Suigen, South Korea
Suigen, South Korea

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Son H.J.,Life Science Randnter | Jung K.,Korea University | Park Y.H.,Life Science Randnter | Jeon H.J.,Life Science Randnter | And 6 more authors.
Archives of Pharmacal Research | Year: 2015

We evaluated the effect of SKI3246, the 50 % ethanol extract of the rhizome of Atractylodes japonica, on visceral hypersensitivity, which is a major characteristic feature of IBS. We used various rat models of visceral hypersensitivity to assess the visceral pain responses to colorectal distension (CRD) in comparison with conventional IBS treatments. Oral administration of SKI3246 dose-dependently and significantly attenuated the abdominal withdrawal reflex (AWR) score in a model of acetic acid-induced visceral hypersensitivity. We also found that it reduced the number of abdominal contractions in response to CRD in a model of 2,4,6-trinitrobenzenesulfonic acid-induced visceral hypersensitivity, which was comparable to ramosetron or alosetron. Furthermore, treatment with SKI3246 also increased the pain threshold and abolished the elevated AWR scores to CRD in a rat model of neonatal maternal separation. We presumed that the modulation of the NK2 receptor is involved in the inhibitory activity of SKI3246 on the basis that it significantly inhibited the contraction of the distal colonic muscle induced by neurokinin A, the NK2 receptor agonist. The present results indicate that SKI3246 has the potential to be an effective therapeutic agent for IBS, especially insofar as it can relieve visceral hypersensitivity. © 2014 The Pharmaceutical Society of Korea.


Lim J.H.,Seoul National University | Kim J.-H.,Life Science Randnter | Kim N.,Seoul National University | Lee B.H.,Seoul National University | And 8 more authors.
Gut and Liver | Year: 2014

Background/Aims: The major compounds of Cochinchina momordica seed extract (SK-MS10) include momordica saponins. We report that the gastroprotective effect of SK-MS10 in an ethanol-induced gastric damage rat model is mediated by suppressing proinflammatory cytokines and downregulating cytosolic phospholipase A2 (cPLA2), 5-lipoxygenase (5-LOX), and the activation of calcitonin gene-related peptide. In this study, we evaluated the gastroprotective effects of SK-MS10 in the nonsteroidal anti-inflammatory drug (NSAID)-induced gastric damage rat model. Methods: The pretreatment effect of SK-MS10 was evaluated in the NSAID-induced gastric damage rat model using aspirin, indomethacin, and diclofenac in 7-week-old rats. Gastric damage was evaluated based on the gross ulcer index by gastroenterologists, and the damage area (%) was measured using the MetaMorph 7.0 video image analysis system. Myeloperoxidase (MPO) was measured by enzyme-linked immunosorbent assay, and Western blotting was used to analyze the levels of cyclooxygenase (COX)-1, COX-2, cPLA2, and 5-LOX. Results: All NSAIDs induced gastric damage based on the gross ulcer index and damage area (p<0.05). Gastric damage was significantly attenuated by SK-MS10 pretreatment compared with NSAID treatment alone (p<0.05). The SK-MS10 pretreatment group exhibited lower MPO levels than the diclofenac group. The expression of cPLA2 and 5-LOX was decreased by SK-MS10 pretreatment in each of the three NSAID treatment groups. Conclusions: SK-MS10 exhibited a gastroprotective effect against NSAID-induced acute gastric damage in rats. However, its protective mechanism may be different across the three types of NSAID-induced gastric damage models in rats.


Jung K.,Seoul National University | Jung K.,Life Science Randnter | Chin Y.-W.,Dongguk University | Yoon K.D.,Catholic University of Korea | And 4 more authors.
Immunopharmacology and Immunotoxicology | Year: 2013

Two triterpenoidal saponins were isolated from the seeds of Momordica cochinchinensis Sprenger (Cucurbitaceae). Identification of chemical structures has been performed by 1H- and 13C-NMR spectroscopy and gas chromatography (GC). One of the saponins is a new gypsogenin glycoside, named as gypsogenin 3-O-β-D-galactopyranosyl(1→2)-[α-L- rhamnopyranosyl(1→3)]-β-D-glucuronopyranoside (compound 1), which is reported for the first time from natural resources. The other saponin is a quillaic acid glycoside (compound 2), which showed anti-inflammatory activities in RAW 264.7 cells. The mechanistic understanding of anti-inflammatory activities demonstrates that compound 2 inhibits lipopolysaccharide-induced expression of nitric oxide and IL-6 via NF-κB pathway. © 2012 Informa Healthcare USA, Inc.


Jung K.,Seoul National University | Jung K.,Life Science Randnter | Chin Y.-W.,Dongguk University | Chung Y.H.,Chung - Ang University | And 5 more authors.
Immunopharmacology and Immunotoxicology | Year: 2013

Momordicae Semen, Momordica cochinchinensis Springer (Cucurbitaceae), has long been known to effectively relieve boils, rheumatic pain, and hemorrhoids. In this study, we investigated whether Momordicae Semen extract (MSE) has anti-gastritis effects in various rodent models and also explored possible mechanisms for the gastroprotective effects of MSE. MSE provided remarkable protective effects, comparable to those of rebamipide, in ethanol- and diclofenac-induced acute gastritis. In addition, it has demonstrated protective effect in a Helicobacter pylori-insulted chronic gastritis model. MSE also showed wound healing effect on cutaneous injury of mice and stimulated calcitonin gene-related peptide and somatostatin receptors, which may be related to its anti-gastritis effects. In a single oral dose toxicity study, the approximate lethal dose of MSE was determined at >2000mg/kg/day. The NOAEL was set to be 2000mg/kg/day from the repeated oral dose toxicity study. Moreover, momordica saponin I, a major ingredient of MSE, treatment decreased gastric mucosa damage indices in the ethanol- and diclofenac-induced acute gastritis models. The results suggest that MSE could be a promising gastroprotective herbal medicine and momordica saponin I might be used as an active marker compound for MSE. © 2012 Informa Healthcare USA, Inc.


Yoo H.,Seoul National University | Yoo H.,Life Science Randnter | Chae H.-S.,Dongguk University | Kim Y.-M.,Dongguk University | And 6 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2014

Three new compounds (1-3) and 20 known compounds were isolated from the rhizomes and roots of Sophora tonkinensis, and all the isolates were tested for their inhibitory activity against IL-6 production in HMC-1 cells stimulated by PMA plus ionophore, A23187. Of the tested compounds, compounds 1, 5, 9, and 21 were found to potently inhibit IL-6 production with IC50 values of 1.62, 0.73, 3.01, and 4.02 μM, respectively. © 2014 Elsevier Ltd.


Seo J.-S.,Ewha Womans University | Baek I.-S.,Ewha Womans University | Leem Y.-H.,Ewha Womans University | Kim T.-K.,Ewha Womans University | And 4 more authors.
Brain Research | Year: 2011

SK-PC-B70M, an oleanolic-glycoside saponins fraction extracted from the root of Pulsatilla koreana, carries active ingredient(s) that protects the cytotoxicity induced by Aβ(1-42) in SK-N-SH cells. It was recently demonstrated that SK-PC-B70M improved scopolamine-induced deficits of memory consolidation and spatial working memory in rats, and reduced Aβ levels and plaque deposition in the brains of the Tg2576 mouse model of Alzheimer disease. In the present study, we investigated whether SK-PC-B70M produces helpful effects on the pathology of the G93A-SOD1 transgenic mouse model of amyotrophic lateral sclerosis (ALS). Administration of SK-PC-B70M (100 or 400 mg/kg/day) from 8 weeks to 16 weeks of age attenuated neurological deficits of G93A-SOD1 mice in several motor-function-related behavioral tests. SK-PC-B70M treatment significantly suppressed the accumulation of the by-products of lipid peroxidation, malonedialdehyde (MDA) and 4-hydroxy-2-nonenal (HNE), in the spinal cord of G93A-SOD1 mice. Moreover, histologic analysis stained with cresyl violet or anti-choline acetyltransferase (ChAT) revealed that SK-PC-B70M suppressed neuronal loss in the ventral horn of the spinal cords of G93A-SOD1 mice. These results suggest that SK-PC-B70M affords a beneficial effect on neurologic deficits of G93A-SOD1 ALS mice. © 2010 Elsevier B.V. All rights reserved.


Ryu J.H.,Life Science Randnter | Ryu J.H.,Seoul National University | Kim S.,Life Science Randnter | Han H.Y.,Life Science Randnter | And 5 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2015

Synthesis of a series of 6-substituted picolinamide derivatives and their inhibitory activities against 11β-hydroxysteroid dehydrogenase type 1 are described. Optimization of the initial hit compound, N-cyclohexyl-6-(piperidin-1-yl)picolinamide (1) from high throughput screening of in-house library resulted in the discovery of the highly potent and metabolically stable compound 25, which was efficacious in a mouse ex vivo pharmacodynamic model and reduced the fasting blood glucose and insulin levels in a HF/STZ mouse model after oral dosing. © 2014 Elsevier Ltd. All rights reserved.


Jung K.,Seoul National University | Kim J.-S.,Life Science Randnter | Kim T.-H.,Incheon National University | Kim J.,Seoul National University
Helvetica Chimica Acta | Year: 2013

Enantiomerically pure (+)-(S)-clopidogrel was prepared by solid-phase synthesis using the commercially available Wang resin. This method offers mild reaction conditions and provides the (+)-(S)-clopidogrel in overall 52% yield over six steps and with optical purity of 98.0% ee. Copyright © 2013 Verlag Helvetica Chimica Acta AG, Zürich, Switzerland.


Seo P.J.,Seoul National University | Kim N.,Seoul National University | Kim J.-H.,Life Science Randnter | Lee B.H.,Seoul National University | And 7 more authors.
Gut and Liver | Year: 2012

Background/Aims: Aging gastric mucosa is known to have decreased mucosal defenses and increased susceptibility to injury by nonsteroidal anti-infl ammatory drugs. Depending on the type of nonsteroidal anti-infl ammatory drug (NSAID), the underlying mechanisms and the extent of damage to the stomach or intestine may differ. This study was performed to evaluate the acute gastric damage caused by different doses of indomethacin, diclofenac and aspirin in rats of various ages. Methods: For the acute models, indomethacin (10, 20 or 40 mg/kg), diclofenac (40 or 80 mg/kg) or aspirin (100 mg/kg) was given to 7- and 25-week-old and 1-year-old Sprague-Dawley rats by intragastric gavage. The gross ulcer index, damage area as assessed by imaging, histological index, myeloperoxidase (MPO) activity, and cytosolic phospholipase A2 (cPLA2) levels were measured after 24 hours. Results: The gross ulcer index and damage area increased with age in the presence of three NSAIDs (p<0.05). The increases in MPO levels induced by diclofenac and aspirin were signifi cantly higher in 1-year-old than 7-week-old rats (p<0.05). cPLA2 expression induced by indomethacin (10 and 40 mg/ kg) was greater in the 1-year-old rats, compared with 7-weekold rats (p<0.05). Conclusions: NSAID-induced acute gastric damage increased in a dose- and age-dependent manner.


Shin C.M.,Seoul National University | Kim N.,Seoul National University | Kim Y.S.,Wonkwang University | Nam R.H.,Seoul National University | And 8 more authors.
Gut and Liver | Year: 2016

Background/Aims: To evaluate changes in gut microbiota composition following long-term proton pump inhibitor (PPI) treatment. Methods: Twenty-four-week-old F344 rats were fed diets with (n=6) or without (n=5) lansoprazole for 50 weeks. Profiles of luminal microbiota in the terminal ileum were then analyzed. Pyrosequencing of the 16S rRNA gene was performed using an FLX genome sequencer (454 Life Sciences/Roche). Results: Rats treated with lansoprazole showed significantly reduced body weights compared to controls (lansoprazole-treated rats and controls, 322.3±15.3 g vs 403.2±5.2 g, respectively, p<0.001). However, stool frequencies and consistencies did not differ between the two groups. The composition of the gut microbiota in lansoprazole- treated rats was quite different from that of the controls. In the controls, the microbiota profiles obtained from the terminal ileum showed a predominance of Proteobacteria (93.9%) due to the abundance of Escherichia and Pasteurella genera. Conversely, lansoprazole-treated rats showed an elevated population of Firmicutes (66.9%), which was attributed to an increased ratio of Clostridium g4 to Lactobacillus genera. Conclusions: This preliminary study suggests that long-term administration of PPI may cause weight loss and changes to the microbiota in the terminal ileum.

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