• Journal of Pharmaceutical Investigation
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• v.38 no.3
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• pp.191-197
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• 2008

The purpose of the present study was to examine the pharmacokinetics and lymphatic delivery of the oligopeptide, a model peptide of X antigen epitope peptides, after the intramuscular administration of the peptide-bearing liposomes in rats. $^{14}C$-labelled peptide was used as a tracer to analyze the peptide levels in plasma, bile, urine, tissue homogenates, and lymph nodes (superior cervical nodes, brachial nodes and superior mesenteric nodes). Model peptide rapidly disappeared from the plasma by 30 min (${\alpha}$ phase) after i.v. administration, which was followed by the late disappearance. The apparent plasma half-lives ($t_{1/2({\alpha}),app}$) of the peptide at the ${\alpha}$ phase when administered at a dose of 0.2-1.0 mg/kg were about 5 min. The maximum plasma concentration ($C_{max}$) was $1.52\;{\mu}g/mL$, after the i.m. administration of the peptide at a dose of 1.0 mg/kg. The bioavailability, which was calculated from the time zero to last quantitative time, of the i.m. administered peptide was over 60%. Of the various tissues tested, the peptide was mainly distributed in the kidney after the i.m. administration. The peptide levels in the kidney 3 hr after the i.m. administration were higher than those of maximum plasma concentration ($C_{max}$). The cumulative amounts of the peptide found in the urine 72 hr after the administration of 1.0 mg/kg were 2-folder higher than those in the bile, suggesting that the peptide is mostly excreted in the urine. Moreover, the concentrations of the peptide in the lymph nodes were as high as that of the plasma and the tissues. In conclusion, the peptide concentration in the lymph nodes was maintained by 24 hr after the i.m. administration of the peptide-bearing liposomes.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.2
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• pp.318-322
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• 2014

5-Alpha reductase II, which converts testosterone (T) to dihydrotestosterone (DHT), is a crucial enzyme II in benign prostatic hyperplasia. Inhibitory effects of Curcuma longa L. (CL) extracts on 5-alpha reductase II activity were investigated in rat prostate tissue homogenates as well as LNCaP cells expressing human 5-alpha reductase II. Hot water extract (CL-HW) of Curcuma longa L. significantly inhibited 5-alpha reductase activity by over 80% at a concentration of $100{\mu}g/mL$, whereas 20% ethanol extracts (CL-E20) of Curcuma longa L. exhibited significant inhibitory activity from $50{\mu}g/mL$. These results indicated that Curcuma longa L is a potent 5-alpha reductase II inhibitor for benign prostatic hyperplasia treatment.

• Journal of Pharmaceutical Investigation
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• v.40 no.2
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• pp.101-107
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• 2010

A rapid and sensitive reversed-phase high performance liquid chromatography (HPLC) method was developed for the determination of N-(-4-Chlorophenyl)-6-hydroxy-7-methoxy-2-chromanecarboxamide (KAL-1120), a novel anti-inflammation agent, in the rat plasma. The method was applied to analyze the compound in the biological fluids such as bile, urine and tissue homogenates. After liquid-liquid extraction, the compound was analyzed on an HPLC system with ultraviolet detection at 275 nm. HPLC was carried out using reversed-phase isocratic elution with a $C_{18}$ column, a mobile phase of a mixture of acetonitril (40 v/v%) at a flow rate of 1.0 mL/min. The chromatograms showed good resolution and sensitivity and no interference of plasma. The calibration curve for the drug in plasma was linear over the concentration range of 0.05-50 ${\mu}g$/mL. The intra- and inter-day assay accuracies of this method ranged from 0.06% to 9.33% of normal values and the precision did not exceed 6.28% of relative standard deviation. The plasma concentration of KAL-1120 decreased to below the quantifiable limit at 1.5 hr after the i.v. bolus administration of 2-10 mg/kg to rats ($t_{1/2,({\alpha})}$ and $t_{1/2,({\beta})$ of 2.15 and 26.7 min at a dose of 2 mg/kg, 3.91 and 33.0 min at a dose of 10 mg/kg, respectively). The steady-state volume of distribution ($V_{dss}$) and the total body clearance ($CL_t$) were not significantly altered in rats given doses from 2 to 10 mg/kg. Of the various tissues tested, KAL-1120 was mainly distributed in the lung and heart after i.v. bolus administration. KAL-1120 was detected in the bile by 30 min after its i.v. bolus administration. However, the concentration in the urine after i.v. bolus administration became too low to measure, suggesting that KAL-1120 is mostly excreted in the bile. In conclusion, this analytical method was suitable for the preclinical pharmacokinetic studies of KAL-1120 in rats.

• Archives of Pharmacal Research
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• v.25 no.5
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• pp.655-663
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• 2002

Liver fibrosis is a prepathological state wherein damaged liver tissues in chronic liver diseases, such as hepatitis, are not repaired to normal tissues, but converted to fibrous tissue. 5-(2-Pyrazinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz), a cancer chemopreventive agent, is effective against a wide variety of chemical carcinogens. Recently, we reported that oltipraz inhibits liver fibrogenesis (Kang et al., 2002). In the present study, the effects of oltipraz in combination with dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (DDb) on dimethylnitrosamine (DMN)-induced liver fibrogenesis were assessed in rats. Oltipraz (30 mg/kg body weight, po, 3 times per week for 4 weeks) was found to inhibit the increases in plasma ALT, AST and bilirubin by DMN, whereas DDB (30 mg/kg body weight, po, 3 times per week for 4 weeks) attenuated the increases in the plasma ALT and bilirubin. The lowered plasma protein and albumin contents in DMN-treated rats were completely restored by oltipraz, but not by DDB. DDB decreases liver cell injury and inflammation through inhibition of nuclear factor-kB. DMN increased the accumulation of liver collagen, as indicated by the increase in the 4-hydroxyproline content in liver homogenates, which was reduced by treatment with oltipraz, but not by DDB. Given the differential effect between oltipraz and DDB, the potential enhancement of antifibrotic efficacy by the drugs was assessed in the animal model. Despite the minimal effect of DDB on DMN-induced fibrogenesis, DDB (5-25 mg/kg), administered together with oltipraz (25-5 mg/kg), showed an additive protective effect against hepatotoxicity and fibrosis induced by DMN, which was shown by the blood chemistry parameters and histopathological analysis. The adequate composition ratio of oltipraz to DDB was 5:1. These results provide information on the pharmaceutical composition, comprising of oltipraz and DDB as the active components, for the treatment and/or prevention of liver fibrosis and cirrhosis.

• Korean Journal of Food Science and Technology
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• v.37 no.6
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• pp.1018-1023
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• 2005

Simplified procedure was developed for concentrating and detecting poliovirus and norovirus in oysters. Viruses were seeded into oyster tissue homogenates and concentrated through polyethylene glycol (PEG) precipitation, chloroform or Freon extraction, with additional PEG precipitation. Amount of viruses was evaluated using poliovirus plaque assay. Virus recovery during concentration procedure was approximately 16.4-26.0%. For defection, viral RNAs in oysters were examined using one-step RT-PCR after extraction with Trizol. Dilution or capturing of viral RNA using silica gel membrane allowed viruses to be detected by RT-PCR, whereas viruses could not be removed using $QIAshredder^{TM}$ Homogenizer, which is effective in removing RT-PCR inhibitors in lettuce and hamburgers. Freon extraction, generally used to concentrate viruses found in food, could be substituted with chloroform extraction using this procedure; no difference could be observed between detection limits of whole oyster extracts and digestive organ extracts indicating that RT-PCR inhibitors were distributed evenly throughout whole tissues. Nested PCR greatly improved efficiency of this procedure. Overall, this procedure could remove sufficient amount of inhibitors to allow detection of norovirus in oysters.

• YAKHAK HOEJI
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• v.41 no.6
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• pp.737-748
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• 1997

Distribution of rhEGF in the skin, plasma and several organ tissues following topical application of $^{125}I-rhEGF$ (0.4${\mu}$Ci) solution in 25% Pluronic F-127 on 154$mm^2$ normal and damaged (burned and stripped) skins of hairless mice was examined. The radioactivity in the stripped skin tissues increased as a function of time, and was 10-20 times higher than that in the normal and burned skins. The fractions of intact drug in the skin tissues were 40-60% for the normal and burned skins, and 60-80% for the stripped skin. It indicates that the stratum corneum layer behaves as a barrier for the dermal penetration of the drug. The radioactivity in the plasma was much higher for the stripped skin than for the normal and burned skins. However, the concentration of intact drug in the stripped skin was comparable to those in the normal and burned skins indicating most severe degradation (or metabolism) of the drug in the stripped skin. As a result, the fraction of intact drug in the plasma was lowest for the stripped skin (<10%). Body organ distribution of the drug was much higher for the stripped skin. The concentration in the stomach. Both in total radioactivity and intact drug, showed more than 10-times higher value than in the other organs (liver, kidney and spleen). The fraction of intact drug in each organ tissue was below 10-20%. And generally lowest for the stripped skin. The lowest fraction of the drug for the stripped skin could not be explained by the activity of the aminopeptidases in the skin since it was lower for the stripped skin than for the normal skin. Thereover, the fraction of intact drug appears to be determined by the balance between dermal uptake and systemic elimination of the drug, for example. The mechanism of dermal uptake of rhEGF was examined by topical applying 200${\mu}$l of 25% Pluronic F-127 solution containing 0.4 ${\mu}$Ci of $^{125}I-rhEGF$ and 0.14${\mu}$Ci of $^{14}C$-inulin (a marker of passive diffusion). The radioactivity of $^{125}I-rhEGF$ at each sampling time point (0.5, 1, 2, 4 and 8hr) was correlated (p<0.05) with the corresponding radioactivity of $^{14}C$-inulin. It appears to indicate the rhEGF may be uptaken into the skins mainly by the passive diffusion. This hypothesis was supported by the constant specific binding of EGF to the skin homogenates regardless of the skin models. Receptor mediated endocytosis (RME) appears to contribute negligibly, if any, to the overall uptake process.

• Journal of Life Science
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• v.12 no.3
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• pp.349-356
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• 2002

In order to observe the bioactivity of ovariectomized rats, nonovariertoized (sham) group, ovariectomized (Ovx) group, ovariectomized ginseng total saponin (GTS)-treated (Ovx+ GTS) group and ovariectomized ginseng water extract (GW)-treated (Ovx+CW) group were made. We measured AST (L-aspartate aminotransferase) and ALT (L-alanin aminotransferase) in sera, and MDA (malondialdehyde:lipid peroxidation), SOD (superoxide dismutase), catalase, total-glutathione (GSH + GSSG) and GPx (glutathione peroxidase) in liver tissue total homogenates of rat. AST activity of serum in Ovx group was 2.11 times increased, but ALT activity was not changed compared to Sham group. In AST activity, they tend to decrease significantly in each substance such as GTS and GW administered group. Lipidperoxides of each fraction in Ovx group were highly increased compared to Sham group. Extracts of ginseng-treated group markedly inhibited lipid peroxidation by 62% ∼72%. And as the result of the measurements of SOD, catalase, total-glutathione and GPx which are antioxidant enzyme, antioxidant enzymes in Ovx group much lower than in Sham group. But they were significantly increased in each substance such as GTS and GW, administered group. Based on the results, it is supposed that more produced free radicals decreased antioxidant enzyme. And it is also thought that extracts of ginseng can inhibit aging by reducing antioxidant enzyme.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.1
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• pp.124-130
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• 2003

Effect of Korean red ginseng (KRG) on the level of serum and liver lipids and lipid peroxidation was investigated in the rats fed high fat diet. Content of serum total cholesterol was significantly decreased (P<0.05) in KRG I group and KRG II group. Content of HDL-cholesterol was significantly increased by 69.75% and 39.15% in KRG I and KRG II group compared to control group, respectively. Atherogenic index (hi) was also significantly decreased by 74.76% and 37.38% in KRG I and KRG II groups compared to control group, respectively. Serum triglyceride content was significantly decreased (p<0.05) in only KRG II group. Antioxidative activity of KRG on the lipid peroxidation of serum and tissues in rats was also studied in vivo by measuring the formation of thiobarbituric acid reactive substances (TBARS). Contents of TBARS in the serum of both KRG groups were significantly decreased (p<0.05) and that of nonheme iron in serum was significantly increased (p<0.05) in a dose-dependent manner, which suggested that lipid peroxidation contents are inversely correlated with serum nonheme iron content. Content of TBARS in liver was significantly decreased (p<0.05) in KRG I and KRG II groups, without any influence in other tissues. Content of TBIARS in liver microsomal fractions stimulated by Fe$^{2+}$/ascorbate was significantly decreased (p<0.05) in KRG I and KRG II groups, whereas this observation did not occur in liver mitochondrial fractions. When the effect of KRG on TBARS content in the liver fractions of homogenates, microsomes, and mitochodria stimulated by Fe$^{2+}$/ascorbate was tested in vitro experimental model, TBARS of liver three fractions was significantly decreased at 6 mg/mL KRG compared with those of control. These results suggested that KRG powder have hypocholesterolemic effect as well as antioxidative effect in the serum and liver of the rats fed high fat diet.

• The Korean Journal of Pharmacology
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• v.29 no.1
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• pp.85-96
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• 1993

To investigate the alteration of transferrin receptor (TfR) in the proliferating or transformed liver cells, $^{125}I-transferrin$ binding experiment was carried out in the isolated parenchymal cells (PC) or nonparenchymal cells (NPC) from normal regenerated rat liver after partial hepatectomy and from the liver of 3-methyl-4-dimethyl-aminoazobenzene (3-Me-DAB) treated rat. With the administration of 3-Me-DAB for 8 weeks, the liver tissue showed marked morphologic changes of oval cell proliferation, regenerations of hepatocytes, and atypical proliferations of bile ducts, but these changes were little affected by partial hepatectomy. Transferrin binding values in PC or NPC homogenate from the regenerated liver of normal rat, were increased by 3rd day and diminished to control level at 7th day after partial hepatectomy. With the treatement of 3-Me-DAB for 8 weeks, transferrin binding sites in homogenates were higher than those of normal rat liver and increased by 7th day after partial hepatectomy. Transferrin binding sites (Bmax) in the cell membrane of NPC were higher than those of PC of normal rat liver, but there was no significant difference in Kd values between both groups (5.05, 6.3 nM). In the normal resenerated rat liver, transferrin binding sites in the PC or NPC plasma membrane, were increased by 3rd day and diminished to control level at 7th day after partial hepatectomy. With 3-Me-DAB tratment, transferrin binding sites in both liver NPC and PC plasma membrane were increased about 3 folds, compared to those in each plasma membrane of normal rat liver. And after partial hepatectomy of 3-Me-DAB trated rat, transferrin binding sites were increased by the 3rd day in the NPC plasma membrane but increased by the 7th day in the PC plasma membrane. In the transferrin binding sites of the PC or NPC plasma membrane of 3-Me-DAB treated liver, two kinds of Kd values $(3.1{\sim}4.7\;nM,\;25.4{\sim}54.1\;nM)$ were detected. The present results suggest that 1) TfRs are distributed in the liver PC as well as NPC; 2) Increased TfRs in PC or NPC plasma membrane of normal regenerated liver after partial hepatectomy and 3-Me-DAB treated rat liver, may be due to increased intracellular synthesis; 3) Increased TfRs in normal regenerated liver after partial hepatectomy might be related to the expression of a single type of high affinity site $(Kd,\;3.1{\sim}7.5\;nM)$, but in 3-Me-DAB treated rat liver might be related to the expression of high and low affinity types of receptors $(Kd,\;25.4{\sim}54.1\;nm)$.