• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2823-2828
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• 2012

Objective: To explore a new model of in-situ xenograft lymphangiogenesis of human colonic adenocarcinomas in nude mice. Method: On the basis of establishing subcutaneous xenograft lymphangiogenesis model of human colonic adenocarcinoms, in-situ xenografts were established through the in situ growth of the HT-29 human colonic adenocarcinoma cell line in nude mice. The numbers of lymphangiogenic microvessels, the expression of lymphatic endothelial cell markers lymphatic vessel endothelial hyaloronic acid receptor-1 (LYVE-1), D2-40 and the lymphatic endothelial growth factors vascular endothelial growth factor-C (VEGF-C), -D (VEGF-D) and receptor-3 (VEGFR-3) were compared by immunohistochemical staining, Western bolt and quantitative RT-PCR in xenograft in-situ models. Results: Some microlymphatics with thin walls, large and irregular or collapsed cavities and increased LMVD, with strong positive of LYVE-1, D2-40 in immunohistochemistry, were observed, identical with the morphological characteristics of lymphatic vessels and capillaries. Expression of LYVE-1 and D2-40 proteins and mRNAs were significantly higher in xenograpfts in-situ than in the negative control group(both P<0.01). Moreover, the expression of VEGF-C, VEGF-D and VEGFR-3 proteins and mRNAs were significantly higher in xenografts in-situ (both P<0.01), in conformity with the signal regulation of the VEGF-C,-D/VEGFR-3 axis of tumor lymphangiogenesis. Conclusions: In-situ xenografts of a human colonic adenocarcinoma cell line demonstrate tumor lymphangiogenesis. This novel in-situ animal model should be useful for further studying mechanisms of lymph node metastasis, drug intervention and anti-metastasis therapy in colorectal cancer.

• Journal of Pharmaceutical Investigation
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• 제40권1호
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• pp.15-21
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• 2010

Sibutramine is an orally administered centrally-acting antiobesity agent and inhibits both noradrenaline(norephinephirine) and serotonin(5-HT) reuptake. These effects are contributed by its active metabolites, M1 and M2. However, as the free base form of sibutramine is an oil form in room temperature, it had the problem of handling and stability. Thus, this drug should be used in the form of acid salt form in the pharmaceutical application. Unfortunately, anhydrous sibutramine hydrochloride is highly hygroscopic and unstable. In order to solve the hygroscopicity of the anhydrous salt form, another sibutramine acid salt form must be developed as a hydrate form. In this study. to overcome these problems, various of sibutramine acid salt forms were prepared with the pharmaceutically available salts such as maleate, esylate, mandelate, camsylate, besylate, salicylate, tartrate, isethionate and malate forms, and their physicochemical properties were investigated. Sibutramine malate was selected for excellent solubility and stability among the listed salt forms above. Its pharmacokinetic parameters were evaluated in rats comparing with sibutramine HCl, resulting in similar parameters. In vitro dissolution study of sibutramine malate-loaded capsule was performed comparison with commercial product ($Reductil^{(R)}$) in pH 1.2, pH 4.0, pH 6.8 and water medium. Our results indicated that there were no significant differences in their dissolution profiles were similar in all tested medium. Thus, sibutramine malate-loaded capsule should be a potential candiate due to its excellent solubility, good stability and biosimilar absorption.

• The Journal of Korean Medicine
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• 제23권2호
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• pp.97-107
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• 2002

Objective : Acupuncture is a method used to treat many kinds of pain in oriental cultural medicine. Especially when hetero-segmental area acu-points are stimulated, the therapeutic effects of pain control have more critical properties than other methods of acupuncture. However, the mechanism of pain control by acupuncture is contradictory so far. The present study examined the effects of electroacupuncture (EA) applied to the acu-point of the hetero-segmental area on modulation of formalin-induced pain in Sprague-Dawley rats. Methods : In order to apply EA to acu-points in the plantar area of right forepaws, a pair of Teflon-coated stainless steel wires were implanted in HT 7 (Shin-Moon) and PC 7 (Dae-Reung) 7 days before the behavioral test. A behavioral test was performed by means of video camera after injection of 5% formalin ($50{\;}\mu\textrm{l}$) into the lateral plantar region of the left hind paw. EA was delivered by a constant DC current stimulator at 4~5 mA, 2 ms, and 10 Hz for 30 min. c-Fos protein expression was measured in the lumbar spinal cord at 2 hr and 4 hr after formalin injection. Results : Behavioral responses including favoring, flinching and biting occurred in the biphasic pattern, such as the 1st phase (0~5 min) and the 2nd phase (20~45 min) after formalin injection. However, EA (4~5 mA, 2 ms, 10 Hz) significantly inhibited the behavioral responses. Injection of formalin expressed c-Fos protein on the ipsilateral dorsal horn neurons in L3 - L5 and the expression was sustained more than 4 hrs after formalin injection. However, EA decreased c-Fos protein expression at dorsal horn neurons in the lumbar spinal cord till 4hrs after formalin injection. Conclusions : These results suggest that EA modulates formalin-induced pain and this inhibitory action may be elicited by the descending inhibitory system.

• Korean Journal of Medicinal Crop Science
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• 제22권5호
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• pp.369-377
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• 2014

In order to find out anticancer activity of Korean pepper (Capsicum annuum L.), the cytotoxicity against 8 cell lines including 293 (normal kidney cells) and A-431 (epidermoid carcinoma cells) of extracts by extraction solvents and plant parts were investigated using MTT assay. Also the correlation between content of capsaicin known as anticancer ingredient and cytotoxicity of extracts from pepper were analyzed. The distilled water extracts from seed and germinated seed showed very high cytotoxicity against 6 cancer cell lines including A549 (lung carcinoma cells), AGS (stomach adenocarcinoma cells), HeLa (cervix adenocarcinoma cells), HepG2 (hepatoblastoma cells), HT-29 (colon adenocarcinoma cells), and MCF-7 (breast adenocarcinoma cells). But 80% ethanol and methanol extracts showed cytotoxicity against 293 and AGS. The $RC_{50}$, that was, the concentration of sample required for 50% reduction of cell viability, of seed and germinated seed extracts against AGS were $33.4{\sim}389.1{\mu}g/m{\ell}$ and $63.9{\sim}1,316.7{\mu}g/m{\ell}$, respectively, so anticancer activity was higher in seed than in germinated seed. In capsaicin contents, seed with high cytotoxicity and pericarp with a little cytotoxicity contained $47.4{\sim}1,260.0{\mu}g/g$ and $58.3{\sim}1,498.0{\mu}g/g$, respectively. As these results, the correlation was not between cytotoxicity and capsaicin content.

• Preventive Nutrition and Food Science
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• 제20권3호
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• pp.153-161
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• 2015

Matrix metalloproteinases (MMPs) are crucial extracellular matrices degrading enzymes that have important roles in metastasis of cancer progression as well as other significant conditions such as oxidative stress and hepatic fibrosis. Marine plants are on the rise for their potential to provide natural products that exhibit remarkable health benefits. In this context, brown algae species have been of much interest in the pharmaceutical field with reported instances of isolation of bioactive compounds against tumor growth and MMP activity. In this study, eight different brown algae species were harvested, and their extracts were compared in regard to their anti-MMP effects. According to gelatin zymography results, Ecklonia cava, Ecklonia bicyclis, and Ishige okamurae showed higher inhibitory effects than the other samples on MMP-2 and -9 activity at the concentrations of 10, 50, and $100{\mu}g/mL$. However, only I. okamurae was able to regulate the MMP activity through the expression of MMP and tissue inhibitor of MMP observed by mRNA levels. Overall, brown algae species showed to be good sources for anti-MMP agents, while I. okamurae needs to be further studied for its potential to yield pharmaceutical molecules that can regulate MMP-activity through cellular pathways as well as enzymatic inhibition.

• Journal of Ginseng Research
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• 제22권1호
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• pp.22-31
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• 1998

Antiulcer effects of ginseng saponin, acidic polysaccharide and methanol extract of Panax ginseng in the patients and experimental animals were reported. Postulated action mechanisms of ginseng were histamine-Ht receptor blocking and increasing gastric blood flow In the present study, the effect of ginsenosides, the biologically active glycosides of ginseng, on gastric acid secretion was examined using gastric cells isolated from human and rabbit gastric mucosa. Ginseng saponin, ginsenoside $Rb_1$, $Rb_2$, $Rg_1$ and $Rh_2$ were tested in unstimulated as well as stimulated gastric cells. Histamine ($10^4$M) and 3-isobutyl-1-methylxanthine ($10^4$M) were used as secretagogues. To investigate the mechanism of ginsenosides on acid secretion, the levels of cAMP and cGMP were monitored in gastric cells. As a result, high concerltration(1mg/ml) of ginseng saponin showed 73-75% of stimulated acid secretion in control gastric cells. However, ginseng saponin had no effect on unstimulated acid secretion and the levels of cGMP and cAMP in gastric cells. Ginsenoside $Rb_1$, $Rb_2$ and $Rh_2$ significantly inhibited stimulated acid secretion. Gastric cGMP levels were increased by all ginsenosides tested while cAMP levels were increased by all ginsenosides in unstimulated state of gastric cells, but increased by ginsenosides ginsenoside $Rg_1$ and $Rh_2$in stimulated state of gastric cells. The results suggest that inhibition of ginseng saponin on gastric acid secretion represents a complex effect of individual ginsenosides, which produce a range of effect on acid secretion. The inhibition site of ginseng saponin on stimulated acid secretion is postulated as post cAMP levels in acid secretary pathway such as protein phosphorylation or proton pump. Nitric oxide may not be involved in the inhibitory effect of ginseng saponin on stimulated acid secretion.

• Ocean and Polar Research
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• 제43권3호
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• pp.113-126
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• 2021

In the present study, the halophyte C. falcatum extract and its solvent fractions (n-hexane, 85% aqueous methanol, n-butanol, and water) were evaluated for antioxidant and anti-inflammatory activities. Antioxidative ability was measured by DPPH radical, intracellular reactive oxygen species (ROS) and peroxynitrite scavenging, DNA oxidation inhibition, and ferric reducing antioxidant power (FRAP). For DPPH radical and peroxynitrite scavenging, DNA oxidation inhibition, and FRAP, 85% aq.MeOH and n-BuOH fractions showed significant scavenging activity. For production of intracellular ROS in HT-1080 cells, 85% aq.MeOH fraction showed the highest scavenging activity. In addition, anti-inflammatory activity was also assessed by measuring the inhibitory effect against mRNA expression of pro-inflammatory factors (NO, IL-1β, IL-6 and COX-2) in LPS-stimulated Raw 264.7 macrophages. For NO production, crude extract exhibited a strong inhibitory effect at a concentration of 100 ㎍/ml. For mRNA expression of pro-inflammatory cytokines (IL-1β, IL-6, and COX-2), n-BuOH greatly suppressed expression levels of IL-1β and IL-6 at 100 ㎍/ml concentration while 85% aq. MeOH fraction significantly inhibited that of COX-2 even at 100 ㎍/ml. These results suggest that C. falcatum may be used as a potential source for the development of a natural antioxidant or anti-inflammatory agent.

• Korean Journal of Ichthyology
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• 제29권3호
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• pp.165-175
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• 2017

To minimize the damage caused by summer season such as high temperature and red tide, this study was conducted to investigate the effect of feeding and starvation on the survival rate, growth, growth restoration and physiological response of red seabream Pagrus major which were reared in marine net cage ($6m{\times}6m{\times}6m$). The feeding group was fed throughout the experiment for 10 weeks, whereas starvation group was not fed for 6 weeks and subsequent refeeding for 4 weeks. Survival rates of feeding and starvation groups were 94.4% and 98.1% respectively. The growth rate of starvation group was significantly lower than feeding group during starvation period, but recovered rapidly after feeding. The nutritional status such as albumin, total protein, total cholesterol, triglyceride also showed similar tendency to the growth data. Hematocrit and hemoglobin levels were higher in the feeding group than the starvation group during starvation period. Aspartate aminotransferase, glucose and total cholesterol were rapidly increased at the same time (in 5 week) in feeding group, whereas starvation group did not significant difference during starvation period. It was shown that the feeding group is more sensitive to stress than the starvation group. Thus, starvation can be applied as a rearing management plan of net cage fish farm in summer season.

• Korean Journal of Medicinal Crop Science
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• 제18권6호
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• pp.409-415
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• 2010

In this study, the bioactivities of ethanol (EELS) and water extract (WELS) from the leaf of Lythrum salicaria L. were investigated. In the anti-cancer activity, the growths of both human prostate cancer (DU145) and human colonic carcinoma cell (HT29) were inhibited up 60% by adding 10 mg/$m{\ell}$ of EELS. Anti-inflammatory activity of EELS and WELS have been evaluated on lipopolysaccharide (LPS) induced release of nitric oxide (NO) by the macrophage RAW 264.7 cells. EELS and WELS inhibited inflammatory by 57.3 and 46.9% in 10 mg/$m{\ell}$, respectively. In the anti-oxidative activity, $IC_{50}$ of DPPH radical scavenging activity was respectively 60.71 and $92.90\;{\mu}g/m{\ell}$ by EELS and WELS. In the anti-diabetic activity, $IC_{50}$ of ${\alpha}$-amylase inhibitory activity of EELS and WELS were respectively 5,250 and $5,020\;{\mu}g/m{\ell}$. $IC_{50}$ of ${\alpha}$-glucosidase inhibitory activity was 7.96 and $68.41\;{\mu}g/m{\ell}$ by EELS and WELS. In the anti-obesity, $IC_{50}$ of lipase inhibitory activity was 880 and $9,840\;{\mu}g/m{\ell}$ by EELS and WELS. Finally, EELS and WELS exhibited anti-oxidative, anti-inflammatory, anti-diabetic activity and anti-obesity. It suggests that Lythrum salicaria L. could be potentially used as a resource of bioactive materials for health functional foods.

• The Korean Journal of Mycology
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• 제39권1호
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• pp.68-77
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• 2011

80% methanol and 0.9% neutral saline soluble and hot water substances (hereinafter referred to Fr. NaCl, Fr. HW and Fr. MeOH, respectively) were extracted from fruiting bodies of Grifola frondosa. In vitro cytotoxicity tests, crude polysaccharides were not cytotoxic against cancer cell lines such as Sarcoma 180 and RAW 264.7 at the concentration of 10~2000 ${\mu}g/ml$, but crude polysaccharides from Fr. NaCl was slightly toxic to HT-29 and NIH3T3 at the concentration of 2000 ${\mu}g/ml$. Intraperitoneal injection with crude polysaccharides exhibited life prolongation effect of 25.0~52.9% in mice previously inoculated with Sarcoma 180. Fr. HW increased the numbers of spleen cells by 1.3 fold at the concentration of 200 ${\mu}g/ml$ compared with control. Fr. NaCl improved the immuno-stimulating activity of B lymphocyte by increasing the alkaline phosphatase activity by 1.5 fold compared with control at the concentration of 200 ${\mu}g/ml$. 10~14 ${\mu}M$ of nitric acid were generated when Fr. NaCl was added to RAW 264.7 at the concentration of 50~500 ${\mu}g/ml$, while the control group produced 4.3 ${\mu}M$ of nitric oxide. The Fr. NaCl, Fr. HW and Fr. MeOH increased the production of TNF-${\alpha}$, IL-$1{\beta}$, Il-2 and IL-6 by more than 1.4 times compared with the control group. The Fr. of MeOH increased the numbers of peritoneal exudate cells and circulating leukocytes by 3.0 and 2.0 folds compared with the control at the concentration of 50 ${\mu}g/ml$, respectively. Therefore, the crude polysaccharides extracted from fruiting bodies of Grifola frondosa could improve antitumor activity of mice.