• Archives of Pharmacal Research
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• v.19 no.2
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• pp.126-131
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• 1996

The effects of various synthetic benzimidazole derivatives on gastric H^+/K^+$ATPase activity in vitro were examined. The results showed that the effects of substituents on the benzimidazole ring were not significant. However, replacement of sulfoxide connecting two ring systems to sulfide resulted in a completely inactive compound in vitro, suggesting the essential role of sulfoxide group in the inhibition. In addition, compounds with 5 or 6-membered oxacyclic substituents attached to the pyridine ring displayed the most effective inhibitory activity. Among these derivatives, AU-47 was the most potent, and detailed mechanistic studies with the compound were carried out. AU-47 inhibited gastricH^+/K^+$ATPase in a concentration and time dependent manner with 50% inhibition at $6\muM$. The presence of sulfhydryl reducing agents or substrate analogue protected H^+/K^+$ATPase from the inactivation. The inhibition by AU-47 was potentiated by acid pretreatment of the compound, suggesting the structural conversion of AU-47 into a more active intermediate which was favored in acidic condition. Consistent with in vitro results, AU-47 inhibited in vivo gastric acid secretion. The results suggest that AU47 is a relevant candidate for the development of new antiulcer agent.

• Archives of Pharmacal Research
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• v.22 no.2
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• pp.137-142
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• 1999

Anti-ulcer activity of newly synthesized acylquinoline derivatives was investigated. For the in vitro screening, the effects of compounds on gastric $H^{+}/K^{+}$ ATPase isolated from hog and rabbit were examined. Among them, AU-090, AU-091, AU-254, AU-413 and AU-466 exhibited good in vitro activity on both enzymes. To correlate the in vitro activity with in vivo action, the effects of the compounds on the basal gastric acid secretion were studied. Some derivatives showed considerable anti-secretory activities, and AU-413 was selected for further studies. AU-413 protected gastric damage induced by either ethanol or NaOH dose dependently when given orally. $ED_{50}$ values of 12 mg/kg, p.o. (ethanol) and 41 mg/kg, p.o. (NaOH) were obtained. In addition, histamine-stimulated gastric secretion was reduced upon AU-413 administration. Taken together, newly synthesized acylquinoline derivatives, especially AU-413, is worthy of further investigation to be developed as an anti-ulcer agent.

• The Korean Journal of Pharmacology
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• v.23 no.2
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• pp.87-94
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• 1987

The role of central adrenergic activity in the genesis of stress ulcers was investigated by intracerebroventricular (i.c.v.) administration of catecholamines and clonidine in pylorus-ligated rats restrained for 4 hours at a temperature of $4^{\circ}C$. 1. The stress-induced ulceration was markedly decreased by the i.c.v. administration of norepinephrine, epinephrine, dopamine or low dose of clonidine. 2. After an i.c.v. administration of norepinephrine or epinephrine, the volume of gastric juice, and both acid and pepsin secretion were markedly decreased. 3. Dopamine or a low dose of clonidne decreased the volume of gastric juice and acid secretion but did not affect pepsin secretion. 4. Isoproterenol caused a decrease in the volume of gastric juice and acid secretion, however, the ulcerogenesis was similar to that of the control. 5. Gastric function as well as ulcerogenesis was little affected by a high dose of clonidine. From the above results, it is suggested that central adrenergic activation inhibits cold-restraint induced ulcerogenesis via adrenergic alpha and dopaminergic receptors, and that this effect may be mediated by a decrease in gastric acid secretion. It is also suggested that other factors may be involved in this antiulcerogenic effect.

• Biomolecules & Therapeutics
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• v.7 no.3
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• pp.285-291
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• 1999

DA-7101 is a new combined formulation of cefatrizine:clavulanic acid (2:1) under development as oral abtibiotics. The general pharmacological properties of DA-7101 on central nervous, cardiovascular, gas-trointestinal and other organ systems were studied by oral administration, in vivo and in vitro. DA-7101 had no marked effects all tests studied such as general behavior, hexobarbital-induced sleeping, spontaneous activity, anticonvulsion, body temperature, acetic acid-induced writhing, rotarod performance, heart rate and blood pressure in cats, isolated ileum movement, intestinal transition, gastric juice secretion and urine volume and electrolytes in rats. But exceptionally at the highest dose of 900 mg/kg, DA-7101 increased hexobarbital-induced sleeping time, caused a slight hypotension and decreased the secretion of gastric juice. These results suggest that at the estimated clinical dose DA-7101 would not bring about any serious acute adverse effects clinically.

• The Korean Journal of Pharmacology
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• v.12 no.1
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• pp.57-62
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• 1976

Using modified technique of Schmidt et al, as described previously (Korean J. Pharmacol 9 : 17, 1973), the stomach of female rats were perfused with physiological saline under urethane anesthesia. The acid-secretory response of the perfused stomach to i.v. hypertonic glucose (50%), casein hydrolysate (20%) or saline (6%) solution were studied with or without histamine or methacholine stimulation. A significant decrease of acid secretion from the rat stomach was induced by i.v. hypertonic glucose or saline solution. The histamine-stimulated acid secretion was also decreased by simultaneous administration of the hypertonic glucose or saline. However, methacholine-stimulated acid response was not affected by the hypertonic glucose. Intravenous infusion of 20% casein hydrolysate solution resulted in an increase in acid output from the stomach under histamine stimuli. These results lead to the conclusion that the inhibitory responses of acid secretion due to i.v. hypertonic glucose solution are brought through the effect of histaminergic, not cholnergic mechanism(s) in the gastric secretion.

• Korean Journal of Pharmacognosy
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• v.27 no.4
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• pp.295-300
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• 1996

In a preliminary screening of plant extracts for the antigastritic and antiulcer actions in rats, the extracts of head of Panax ginseng Radix showed positive activity in HCl ethanol-induced gastric lesion. Among the systematic fractions of hexane, chloroform, butanol and water, the most potent butanol fraction reduced significantly HCl ethanol-induced gastric lesion at the oral dose of 500 mg/kg. In pylorus ligated rats, hexane and butanol fraction showed decreases in the volume of gastric secretion and acid output, of which effects were stronger in butanol fraction. Further assays with butanol fraction disclosed that it significantly suppressed the aspirin-induced and Shay ulcer. The butanol fraction at the intraduodenal dose of 500 mg/kg showed significant stimulation of mucus secretion.

• YAKHAK HOEJI
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• v.35 no.5
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• pp.368-371
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• 1991

For the development of new antiulcer agents 5, 6-dihydroimidazo[2, 1-b]- thiazoles substituted at the 3-position are sythesized. Thus, the reaction of 3-chloromethyl-5, 6-dihydroimidazo[2, 1-b]thiazole(2) with thiourea and subsequently with 3-chloro-propionitrile gives 3-[3-[5, 6-dihydroimidazo[2, 1-b]thiazolyl]methylthio]propionitrile(4), which by partial alcoholysis with methanol is converted into methyl-3-[3-[5, 6-dihydro-imidazo[2, 1-b]thiazoyl]methylthio]propionimidate(5) . This compound(5) is treated finally with sulfamide or sulfonamides. 3-[3-[5, 6-dihydroimidazo[2, 1-b]thiazoyl]methylthiol-N$^{2}$-sulfamoyl-propionamidine(6) inhibited gastric acid secretion (45%) when administered intraduodenally (100 mg/kg) to pylorus-ligated rats.

• Biomolecules & Therapeutics
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• v.17 no.2
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• pp.199-204
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• 2009

In this study we investigated the protective effects of rutin, a natural plant flavonoid, on HCl/ethanol-induced gastric lesions in rats. Rutin showed the antioxidant activities, the acid-neutralizing capacities, and the inhibitory effects on the growth of Helicobacter pylori (H. pylori.), which are equivalent to control compounds. In addition, rutin significantly inhibited HCl/ethanol-induced gastric lesions. Antigastritic action of rutin may be associated with the antioxidant activities, acid-neutralizing capacities, anti-H. pylori action, and the stimulation of mucus secretion. From these results, we could suggest that rutin may be useful for the treatment and/or protection of gastritis.

• The Journal of Internal Korean Medicine
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• v.18 no.1
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• pp.1-14
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• 1997

An experimental study was done to investigate the spontaneous movements to the isolated ileum with liquid extracts of Samchulgunbitang. Then the action of gastric ulcer, gastric-juice secretion, the free acidity, total acidity, pepsin output, the transport ability in the intestine, analgesic effect and sleeping time were measured. The following results were obtained; 1. As to the spontaneous movements in the isolated ileum, the effect of contraction against suppression was recognized. 2. The effects of contraction against suppression induced by acetylcholine chloride and barium chloride were recognized on the gastric funds strip significantly. 3. The preventive effect of Samchulgunbitang on the pylorus-lightedulcer in rat was recognized significantly. 4. The anti-ulcer effect of Samchulgunbitang was not recognized on the gastric ulcer caused by indomethacin. 5. The effects of decreasing on the secretion gastric juice, the free acidity, total acidity and pepsin output of Samchulgunbitang were recognized significantly. 6. The transport rate in the small intestine of Samchulgunbitang was decreased. 7. The transport rate in the large intestine of Samchulgunbitang was increased. 8. The analgesic effect of Samchulgunbitang caused by acetic acid was recognized significantly. 9. The sleeping time caused by pentobarbital-Na of Samchulgunbitang was prolonged significantly. According to the results, it is considered that the Samchulgunbitang has effects of gastric ulcer, chronic gastritis, hyper-acidity, gastroptosis such as abdominal discomfort, gastric acid, indigestion and anorexia.

• Korean Journal of Pharmacognosy
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• v.33 no.4 s.131
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• pp.389-394
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• 2002

Present study was carried out for development of a new supplementary product with gastroprotective effect. Natural Products mentioned that have GI protective property in Dongeuibogam and reports were evaluated anti-bacterial activity against Helicobacter pylori, then five heres were selected. The material used for the test were water extract of Alpinia oxyphlla (AO), Astragalus membranaceus (AM), Cinnamomum loureirii(CL), Citrus aurantium(CA), Amomum villosum(AV). They were tested individually on HCI ethanol-induced gastric lesion in rats, AV CL, AO showed the most significant effectiveness, respectively. Then two mixture different in their content ratio (P020701-1,-2) and complex with P020701-1 (CP) were made, and tested on HCI·ethanol, indomethacin-induced gastric lesion, aspirin-ligature, Shay ulcer and gastric secretion. P020701-1, -2 and CP showed significant effect on HCI ethanol, indomethacin-induced gastric lesion, and Shay ulcer. It can be regarded that the antigasuitic and anti-ulcerative effects of P020701- 1, -2 and CP are originated from reduction of total acid output identified by gastric secretion test.