• Archives of Pharmacal Research
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• v.25 no.3
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• pp.293-299
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• 2002

Cytotoxic and antimutagenic effects of a novel cis-$\varepsilon$-viniferin and five known stilbenes, transresveratrol, trans-$\varepsilon$-viniferin, gnetin H, suffruticosols A and B, isolated from the seeds of Paeonia lactiflora Pall. (Paeoniaceae) were determined against five different cancer cell lines, and mutagenicity of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in Salmonella typhimurium TA100, respectively. Six stilbenes showed cytotoxic activity in a dose-dependent manner, and especially did potent cytotoxic activity against C6 (mouse glioma) cancer cell with $IC_{50}$ values ranging from 8.2 to $20.5{\;}{\mu\textrm{g}}/ml$. trans-Resveratrol showed significant cytotoxic activity against HepG2 (liver hepatoma) and HT-29 (colon) human cancer cell lines with $IC_{50}$ values of 11.8 and 25.2 g/ml, respectively. In contrast, trans-$\varepsilon$-viniferin and cis--viniferin, and gnetin H exhibited marked cytotoxic activity against Hela (cervicse) and MCF-7 (breast) human cancer cell lines with $IC_{50}$ values of 20.4, 21.5, and $12.9{\;}{\mu\textrm{g}}/ml$, respectively. However, suffruticosol A and B had less cytotoxic effect against all cancer cells except C6. Meanwhile, six stilbenes exerted antimutagenic activity in a dose-dependent fashion. Of them, trans-resveratrol exhibited the strongest antimutagenic effect against MNNG with $IC_{50}$ value of $27.0{\;}{\mu\textrm{g}}/plate$, while other five resveratrol oligomers also did moderate antimutagenic activity with $IC_{50}$ values ranging from 31.7 to $35.2{\;}{\mu\textrm{g}}/plate$.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.20 no.1
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• pp.1-13
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• 1994

An antioxidative compound was isolated from pine needles. This compound was identified as 4-hydroxy-5-methyl-3[2H]-furanone on the basis of spectroscopic evidences. It scavenged 1,1-diphenyl-2-picrylhydrazyl free radicals more efficiently than maltol and tocopherol did. It exhibited an inhibitory effect on the lipid peroxidation of rat liver microsome induced by Fe(ll)/ascorbate, and the protective effect against UV cytotoxicity in cultured human fibroblasts. In addition, HMF appeared to prevent the cellular melanogenesis in the cultured murine melanoma cells, more effectively than kojic acid, a well known inhibitor of melanogenesis, while the former was not so effective as the latter for the inhibilion of the tyrosinase. Considering that cellular melanogenesis is a metabolic process triggered by oxidative stress, it was tentatively deduced that the antioxidative property of HMF may afford the effect against cellular pigmentation by alleviating the causative stress. This study provided a novel inhibitor of melanogenesis, that might be useful for the cosmetic applications.

• Proceedings of the Ginseng society Conference
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• 1993.09a
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• pp.171-178
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• 1993

The effects of Korean Red Ginseng (KRG) in rats submitted to exhaustion exercise have been studied, by measuring different enzymatic and hematological parameters in plasma and muscle. KRG powder was daily administered to 15 male Wistar rats for a period of two weeks. Another group of 15 rats with the same characteristics were administered physiological saline. Both groups were divided as follows: 5 control. 5 exercised till exhaustion and 5 recovered for 48 h after exhaustion. The following results were obtained for the groups treated with KRG in rapport to those treated with saline: - Higher endurance to running, - Increase of the osmotic resistence of red blood cells and higher presence of reticulocytes. - Lower triglyceride levels in plasma. - Increase non statistically significant of urea levels in plasma, - Lower non statistically significant hypoglycemia after exhaustion exercise. - Decrease of liver glycogen after exercise and faster recovery of the resting - level. - Protective effect on tissular damage produced by exhaustion exercise - Lower LDH activity in all studied muscles. only statistically significant in the WG.

• Korean Journal of Organic Agriculture
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• v.19 no.4
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• pp.553-563
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• 2011

This experiment was conducted to determine the effect of nattokinase (NK) additives on milk production and composition, and blood metabolites in dairy cows. The two kinds of nattokinase with high fibrinolytic activity were produced by two strains of bacteria, Bacillus amyloliquefacines (NK1) and Bacillus subtilis (NK2). Total fifteen Holstein cows (average $1.83{\pm}0.37$ parity; average milk yield $23.2{\pm}3.2$ kg/d) were randomly assigned to three treatments (5 animals per treatment). Cows were fed TMR supplemented with 0g, 100g and 100g for control, NK1 and NK2 treatment, respectively for 4 weeks. Milk yield was significantly higher (p<0.05) for NK1 (22.89 kg/d) than for control (21.07 kg/d) and NK2 (21.36 kg/d). Somatic cell counts in NK treatments were significantly lower than that in control group (58,000 vs. 21,000 and 35,000 cells/ml, control vs. NK1 and NK2). Serum ALT levels in all treatment were similar to the range of 32.00~35.83 IU/L, but AST levels in NK1 (85.67 IU/L) was significantly decreased compared with those in control and NK2 (121.67 and 117.67 IU/L respectively). Serum T-CHO levels in NK1 (145.33 mg/dl) was significantly decreased (p<0.05) compared with that in control (179.00 mg/dl) and NK2 (176.17 mg/dl). This finding showed that NK1 additives could possibly have a positive effect in lactation performance of mid-lactation dairy cows by increasing milk yield, reducing somatic cell count, improving liver function and decreasing cholesterol in blood.

• Toxicological Research
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• v.20 no.1
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• pp.43-47
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• 2004

In order to investigate the safety of a water extract (ADP) of 1 : 1 mixture of Anemarrhena rhizoma and Phellodendron cortex for alleviating benign prostate hyperplasia, genotoxicity studies in bacterial and mammalian cell assay systems, namely, the Ames bacterial reverse mutation and chromosomal aberration assays were performed. As shown by the results of the Ames bacterial reversion assay, ADP in the range of 625-5000 $\mu\textrm{g}$/plate did not induce mutagenicity in Salmonella typhimurium TA 98, TA 100, TA 1535 and TA 1537 strains in the absence or in the presence of S9 (the microsomal fraction of rat liver homogenate) metabolic activation. The $IC_{50}$ (50% cell growth inhibition concentration) values of ADP for the chromosomal aberration assay were determined; these were 2425 $\mu\textrm{g}$/ml in the absence and 8126 $\mu\textrm{g}$/ml in the presence of S9 metabolic activation in Chinese hamster lung (CHL) fibroblast cell culture. No chromosomal aberration was observed in CHL cells treated with ADP at 2425, 1212.5 and 606.25 $\mu\textrm{g}$/ml in the absence, or at 8126, 4063 and 2031.5 $\mu\textrm{g}$/ml in the presence of S9 metabolic activation. These results show that under the conditions used, ADP does not harmfully affect the bacterial or mammalian cell system at the gene level.

• Biomolecules & Therapeutics
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• v.4 no.1
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• pp.19-31
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• 1996

This study was performed to determine the subacute toxicities of SKI306X, an antiinflammatory herbal extract, in rats. SKI306X was administered orally to rats once a day for 4 weeks at doses of 0.3, 1.0, and 3.0 g/kg/ day. Each group consisted of 20 male and 20 female rats, including 5 male and 5 female rats per group for an interim study at the end of 2-week administration and for a 2-week recovery study, respectively. Throughout the study, all rats survived and no adverse clinical signs were observed. Although male rats treated with high dose (3.0 g/kg/day) of SKI306X showed slight loss of body weight (approximately 5%) in comparison with control animals during the administration period, their body weight loss was normally restored during the recovery period. No significant change was found in all hematological parameters of SKI306X-treated groups except for the decreased number of red blood cells in all female groups at the interim study. Statistically significant changes were observed in several blood enzyme levels of SKI306X-treated groups; however, most of these significant changes were within normal range and statistically significant values did not show dose-related responses. In SKI306X-treated groups, the absolute and relative weights of liver, heart, and stomach were statistically different from those of control group, but these differences disappeared at the end of recovery period and also drug-related gross and histopathological findings in these organs were not found. No other drug-related gross and histopathological findings were observed. It is concluded from the results of this study that non-toxic dose of SKI306X was estimated to be between 0.3 and 1.0 g/kg/day and the maximum tolerated dose of SKI306X was assumed to be higher than 3.0 g/kg/day.

• Biomolecules & Therapeutics
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• v.19 no.2
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• pp.255-260
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• 2011

The purpose of this study was to investigate the effect of ticlopidine on the pharmacokinetics of diltiazem and its active metabolite, desacetyldiltiazem, in rats. Pharmacokinetic parameters of diltiazem and desacetyldiltiazem were determined in rats after oral administration of diltiazem (15 $mg{\cdot}kg^{-1}$) with ticlopidine (3 or 9 $mg{\cdot}kg^{-1}$). The effects of ticlopidine on P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A4 activities were also evaluated. Ticlopidine inhibited CYP3A4 enzyme activity in a concentrationdependent manner with a 50% inhibition concentration ($IC_{50}$) of 35 ${\mu}M$. In addition, ticlopidine did not significantly enhance the cellular accumulation of rhodamine-123 in NCI/ADR-RES cells overexpressing P-gp. Compared with the control (given diltiazem alone), ticlopidine significantly altered the pharmacokinetic parameters of diltiazem. The peak concentration ($C_{max}$) and the area under the plasma concentration-time curve (AUC) of diltiazem were significantly (9 $mg{\cdot}kg^{-1}$, p<0.05) increased in the presence of ticlopidine. The AUC of diltiazem was increased by 1.44-fold in rats in the presence of ticlopidine (9 $mg{\cdot}kg^{-1}$). Consequently, the absolute bioavailability (A.B.) of diltiazem in the presence of ticlopidine (9.3-11.5%) was signifi cantly higher (9 $mg{\cdot}kg^{-1}$, p<0.05) than that in the control group (8.0%). Although ticlopidine significantly (p<0.05) increased the AUC of desacetyldiltiazem, the metabolite-parent AUC ratio (M.R.) in the presence of ticlopidine (9 $mg{\cdot}kg^{-1}$) was significantly decreased compared to that in the control group, implying that ticlopidine could effectively inhibit the metabolism of diltiazem. In conclusion, the concomitant use of ticlopidine significantly enhanced the oral bioavailability of diltiazem in rats by inhibiting CYP3A4-mediated metabolism in the intestine and/or liver rather than by inhibiting intestinal P-gp activity or renal elimination of diltiazem.

• Parasites, Hosts and Diseases
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• v.48 no.4
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• pp.291-295
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• 2010

The onset, severity, and ultimate outcome of malaria infection are influenced by parasite-expressed virulence factors and individual host responses to these determinants, In both humans and mice, liver injury is involved after parasite entry, which persists until the erythrocyte stage after infection with the fatal strain Plasmodium falciparum (Pf), Hepatocyte growth factor (HGF) has strong anti-apoptotic effects in various kinds of cells, and also has diverse metabolic functions. In this work, Pf-subtilisin-like protease 2 (Pf-Sub2) 5' untranslated region (UTR) was analyzed and its transcriptional activity was estimated by luciferase expression. Fourteen TATA boxes were observed but only one Oct-1 and c-Myb were done. In addition, host HGF interaction with Pf-Sub2 was evaluated by co-transfection of HGF- and Pf-Sub2-cloned vector. Interestingly, -1,422/+12 UTR exhibited the strongest luciferase activity but -329 to + 12 UTR did not exhibit luciferase activity. Moreover, as compared with the control of unexpressed HGF, the HGF protein suppressed luciferase expression driven by the 5' untranslated region of the Pf-Sub2 promoter. Taken together, it is suggested that HGF controls and interacts with the promoter region of the Pf-Sub2 gene.

• Biomolecules & Therapeutics
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• v.21 no.6
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• pp.487-492
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• 2013

Cytochrome P450 4A11 (CYP4A11) is a fatty acid hydroxylase enzyme expressed in human liver. It catalyzes not only the hydroxylation of saturated and unsaturated fatty acids, but the conversion of arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), a regulator of blood pressure. In this study, we performed a directed evolution analysis of CYP4A11 using the luminogenic assay system. A random mutant library of CYP4A11, in which mutations were made throughout the entire coding region, was screened with luciferase activity to detect the demethylation of luciferin-4A (2-[6-methoxyquinolin-2-yl]-4,5-dihydrothiazole-4-carboxylic acid) of CYP4A11 mutants in Escherichia coli. Consecutive rounds of random mutagenesis and screening yielded three improved CYP4A11 mutants, CP2600 (A24T/T263A), CP2601 (T263A), and CP2616 (A24T/T263A/V430E) with ~3-fold increase in whole cells and >10-fold increase in purified proteins on the luminescence assay. However, the steady state kinetic analysis for lauric acid hydroxylation showed the significant reductions in enzymatic activities in all three mutants. A mutant, CP2600, showed a 51% decrease in catalytic efficiency ($k_{cat}/K_m$) for lauric acid hydroxylation mainly due to an increase in $K_m$. CP2601 and CP2616 showed much greater reductions (>75%) in the catalytic efficiency due to both a decrease in $k_{cat}$ and an increase in Km. These decreased catalytic activities of CP2601 and CP2616 can be partially attributed to the changes in substrate affinities. These results suggest that the enzymatic activities of CYP4A11 mutants selected from directed evolution using a luminogenic P450 substrate may not demonstrate a direct correlation with the hydroxylation activities of lauric acid.

• Journal of Veterinary Clinics
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• v.5 no.1
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• pp.43-52
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• 1988

These studies were taken experimentally to clarify the clinical and histopathological findings of listeriosis in Korean native goat(KNC). Four KNGs of 4 to 5 months of age were inoculated orally or in-travenously (IV) with Listeria monocytogenes isolated from a field case of KNG. 1. On the clinical findings, depression, anorexia and fever were observed in all inoculated goats, and nasal discharge, keratoconjunctivitis and diarrhea in 3 of 4 goats. Highest rectal temperature after in-oculation was 2.5$^{\circ}C$ higher in IV inoculated goats and 1.9$^{\circ}C$ higher in orally inoculated than normal rectal temperature observed before inoculation. Durations of clinical course after inoculation in IV and orally inoculated goats were 5 days and 8 days, respectively. 2. On the gross lesions, swelling of the lymph nodes, hemorrhage and .inflammation of the small intestine and rigor mortis were observed in 4 of 4 goats, and keratoconjunctivitis, hemorrhage and inflammation of the large intestine, swelling of the spleen, pneumonia and hydropericardium in 3 of 4 goats. Congestion of the visceral organs and ecchymosis of the sin in a fetus were observed. Keratoconjunctivitis, hemorrhage of the abomasum, swelling of the lymph node, hemorrhage and inflammation of the small intestine, swelling of the spleen, necrosis of the liver and pneumonia were observed as severe lesions. These lesions were more severe in IV inoculated goats than those in orally inoculated goats. 3. On histopathological findings, focal necrosis found throughout the livers occurred mainly on peripheral areas of hepatic lobules. These necrotic foci consisted of neutrophils, lymphocytes, macrophages, short rod bacteria and necretic hepatic cells. Suppurative pneumonia of the lung, hyperemia, congestion, epithelial necrosis and sloughing of the small and large intestine, swelling in periventricular regions of the central nervous system, swelling of the kidney, spleen and lymph node were observed as listerial lesions.