• Journal of Life Science
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• v.26 no.10
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• pp.1214-1217
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• 2016

Rebamipide is a mucosal-protective antiulcer drug, but its mechanism of action in gastric cancer remains elusive. CagA, a major virulence factor of Helicobacter pylori (H. pylori), is associated with the risk of gastric cancer. CagA protein is injected into gastric epithelial cells and deregulates a variety of cellular signaling molecules. CagA from H. pylori induces phospholipase D1 (PLD1) expression through NFκB activation in gastric epithelial cells, followed by invasion and proliferation of gastric epithelial cancer cells. Infection with cagA-positive H. pylori and expression of CagA enhances the binding of NFκB to the PLD1 promoter. Rebamipide abolishes H. pylori cagA-induced PLD1 expression via inhibition of binding of NFκB to the PLD1 promoter and also inhibits PLD activity. Moreover, rebamipide abolishes H. pylori CagA-induced β-catenin and the expression of a target cancer stem cell (CSC) marker gene via upregulation of miRNA-320a and -4496, followed by attenuation of self-renewal capacity of H. pylori CagA-infected gastric CSCs. In addition, rebamipide increases the chemosensitivity of CagA-expressed gastric CSCs and suppresses gastric carcinogenesis. Thus, it is speculated that rebamipide might show a potent efficacy as chemotherapeutic drug against gastric cancer cells. In this review, we summarizes recent results regarding the novel insights for the efficacy of rebamipide in gastric cancer cells.

• Journal of Ginseng Research
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• v.22 no.1
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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.

• Korea Journal of Hospital Management
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• v.8 no.2
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• pp.93-110
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• 2003

Fiscal crisis in the medical insurance has put the pressure upon hospitals by increasing the rate of curtailment, since the implementation of the separation between prescription and dispensing of Drug. The purpose of this study is to analyze the curtailment for antibiotics, injected drug and other drugs expenditure before and after the system of separation between prescribing and dispensing. Data were gathered from 13 general hospitals and used for analysis of trends on antibiotics and injected drug expenditure, and curtailment in 2000-2001 at three months intervals. The results were as follows; The curtailment rate of antibiotics expenditure has been increased in outpatient and inpatient since 2000. The curtailed antibiotics cost and injected drug cost in outpatient under the prescription within the hospital and in inpatient increased. The ratios of curtailment versus expenditure had increased in antibiotics, injected drugs, anticancer drugs, antiulcer drugs, albumine, antiinflammatory drugs. These results suggest that claim review system in social health insurance were over-focused mainly to control the cost and it might to impede the validity of claim review function in health insurance system. Therefore, it's needed to develope the scientific and reasonable parameter & criteria for claim review of drug expenditure.

• Korean Journal of Pharmacognosy
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• v.43 no.1
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• pp.72-78
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• 2012

Alnus japonica Steud (A. japonica) have long been used in the traditional medicine for gastric disorder, hepatitis and fatty liver in Korea. Antiulcer effects of A. japonica hot water extract (AJ ext) were evaluated by in vitro antibacterial activity against H. pylori, by the inhibitory action against the in vitro gastric $H^+/K^+$-ATPase and using rat models of gastric mucosal damage and gastric ulcer induced by HCl-ethanol, indomethacin, and restraint and water-immersion stress. For the determination of antibacterial activity of AJ ext against H. pylori, the activity of urease which released from H. pylori was measured in culture. AJ ext showed weak antibacterial activity against H. pylori with the growth inhibitions of 37% and 61% by adding final concentrations of 500 and $1000{\mu}g/ml$ culture, respectively at 24 h. To observe the inhibitory activity of AJ ext against the $H^+/K^+$-ATPase in hog gastric membrane vesicle, $IC_{50}$ value of AJ ext was $806.3{\mu}g/ml$. Pretreatment of AJ ext (200, 500 mg/kg, p.o.) prevented in a dose-dependent manner the acute gastritis in HCl-ethanol model and the formation of gastric ulcer in indomethacin model and restraint and water-immersion stress model. These results suggest that the AJ ext can be used for prevention and treatment of gastric mucosal damage and ulcers induced by various stress.

• YAKHAK HOEJI
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• v.38 no.5
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• pp.496-503
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• 1994

The combined products of antacids(AM) composed of aluminium hydroxide, magnesium hydroxide, and simethicone with a ratio of 1 : 1 : 0.1 and aceglutamide aluminium(AGA) were assayed for the antiulcer activity. The effect of the antacids(AM) in concurrent treatment with AGA was studied in acute gastric lesion induced by Shay's method, stress, ethanol, and indomethacin, in chronic gastric ulcers induced by acetic acid, and in duodenal ulcer induced by mepirizole. In all experimental models, the combined treatment of AM and AGA in the ratio of 2.3:1 showed significant potentiation in inhibition against acute gastric and duodenal ulcer and revealed a significant potentiation of the healing of chronic gastric ulcer.

• Journal of Ginseng Research
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• v.43 no.4
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• pp.550-561
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• 2019

Background: Gastric ulcer (GU) is a common gastrointestinal disease that can be induced by many factors. Finding an effective treatment method that contains fewer side effects is important. 20 (S)-ginsenoside Rg3 is a kind of protopanaxadiol and has shown superior antiinflammatory and antioxidant effects in many studies, especially cancer studies. In this study, we examined the treatment efficacy of 20 (S)-ginsenoside Rg3 on GU. Methods: Three kinds of GU models, including an alcohol GU model, a pylorus-ligated GU model, and an acetic acid GU model, were used. Mouse endothelin-1 (ET-1) and nitric oxide (NO) levels in blood and epidermal growth factor (EGF), superoxide dismutase, and NO levels in gastric mucosa were evaluated. Hematoxylin and eosin staining of gastric mucosa and immunohistochemical staining of ET-1, inducible nitric oxide synthase (NOS2), and epidermal growth factor receptors were studied. Ulcer index (UI) scores and UI ratios were also analyzed to demonstrate the GU conditions in different groups. Furthermore, Glide XP from $Schr{\ddot{o}}dinger$ was used for molecular docking to clarify the interactions between 20 (S)-ginsenoside Rg3 and EGF and NOS2. Results: 20 (S)-ginsenoside Rg3 significantly decreased the UI scores and UI ratios in all the three GU models, and it demonstrated antiulcer effects by decreasing the ET-1 and NOS2 levels and increasing the NO, superoxide dismutase, EGF, and epidermal growth factor receptor levels. In addition, high-dose 20 (S)-ginsenoside Rg3 showed satisfactory gastric mucosa protection effects. Conclusion: 20 (S)-ginsenoside Rg3 can inhibit the formation of GU and may be a potential therapeutic agent for GU.

• 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.

• Biomolecules & Therapeutics
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• v.6 no.1
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• pp.37-44
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• 1998

This study was performed to examine the effects of DA-9601, a novel antiulcer agent extracted from Artemisiae Herba, on radiation colitis in the rat. Female Wistar rats received a 30 Gy dose of irradiation to the 2 cm of distal colon in length using an intrarectal applicator system. 30 mg/tg or 100 mg/kg of DA- 9601 was administered orally 30 min before and 4 h after radiation on day 1. And the same dose of DA-9601 was given to the animals twice a day from day 2 to 14. As a reference control, sucralfate suspension (100 or 300 mg/head) was given as an enema based on the same treatment schedule of DA-9601. Body weight change and the frequency of diarrhea were recorded during the observation period as markers of radiationinduced injury, All animals were sacrificed on day 15 for evaluation of macro- and microscopic findings and mucosal myeloperoxidase (MPO) activity. Radiated animals showed diarrhea, mucosal redness and histologic changes characterized by edema and eosinophilic infiltration of the periglandular lamina propria with loss of colonic epithelium. Radiation also significantly increased mucosal MfO activity of affected colon f\\\\\\\\`<0.05). However, most of these changes were completely protected by oral administration with DA-9601. DA-9601 reduced radiation-induced histologic alteration significantly in a dose-related manner (P<0.05). In addition, mucosal MPO activity in rats receiving high dose of DA-9601 decreased significantly when compared with that in radiated control. High dose of sucralfate (300 mg/head) alleviated radiation-induced histologic lesion, but failed to reach statistical significance. The results of this study suggest that DA-9601 can be useful for the prevention of acute clinical symptoms of radiation proctocolitis and that decrease of mucosal MPO by DA-9601 plays a role in its protective mechanism(s), at least in part.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.9
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• pp.1027-1034
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• 2017

The immune system is a complex process within the body that protects against disease. Recently, many studies have attempted to discover immunomodulative compounds from natural sources. Pinus koraiensis (PK) cone shell is a by-product of PK. One of the major compounds of PK cone shell is dehydroabietic acid, which has bioactivity, including antiulcer and anti-inflammatory activities. Therefore, this study was performed to examine the immunomodulative effects of PK cone shell. The immunomodulatory effects of PK cone shell extracted with 20% ethanol (EtOH) in vivo were examined initially by measuring the natural killer (NK) cell activity, phagocytic activity, Th1/Th2 cytokines release, serum immunoglobulin, and T/B cell proliferation. The NK cell activity and phagocytic activity were increased significantly by a treatment with a 20% EtOH extract of PK cone shell. Th1 type cytokine and T cell proliferation increased and Th2 type cytokine, B cell proliferation and serum immunoglobulin A, G, and E decreased after a treatment with PK cone shell extract. The 20% EtOH extract of the PK cone shell normalized the unbalanced production of Th1/Th2 type cytokine. This suggests that a 20% EtOH extract of PK cone shell has great potential as a health food.

• The Journal of Korean Medicine
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• v.19 no.1
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• pp.179-204
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• 1998

The purpose of this research was to investigate the efficacy of Goiwhasan extract powder on the gastric injuries, antiulcer, gastrointestinal tract and blood hemostasis. Animals were used through this studies mice and rats. All animals were divided into 3 groups, contol group(no treatment), sample Ⅰ group(375mg/kg administration), sample Ⅱ group(750mg/kg administration). The gastric injuries and ulcer have been made by using pyloric ligation, indomethacin, HCI-ethanol, acetic acid and then The histological observation was followed. In the gastrointestinal tract, gastric juice secretion, gastric acidity, pepsin output, blood gastrin and secretin level, transport potentials in the small and large intestine were checked. And studies on blood hemostasis were performed on normal hemostatic activities and plasma prothrombin time, plasma recalcification time, plasma fibrinogen levels in the hypoprothrombinemic mice induced by warfarin. The results were as follows: 1. The antigastric ulcer effects on the pyloric ligation, indomethacin, HCl-ethanol, acetic acid induced gastric injuries were shown in Sample Ⅱ group(p<0.05). 2. Through the morphologic examination on the acetic acid induced ulcer, Sample Ⅰ group showed mild regeneration of epithelium and slight decrease of periulcer edema then that of Control group, while Sample Ⅱ group showed more retraction of round ulcer site, remarkable loss of swelling and edema then that of Control group, and revealing the regenerated epithelium in the surrounding ulcer site. Thus it was noted that both Sample groups have antigastriculcer effects on the experimentally induced gastric ulcer. 3. The inhibitory effects on gastric juice were noted in both Sample Ⅰ group(p<0.05) and Sample Ⅱ group(p<0.01). However, only Sample Ⅱ group showed the inhibitory effects on total acidity and pepsin output(p<0.05). 4. The significant inhibition of blood gastrin level showed at 30 min.(P<0.05) and 90 min.(P<0.05) after starting medication in only Sample Ⅱ group, but significance of blood secretin level in both groups was not recognized. 5. Any significant changes in barium sulfate transport in the small intestine of mice was not recognized in both groups, but the significantly inhibitory effect in large intestine was recognized in both Sample Ⅰ group(p<0.05) and Sample Ⅱ group(p<0.001). 6. In hemostatic effect on both normal mice and hypoprothrombinemic mice induced by warfarin, the significantly shortening effect on coagulation time was seen in only Sample Ⅱ group(p<0.01). 7. On plasma prothrombin time in hypoprothrombinemic rat induced by warfarin, Sample Ⅱ group have shortened the prothrombin time significantly(p<0.001). 8. On plasma reclcification time in hypoprothrombinemic rat induced by warfarin, the recalcification time have been shortened significantly in both Sample Ⅰ group(p<0.05) and Sample Ⅱ group(p<0.01). 9. On plasma fibrinogen levels in hypoprothrombinemic rat induced by warfarin, the fibrinogen contents in Sample Ⅱ have been decreased significantly(p<0.01). Overall the above results suggest that Goiwhasan has an therapeutic efficacy on antigastric ulcer and blood hemostasis. Further studies would be needed on the interaction of its herbal medicine and its mechanism in the future.