiazoline-6-sulfonic acid radical scavenging activity, HPLC analysis, total polyphenol, and flavonoid contents. In vitro experiment results were depended on steaming hours. Based on the results, we chose two samples (G, RG 6) and conducted in vivo experiments. Mice were divided into 5 groups: Nor (normal group), Con (acute gastritis mice treated with distilled water), G (gastris induced by HCl/Ethanol treated with 100 mg/kg G), RG 6 (gastris induced by HCl/ethanol treated with 100 mg/kg RG 6), and SC (gastris induced by HCl/Ethanol treated with 10 mg/kg sucralfate). In our results revealed that RG 6 suppressed elevated reactive oxygen species, and inflammatory related makers, such as cyclooxygenase-2, inducible nitric oxide synthase, tumor necrosis factor alpha, and interleukin-1 beta. In addition, gastric lesion area was improved. These results suggest that RG 6 protects the stomach by attenuating oxidative stress and inflammatory response under gastric ulcer conditions. Therefore, RG 6 should be a potential therapeutic agent for the treatment of acute gastric ulcer.

• Environmental Analysis Health and Toxicology
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• v.21 no.1 s.52
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• pp.45-56
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• 2006

This study was conducted to investigate seasonal distributions of fine particles ($PM_{2.5}$) and associated polycyclic aromatic hydrocarbons (PAHs) at three cities. $PM_{2.5}$ samples were collected on glass fiber filters at urban (Chuncheon), metropolitan (Seoul), and industrial complex sites (Ulsan) from September, 2002 to February, 2004 using the Andersen FH 95 Particulate Sampler. About five 24-hour samples were collected from each site per season. The filters were analyzed for mass and six selected PAHs concentrations. $PM_{2.5}$ concentrations were the highest either in winter or spring, which could be attributed to the increase of fossil fuel combustion in winter or the transport of yellow sand to the Korean peninsula from China in spring, respectively. Regional $PM_{2.5}$ concentrations were higher in the order of Seoul>Chuncheon>Ulsan without statistical difference among cities. The filters were extracted using dichloromethane in an ultrasonicator and analyzed for six PAHs (anthracene, fluoranthene, pyrene, benzo[a]anthracene, chrysene, and benzo[a]pyrene) with HPLC. Total PAHs concentrations were statistically different among seasons in each site, and the highest concentrations were observed in winter at each sampling site. For total samples collected, the median total PAHs concentrations in Chuncheon ($4.6ng/m^3$) and Seoul ($4.4ng/m^3$) were approximately two times higher than that in Ulsan ($2.1ng/m^3$). Chrysene was a component found in the highest proportion among total PAHs at each site. Carcinogenic risks calculated based on the BaP toxic equivalency factors (TEFs) over the whole sampling period were higher in the order of Chuncheon>Seoul>Ulsan. This study suggests that the atmosphere of Chuncheon is contaminated with particulate matter and PAHs at the levels equivalent to those of Seoul and that an appropriate measure needs to be taken to mitigate human health risks from inhalation exposure to airborne fine particles.

• Proceedings of the Korean Society of Food Science and Nutrition Conference
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• 2001.12a
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• pp.95-109
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• 2001

The traditional (European) Mediterranean diet is characterized by an abundance of plant foods such as bread, pasta, vegetables, salad, legumes, fruit, nuts; olive oil as the principal source of fat; low to moderate amounts offish, poultry, dairy products and eggs; only small amounts of red meat; low to moderate amounts of wine, normally consumed with meals. This diet is low in saturated fatty acids, rich in carbohydrate and fibre, and has a high content of monounsaturated fatty acids (MUFA). These are primarily derived from olive oil. Despite a wealth of general knowledge concerning the major classes of compounds present in olives and olive oil, detailed knowledge of the phenolic antioxidant content has been lacking. Therefore the aim of the study was to evaluate the phenolic antioxidant content in a range of olive and seed oils. While seed oils were devoid, on average, the olive oils contained $196{\pm}19mg/kg$ total phenolics as judged by HPLC analysis, but the value for extravirgin ($232{\pm}15 mg/kg$) was significantly higher than that of refined virgin olive oil ($62{\pm}12mg/kg$; P<0.0001). Appreciable quantities of simple phenols (hydroxytyrosol and tyrosol) were detected in olive oils, with significant differences between extravirgin ($41.87{\pm}6.17$) and refined virgin olive oils ($4.72{\pm}2.15$; P<0.01). The major linked phenols were secoiridoids and lignans. Although extravirgin contained higher concentrations of secoiridoids ($27.72{\pm}6.84$) than refined olive oils ($9.30{\pm}3.81$) this difference was not significant. On the other hand the concentration of lignans was significantly higher (P<0.001) in extravirgin ($41.53{\pm}3.93$) compared to refined virgin olive oils ($7.29{\pm}2.56$). All classes of phenolics were shown to be potent antioxidants. In future epidemiolgic studies, both the nature and source of olive oil consumed should be differentiated in ascertaining cancer risk.

• Journal of Ginseng Research
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• v.41 no.4
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• pp.572-577
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• 2017

Background: Panax ginseng Meyer is cultivated because of its medicinal effects on the immune system, blood pressure, and cancer. Major ginsenosides in fresh ginseng are converted to minor ginsenosides by structural changes such as hydrolysis and dehydration. The transformed ginsenosides are generally more bioavailable and bioactive than the primary ginsenosides. Therefore, in this study, hydrothermal processing was applied to ginseng preparation to increase the yields of the transformed ginsenosides, such as 20(S)-Rg3, Rk1, and Rg5, and enhance antioxidant activities in an effective way. Methods: Ginseng extract was hydrothermally processed using batch reactors at $100-160^{\circ}C$ with differing reaction times. Quantitative analysis of the ginsenoside yields was performed using HPLC, and the antioxidant activity was qualitatively analyzed by evaluating 2,2'-azino-bis radical cation scavenging, 2,2-diphenyl-1-picrylhydrazyl radical scavenging, and phenolic antioxidants. Red ginseng and sun ginseng were prepared by conventional steaming as the control group. Results: Unlike steaming, the hydrothermal process was performed under homogeneous conditions. Chemical reaction, heat transfer, and mass transfer are generally more efficient in homogeneous reactions. Therefore, maximum yields for the hydrothermal process were 2.5-25 times higher than those for steaming, and the antioxidant activities showed 1.6-4-fold increases for the hydrothermal process. Moreover, the reaction time was decreased from 3 h to 15-35 min using hydrothermal processing. Conclusion: Therefore, hydrothermal processing offers significant improvements over the conventional steaming process. In particular, at temperatures over $140^{\circ}C$, high yields of the transformed ginsenosides and increased antioxidant activities were obtained in tens of minutes.

• Journal of Ginseng Research
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• v.42 no.4
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• pp.562-570
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• 2018

Background: Lung cancer is the leading cause of cancer-related death worldwide. In this study, we used a bioactivity-guided isolation technique to identify constituents of Korean Red Ginseng (KRG) with antiproliferative activity against human lung adenocarcinoma cells. Methods: Bioactivity-guided fractionation and preparative/semipreparative HPLC purification were used with LC/MS analysis to separate the bioactive constituents. Cell viability and apoptosis in human lung cancer cell lines (A549, H1264, H1299, and Calu-6) after treatment with KRG extract fractions and constituents thereof were assessed using the water-soluble tetrazolium salt (WST-1) assay and terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, respectively. Caspase activation was assessed by detecting its surrogate marker, cleaved poly adenosine diphosphate (ADP-ribose) polymerase, using an immunoblot assay. The expression and subcellular localization of apoptosis-inducing factor were assessed using immunoblotting and immunofluorescence, respectively. Results and conclusion: Bioactivity-guided fractionation of the KRG extract revealed that its ethyl acetate-soluble fraction exerts significant cytotoxic activity against all human lung cancer cell lines tested by inducing apoptosis. Chemical investigation of the ethyl acetatesoluble fraction led to the isolation of six ginsenosides, including ginsenoside Rb1 (1), ginsenoside Rb2 (2), ginsenoside Rc (3), ginsenoside Rd (4), ginsenoside Rg1 (5), and ginsenoside Rg3 (6). Among the isolated ginsenosides, ginsenoside Rg3 exhibited the most cytotoxic activity against all human lung cancer cell lines examined, with $IC_{50}$ values ranging from $161.1{\mu}M$ to $264.6{\mu}M$. The cytotoxicity of ginsenoside Rg3 was found to be mediated by induction of apoptosis in a caspase-independent manner. These findings provide experimental evidence for a novel biological activity of ginsenoside Rg3 against human lung cancer cells.

• Journal of Korea Foresty Energy
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• v.23 no.2
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• pp.21-28
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• 2004

Three different strains of Lentinula edodes, Sanlim 5-Ho, Sanlim 6-Ho and Nongki 3-Ho, were cultured in the sawdust media of Mongolian oak(Quercu mongolica Fisch) for 90 days under dark and light conditions(each 30 days) and fruiting period(30 days). Weight loss of sawdust media was determined after fungal cultures and the contents of ergosterol in fungal mycelia were quantified by HPLC analysis followed by solvent extraction. Compared with the two other fungal strains$(8\%)$, weight loss of Sanlim 5-Ho was slightly lowered to $7\%$. The level of ergosterol content, a parameter for fungal growth, was continuously enhanced in Sanlim 5-Ho for dark and light incubation periods. However, Sanlim 6-Ho and Nongki 3-Ho recorded the maximized fungal growth under light condition. In fruiting periods the ergosterol contents were lowered in the three strains. Intra- and extracellular enzymes during cultural and fruiting periods were also characterized. The activity of Mn-peroxidase and laccase, which are characteristics enzymes for white rot fungi as lignin degrading enzymes, were determined as a high level overall the periods. As cellulose degrading indicators, the activity of CMCase, avicelase, xylanase and glucanase were detectable in initial incubation period.

• Korean Journal of Clinical Pharmacy
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• v.8 no.2
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• pp.122-132
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• 1998

SB-31 which contains Pursatilla, Licoris and Ginseng extracts was recently proved as an anticancer agent. In a preclinical effort to be applied this drug to human, pharmacokinetics of SB-31 was carried out in rats and rabbits. Glycyrrhizin(GZ), a saponin of Licoris was used as a standard ingradient for the pharmacokinetics of SB-31. The rat's blood, bile and urine samples were serially collected in femoral vein, common bile duct and bladder, respectively, after bolus i.v. injection at a dose of 1 or 1/5 ampul/rat and rabbit's blood samples from the marginal ear vein at a dose of 1 or 3 amp./rabbit. GZ and glycyrrhetic acid(GA), a major metabolite of GZ in the physiological samples were analysed by HPLC with UV detection. The decline of GZ in plasma concentration was generally biexponential at each dose. GZ was almost completely recovered in bile within 18 hour. GA wasn't detected in the samples with UV detector. In the rat, Vss and Kel at a dose of 1 and 1/5 ampul of SB-31 were $98.06\pm6.07\;ml,\;0.33\pm0.05\;hr^{-1}\;and\;65.46\pm11.19\;ml,\;0.68\pm0.25\;hr^{-1}$, respectively. Those in rabbits at a dose of 3 and 1 ampul of SB-31 were $235.24\pm30.72\;ml,\;0.13\pm0.36\;hr^{-1}\;and\;341.32\pm28.58\;ml,\;0.27\pm0.04\;hr^{-1}$, respectively. 'WinNonlin' was utilized for the compartmental analysis. A two-compartment model was chosen as the most appropriate pbarmaco-kinetic model. The data were best described by using a weighting factor of $1/y^2$. To evaluate the effect of SB-31 on cardiovascular system, serially diluted SB-31 was directly injected into coronary artery in the isolated perfused rat heart and the effect of PSF, PSH, saponins of Pursatilla, and SB-31 on PT, APTT of healthy human plasma was examined. Except the positive inotropic effect of ten times diluted solution of SB-31, there was no significant effect on LVDP, (- dp/dt)/(+dp/dt), heart rate and coronary flow in comparision with that of vehicle. SB-31 had no effect on PT but slightly delayed APTT about $6.9{\sim}11.5\%$. There was no significant effect of PSF and PSH on PT & APTT. Conclusively, SB-31 did not show any notable toxic effects on cardiovascular system.