• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.6
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• pp.996-1003
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• 2010

This study was performed to investigate the effect of promoting gastrointestinal function and inhibiting of decreasing body temperature of ginger extract(Zingiber officinale) in rats. In order to elucidate the gastrointestinal function and inhibiting effect of body temperature of native ginger and improved ginger, water extracts of ginger were orally administrated into rats. The results are as follows: The gastrointestinal transit time was significantly decreased in native ginger(7.66hrs) and improved ginger(7.72hrs) extract administrated groups compare to control group(8.44hrs). The mean red faecal weight was increased in native ginger(30.6%) and improved ginger(31.1%) extract administrated groups compare to control group(24.9%) for 24hrs. Inhibiting effect of decreasing body temperature induced by serotonin was increased in native ginger($1.116^{\circ}C$) and improved ginger($1.416^{\circ}C$) extract administrated groups compare to positive control group($0.384^{\circ}C$) during 40 minutes. Gastrin and CGRP immunoreactive density was more strongly expressed in native ginger and improved ginger extract administrated groups compare to control group. Serotonin immunoreactive density was more weakly expressed in native ginger and improved ginger extract administrated groups compare to control group. These results suggest that ginger extracts may enhance physiological activity such as gastrointestinal motility, protection of mucosa and gastric acid secretion in gastrointestinal tracts, and inhibits decreasing body temperature

• Biomolecules & Therapeutics
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• v.5 no.4
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• pp.369-375
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• 1997

General pharmacological effects of SB-31$^{R}$, the extracts of Pulsatilla koreana, were investigated in mice, rats and guinea-pigs. Intravenous injection of SB-31 (3 and 6 ml/kg) produced almost no effect on central nervous system no effects on the general symptom and behaviors of mice, spontaneous locomotor activity, pentobarbital- induced sleeping time , rotared performance , electroshock and pentylenetertrazole -induced seizures, acetic acid-induced writhing and normal body temperature in mice. SB-31 showed little effects on the spontaneous movement of the isolated ileum and contraction induced by agonists in isolated ileum, suggesting no influence on autonomic nervous system. Administration of SB-31 also did not show any effect on blood pressure in conscious rats. However, a slight decrease in heart rate was observed at high doses (6 and 10 ml/kg) of SB-31 in conscious rats. Similarly, a slight increase in respiratory rate was observed at 6 m1/kg of SB-31 in anesthetized rats. SB-31 did not produce any effect at the dose of 3 ml/kg, but showed a tendency to increase the urinary volume at 6 ml/kg, and produced a decrease in urinary excretions of N $a_{+}$and $K_{+}$at 6 ml/kg. However, transport capacity within the gastrointestinal tract and the secretion of the gastric juice were not influenced by 6 ml/kg of SB-31. In conclusion, these results suggest that SB-31 did not pro-duce any acute effects on the central nervous system, autonomic nervous system, respiratory and circulatory systems, digestive system and kidney function at the dose of below 3 ml/kg.ml/kg.

• Biomolecules & Therapeutics
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• v.7 no.3
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• pp.271-277
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• 1999

Safety evaluation of LB71350, a new HIV-1 protease inhibitor, was performed in mice, rats and dogs. For the general behavior of mice, LB71350 at an oral dose of 200 mg/kg did not show any significant effects on muscle tone and locomotor activity. In terms of central nervous system, at oral doses of 200 mg/kg and 1000 mg/kg, LB71350 inhibited acetic acid-induced pain response approximately 41% and 83% of control. respectively. At oral doses of 200 mg/kg and 500 mg/kg, it reduced the rectal body temperature in rats. Pentylenetetrazole-induced seizure in mice was slightly potentiated by oral administration of LB71350 at doses ranging from 200 mg/kg to 1000 mg/Ag. Single or five day treatment of LB71350 doubled the hexobarbital- induced sleeping time in mice at oral doses ranging from 50 mg/kg to 500 mg/kg. It did not cause any effects on gastric secretion and acidity in rat at oral doses of 200 mg/kg and 1000 mg/kg and also it did not change intestinal motility in mice up to 1000 mg/kg. Blood coagulation indices such as prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time (TT) in rats were not affected by the treatment of LB71350 up to 500 mg/kg. LB71350 caused no significant effects on the cardiac output, stroke volume, heart rate, and mean blood pressure when infused intravenously to the anesthetized rats and dogs. Taken together, LB71350 at high oral doses caused significant pharmacological effects on the central nervous system and the hexobarbital-induced sleeping time.

• YAKHAK HOEJI
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• v.50 no.6
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• pp.386-392
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• 2006

Pramlintide, a synthetic analogue of human hormone amylin, is the first of a new class of amylinomimetic compounds. Present study was undertaken to compile and analyze the clinical trials of pramlintide, and thereby to facilitate the design of the bridging study for the earlier introduction of the drug, which might be needed by diabetes patients in Korea. Sixty-two articles from Pubmed and MEDLINE search were used to analyze the trials of pramlintide along with prescribing information and New Drug Application packet obtained form the manufacturer. The efficacy of the new drug was attributed to three mechanisms: delay of gastric emptying time, inhibition of post-prandial glucagon secretion, and reduction of food intake by enhanced satiety. Clinical trials consistently identified the effectiveness of the drug for the treatment of type 1and type 2 diabetes who have failed to achieve glycemic control despite optimal therapy with insulin. However, the six pivotal Phase III clinical trials were peformed with mostly caucasian and some black and hispanic people. None of the trials documented the proportion of either Asian or Korean participants. Since Korean diabetes patients show different epidemiology and characteristics in their disease state, it appears that the bridging study of pramlintide should be designed in the level of full scale Phase III clinical trial along with pharmacokinetic and pbarmacodynamic studies.

• The Journal of Internal Korean Medicine
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• v.39 no.6
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• pp.1136-1149
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• 2018

Objectives: The aim of this study was to perform a meta analysis of randomized controlled trials (RCTs) that applied Opae-san to peptic ulcer. Methods: The databases NDSL, RISS, KISS, KISTI, Oasis, DBpia, Cochrane, EMBASE, Pubmed, and CNKI were searched to identify RCTs that evaluated the therapeutic response to Opae-san on peptic ulcer. The selected studies were assessed using Cochrane Group's risk of bias tool. Results: 12 RCTs were selected from a total of 312 identified. Combined therapies of Opae-san plus triple therapy were superior to only triple therapy in achieving the effective rate (risk ratio=1.26, 95% CI: 1.17 to 1.35, p<0.001, I2=0%), the helicobacter pylori eradication rate (risk ratio=1.23, 95% CI: 1.12 to 1.34, p<0.001, I2=7%) and the recurrence rate (risk ratio=0.31, 95% CI: 0.12 to 0.82, p=0.02, I2=0%). But only Opae-san was not superior in achieving the effective rate compared to anti gastric secretion drugs. Conclusions: The current evidence suggests that combined therapies of Opae-san plus triple therapy yield a higher effective rate, and helicobacter pylori eradication rate and a lower recurrence rate. However, in most of these studies, it is difficult to evaluate the bias and therefore better designed studies are needed.

• Biomolecules & Therapeutics
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• v.29 no.4
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• pp.410-418
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• 2021

Helicobacter pylori causes chronic gastritis through cag pathogenicity island (cagPAI), vacuolating cytotoxin A (VacA), lipopolysaccharides (LPS), and flagellin as pathogen-related molecular patterns (PAMPs), which, in combination with the pattern recognition receptors (PRRs) of host cells promotes the expression and secretion of inflammation-causing cytokines and activates innate immune responses such as inflammasomes. To identify useful compounds against H. pylori-associated gastric disorders, the effect of chalcone derivatives to activate the nucleotide-binding oligomerization domain (NOD)-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome was examined in an H. pylori-infected human monocytic THP-1 cell line in this study. Among the five synthetic structurally-related chalcone derivatives examined, 2'-hydroxy-4',6'-dimethoxychalcone (8) and 2'-hydroxy-3,4,5-trimethoxychalcone (12) strongly blocked the NLRP3 inflammasome in H. pylori-infected THP-1 cells. At 10 μM, these compounds inhibited the production of active IL-1β, IL-18, and caspase-1, and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) oligomerization, but did not affect the expression levels of NLRP3, ASC, and pro-caspase-1. The interruption of NLRP3 inflammasome activation by these compounds was found to be mediated via the inhibition of the interleukin-1 receptor-associated kinase 4 (IRAK4)/IκBα/NF-κB signaling pathway. These compounds also inhibited caspase-4 production associated with non-canonical NLRP3 inflammasome activation. These results show for the first time that certain chalcones could interrupt the activation of the NLRP3 inflammasome in H. pylori-infected THP-1 cells. Therefore, these chalcones may be helpful in alleviating H. pylori-related inflammatory disorders including chronic gastritis.

• Korean Journal of Microbiology
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• v.48 no.2
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• pp.109-115
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• 2012

Helicobacter pylori is an important factor of chronic gastritis, digestive ulcer, and stomach cancer. CagL, a virulence factor of H. pylori, is well-known as a pilus protein which acts as adhesion to host cell and a component of Type 4 secretion system. In this study, we evaluated the protective response of recombinant CagL protein (rCagL) using Mongolian gerbil animal model for H. pylori infection. The cagL gene was cloned from 26695 H. pylori followed by over-expression and purification of the protein in E. coli. Mongolian gerbils were immunized with rCagL protein mixed with aluminum adjuvant via intramuscular injections once a week during 4 weeks. At a week after the last immunization, the Mongolian gerbils were administrated with H. pylori 7.13 strain into the stomach and sacrificed to measure antibody titer on rCagL by ELISA and bacterial colonization in the stomach, and to examine the histopathological changes and cytokine expression at 6 week after challenge. Antibody titers on recombinant protein were significantly increased from a week after the first immunization. There was no significant change of the number of bacterial colony between control group and immunized group. The relative stomach weight was significantly decreased in immunized group, but the significant change of histopathological assessment was not observed in the stomach. Cytokine expression such as IL-$1{\beta}$ and KC also was not significantly different between control and immunized groups. These results indicate that rCagL could effectively induce the formation of the specific IgG antibodies. However, bacterial colonization and histopathological lesions could not be inhibited by the immunization in the stomach, indicating not enough protection against H. pylori infection. We consider that along with CagL other adequate antigens could be needed stimulating immune response and inducing protective effects against gastric disease, and also a better adjuvant could be considered.

• Journal of Food Hygiene and Safety
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• v.13 no.1
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• pp.53-61
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• 1998

This study was performed to investigate the antiulcer effects of Opuntia dillenii Haw. on the stomach ulcer induced by restraint and water-immersion stress in rats. For this experiment, 48 male Sprague-Dawley strain were used. The experimental groups were divided into four: a control (C) and 3 Opuntia dillenii Haw. treatment groups (E-1, E-2, E-3). Each dose of Opuntia dillenii Haw. was 30 mg/kg bw (E-1), 60 mgfKg bw (E-2) and 120 mg/kg bw (E-3). The rats were allocated to each group by 12 and observed for 4 weeks. The results were as following: 1. The stomach surface pH in each group showed no significant difference, but the values of Opuntia dillenii Haw. treatment groups were higher than the value of the control group. 2. The gastric wall mucus was increased in all Opuntia dillenii Haw. treatment groups compared with the control group. Especially in E-1 difference was higher (p<0.05) and in E-2 difference was significantly higher (p<0.01). 3. At shear rate 11.25, 45.0, 90.0, $225\;sec^{-1}$, whole blood viscosity and plasma viscosity were measured. Most of the values of Opuntia dillenii Haw. treatment groups were low compared with that of the control group. At shear rate 90.0, $225\;sec^{-1}$ the values of whole blood viscosity in E-1 were significantly low (p<0.05) and at shear rate 11.25, $45.0\;sec^{-1}$, more significant (p<0.01). At shear rate 11.25, 45.0, 90.0, $225\;sec^{-1}$ the values of whole blood viscosity in E-2 were significantly low (p<0.01). At shear rate $90.0\;sec^{-1}$ the value of plasma viscosity in E-1 was significantly low (p<0.05) and at shear rate 90.0, $225\;sec^{-1}$ the values of plasma viscosity in E-2 we resignificantly low (p<0.01). 4. Less severe ulcers were obsered in Opuntia dillenii Haw. treatment groups than in the control group. Especially E-1 groups tissues had only slight ulcers and necrosis of tissue was not observed in this group. From the results of this study, it can be concluded that the oral administratio-n of Opuntia dillenii Haw. results in protection of stomach ulcer by stimulating the secretion of gastric mucus and improving the gastric mucosal microcirculation.

• Applied Microscopy
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• v.6 no.1
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• pp.9-20
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• 1976

The present study was performed to clarify the histochemical compositions and fine structure of the mucus secreting cells in the gastrointestinal mucosa of normal mice. The mucus cells in the surface epithelium of stomach body had neutral mucin and some quantity of weak acid mucin. And the mucus cells in gastric pits and mucus neck cells had neutral mucin. The goblet cells in villial epithelium of small intestine contain strong acid sulfated mucin as their main content and a little of neutral mucopolysaccharide. However, the goblet cells in intestinal glands-Liberkuhn crypt were confirmed to contain non-sulfated weak acid mucin. The goblet cells in the surface epithelium of colon had the same component as the small intestine did. But the cells in the crypts of colon contained neutral and weak acid mucin as their main contents. The majority of secretory granules of the surface epithelial cells of the stomach body had high electron density, and some granules with low electron density appeared too. While the mucin granules in the mucus neck cells were low in its electron density, and some of those granules were frequently found to have dense core in them. Secretory granules in goblet cells of small and large intestines had low electron density. The mode of secretion in mucin-containing cells in gastro-intestinal tract was found to be merocrine.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.2
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• pp.89-94
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• 2014

DA-6034, a eupatilin derivative of flavonoid, has shown potent effects on the protection of gastric mucosa and induced the increases in fluid and glycoprotein secretion in human and rat corneal and conjunctival cells, suggesting that it might be considered as a drug for the treatment of dry eye. However, whether DA-6034 induces $Ca^{2+}$ signaling and its underlying mechanism in epithelial cells are not known. In the present study, we investigated the mechanism for actions of DA-6034 in $Ca^{2+}$ signaling pathways of the epithelial cells (conjunctival and corneal cells) from human donor eyes and mouse salivary gland epithelial cells. DA-6034 activated $Ca^{2+}$-activated $Cl^-$ channels (CaCCs) and increased intracellular calcium concentrations ($[Ca^{2+}]_i$) in primary cultured human conjunctival cells. DA-6034 also increased $[Ca^{2+}]_i$ in mouse salivary gland cells and human corneal epithelial cells. $[Ca^{2+}]_i$ increase of DA-6034 was dependent on the $Ca^{2+}$ entry from extracellular and $Ca^{2+}$ release from internal $Ca^{2+}$ stores. Interestingly, these effects of DA-6034 were related to ryanodine receptors (RyRs) but not phospholipase C/inositol 1,4,5-triphosphate ($IP_3$) pathway and lysosomal $Ca^{2+}$ stores. These results suggest that DA-6034 induces $Ca^{2+}$ signaling via extracellular $Ca^{2+}$ entry and RyRs-sensitive $Ca^{2+}$ release from internal $Ca^{2+}$ stores in epithelial cells.