• Archives of Pharmacal Research
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• 제21권3호
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• pp.241-247
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• 1998

This study was designed to determine biochemical and pharmacological properties of a newly synthesized benzimidazole derivative, 2-amino-4, 5-dihydropyrido [1, 2-a] thiazolo [5, 4-g] benzimidazole (YJA20379-5) in vitro and in vivo. In the leaky membrane vesicles of pig gastric mucosa, YJA20379-5 inhibited the $K^+$-stimulated $H^+$, $K^+$-ATPase activity in a concentration- and time-dependent manner, with $IC_{50}$ values being $43{\mu}\textrm{M}$ and $43{\mu}\textrm{M}$ at pH 6.4 and 7.4, respectively. YJA20379-5, given intraduodenally, had a potent inhibitory effect on the gastric acid secretion in pylorus-ligated rats. The $ED_{50}$ value for acid secretion was 15.4 mg/kg. YJA20379-5, administered orally, also suppressed gastric damages induced by water-immersion stress, indomethacin and ethanol, and duodenal damage induced by mepirizole in rats; the $ED_{50}$ values were 17.6, 4.7, 3.0 and 18.7 mg/kg, respectively. Furthermore, repeated oral administration of YJA20379-5 accelerated the spontaneous healing of acetic acid-induced gastric ulcers in rats. It is concluded that the a-ntisecretory activity of YJA20379-5 appears to be associated with inhibition of $H^+$, $K^+$-ATPase, while its antigastric and antiduodenal lesion activities are primarily related to the antisecretory effect.

• Journal of Gastric Cancer
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• 제1권1호
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• pp.4-9
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• 2001

Purpose: The trefoil factor family 1 (TFF1) has a protective effect against gastric mucosal damage induced by nonsteroidal anti-inflammatory drugs or ethanol. In addition, a TFF1 knockout mouse model has exhibited circumferential adenomas with high-grade dysplasia, of which $30\%$ progressed into frankly invasive carcinomas. We tried to determine whether the expression pattern of the TFF1 could be involved in the development of sporadic gastric carcinomas. Materials and Methods: We examined TFF1 expression in a series of 43 sporadic gastric carcinomas and 18 gastric adenomas by immunohistochemistry. Results: Strong positive TFF1 staining was identified primarily in the normal gastric mucosa, mainly in the cytoplasm of the superficial and foveolar epithelium. We found TFF1 expression in $55.8\%$ (24 out of 43) of the gastric carcinomas and in $16.7\%$ (3 out of 18) of the gastric adenomas. Statistically, TFF1 immunoreactivity was significantly higher in diffuse-type ($82.4\%$) than in intestinal-type ($38.5\%$) carcinomas(p=0.0058, Fisher's exact test). Conclusion: Our findings provide sufficient evidence that the expression of TFF1 in gastric cancer may simply disclose gastric-type differentiation of neoplastic cells and provide further support for the existence of at least two pathways of malignant transformation of the gastric mucosa: one via intestinal metaplasia and adenomatous dysplasia, leading to glandular carcinomas with intestinal-type differentiation, and the other via hyperplastic changes or de novo changes, leading to diffuse carcinomas and to a subset of glandular carcinomas displaying gastric-type differentiation.

• 한국식품위생안전성학회지
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• 제31권4호
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• pp.286-293
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• 2016

본 연구에서는 ursolic acid의 위의 보호효과를 위한 실험을 실시하였다. 위장 질병에 대한 ursolic acid의 효과를 확인하기 위해서 급성, 만성위염은 각각의 HCl ethanol과 indomethacin에 의해 유도된 위염 동물 모델을 사용하여 관찰하였다. 대표적인 공격인자인 위산에 관해서는 PPI activity를 통해서 확인하였고, 위의 손상에 대한 보호인자에 관해서는, $PGE_2$를 정량적으로 분석하였다. 항균활성 실험은 만성위염, 위궤양, 위암에 원인인자로 잘 알려진 H. pylori로 실험하였다. AGS cell를 이용하여 DAPI 염색, Flow cytometry assay를 통하여 ursolic acid가 위암세포의 apoptosis에 관여하는지를 확인하였다. 그 결과 ursolic acid는 HCl ethanol과 indomethacin에 의해 유도된 급성, 만성에 대한 위손상을 억제하였다. Ursolic acid는 위산분비의 마지막 단계인 위염분비효소인 proton pump를 억제시킴으로써 산의 분비를 억제하였다. 그리고 ursolic acid는 위 점막의 보호인자인 $PGE_2$의 농도가 증가함으로써 위 점막 보호 효과를 확인하였다. 또한 ursolic acid는 공격인자인 H. pylori colonization을 억제하였다. DAPI를 이용한 핵 염색에서, 대조군과는 달리, 핵 형상의 변형과 함께 수축 된 세포 또는 염색질의 응축현상이 관찰되었다. Flow cytometry assay에서 ursolic acid에 의해 apoptosis가 증가하는 것을 확인 하였다. 이를 통하여 ursolic acid는 위 손상에 대한 방어 효과가 있음을 확인할 수 있었다.

• The Korean Journal of Physiology and Pharmacology
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• 제5권3호
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• pp.279-285
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• 2001

Although only a minority of the infected individuals develops atrophic gastritis and the malignancy, factors governing clinical outcomes subsequent to Helicobacter pylori (H. pylori) infection have not yet been defined. H. pylori infection is characterized by extensive infiltration of neutrophils. Myeloperoxidase (MPO) in neutrophils amplifies the oxidative potential of hydrogen peroxides that induce gastric mucosal damage, thus MPO is suspected to play a role in H. pylori-induced gastric injury. Therefore, we explored the association of host MPO genetic polymorphism with atrophic gastritis upon H. pylori infection. Biopsy specimens taken from the gastric mucosa were examined histologically in 87 patients. The PCR-RFLP assay was used to characterize MPO genotypes. The distributions of MPO genotypes were MPO (G/G) 82% and MPO (G/A) 18%. None of MPO (A/A) genotype was observed. A strong positive correlation between the levels of neutrophil infiltration and gastric atrophy found only in MPO (G/G) but not in MPO (G/A) genotype. These results suggest that MPO genotype is a critical determinant in the pathogenesis of atrophic gastritis subsequent to H. pylori infection. Further works need to clarify the functional relevance of MPO genetic polymorphisms on gastric cell injury.

• The Korean Journal of Physiology and Pharmacology
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• 제25권4호
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• pp.261-272
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• 2021

Doxorubicin (Dox) is widely used to the treatment of cancer, however, it could cause damage to gastric mucosa. To investigate the protective effects and related mechanisms of coenzyme Q10 (CoQ10) and vitamin C (VC) on Dox-induced gastric mucosal injury, we presented the survey of the 4 groups of the rats with different conditions. The results showed Dox treatment significantly induced GES-1 apoptosis, but preconditioning in GES-1 cells with VC or CoQ10 significantly inhibited the Dox-induced decrease and other harm effects, including the expression and of IκKβ, IκBα, NF-κB/p65 and tumor necrosis factor (TNF-α) in GES-1 cells. Moreover, high-throughput sequencing results showed Dox treatment increased the number of harmful gut microbes, and CoQ10 and VC treatment inhibited this effect. CoQ10 and VC treatment inhibits Dox-induced gastric mucosal injury by inhibiting the activation of the IkKB/IκBα/NF-κB/p65/TNF-α pathway, promoting anti-inflammatory effects of gastric tissue and regulating the composition of the intestinal flora.

• Journal of Acupuncture Research
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• 제30권2호
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• pp.31-41
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• 2013

Objectives : This study was to evaluate inhibitory effects of Naegwan-acupuncture($PC_6$) on acute RE(reflux esophigitis) rat induced by pylorus and forestomach ligation operation. Methods : Twenty seven SD rats were divided three groups (intact normal rat; RE control rat; RE control rat respectively stimulated by Naegwan point($PC_6$)). All rats was fasted for 18 h but free water, we induced RE by pylorus and forestomach ligation operation. Six hour after the operation, rats were sacrified, collected bloods in the abdominal vein, dissected a esophagus and stomach. The stomach was washed a 1 ml PBS to research gastric volume, pH, acidity and mucin release of gastric juice, esophagus was cut longitudinally and pictured a innter mucosa area to research damages in esophagus. The proinflammatory cytokine and chemokine including IFN-${\gamma}$, TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and MCP-1 were analyzed by ELISA kit. Results : 1. Significantly, death rate of $PC_6$ acupuncture rat group was decreased compared to that of RE control group. 2. Gastric Volume, gastric injury and esophageal mucosa demage were decreased significantly, too. 3. Compared with RE, all of the proinflammatory cytokine and chemokine analyzed in serum of $PC_6$ were decreased remarkably. Especially, there were significant meanings TNF-${\alpha}$, IL-6 and MCP-1 in serum of $PC_6$ were decreased. Conclusion : The results suggest that antiinflammatory and protecting effects of PC6 could attenuate the severity of reflux esophagitis and prevent the esophageal mucosal damage, and validate its therapeutic use in esophageal reflux disease.

• 대한한방내과학회지
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• 제43권4호
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• pp.738-750
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• 2022

Objective: Alcohol is known to cause inflammation in the stomach by decreasing the protective substances of the gastric mucosa and increasing oxidative stress. The purpose of this study was to investigate the anti-inflammatory effect of Artemisiae Argyi Folium extract (AF) on alcohol-induced gastritis. Methods: The total polyphenol and flavonoid contents of AF were confirmed through an in vitro experiment. Radical scavenging activities were confirmed using DPPH and ABTS assays. In vivo experiments were conducted on mice divided into 5 groups (n=8): a normal group (Nor), an alcohol-induced gastritis group (Con), an alcohol-induced gastritis group administered 10 mg/kg sucralfate (SC), an alcohol-induced gastritis group administered 100 mg/kg AF (AFL), and an alcohol-induced gastritis group administered 200 mg/kg AF(AFH). The serum levels of reactive oxygen species (ROS) were determined, and protein expressions were confirmed in gastric tissues. Results: In alcohol-induced gastritis, AF alleviated damage to the gastric mucosa caused by alcohol. AF also decreased the serum ROS levels. Western blots showed that AF decreased the expression of NADPH oxidase and decreased the expression of the NF-κB pathway associated with inflammation. AF also decreased the expression of adhesion molecules and chemokine proteins, and increased the expression of anti-inflammatory proteins. Conclusions: AF not only reduced oxidative stress in alcohol-induced gastritis, but it also relieved gastric mucosal inflammation by regulating the expression of the NF-κB pathway.

• 생약학회지
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• 제53권3호
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• pp.153-161
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• 2022

Cotoneaster mongolicus Pojark. (CM), in the family Rosaceae is an endemic plant to the Mongolian region (its name: Moнroл чapraй). In Mongolia, Cotoneaster species as a crude drug is mainly used for inflammatory diseases, diarrhea, and stomach indigestion. In this study, we evaluated the gastro-protective activity underlying mechanism of CM. For in vivo experiments, mice were divided into 5 groups; normal mice (Normal), gastritis mice (Control), gastritis mice treated with sucralfate 10 mg/kg (SC), gastritis mice treated with CM 100 mg/kg (CML), gastritis mice treated with CM 200 mg/kg (CMH). Gastritis was provoked by HCl/ethanol (60% ethanol in 150 mM HCl). After oral administration of each drug, HCl/ethanol was orally administered 90 mins later to induce gastritis. CM alleviated the damage to the gastric mucosa caused. As a result of confirming the expression of protein in gastric tissue through western blot, CM significantly reduced the expression of NF-κB activated due to gastritis. Also, it significantly modulated the Nrf2-Keap1 pathway. These results indicate that CM not only inhibits the nuclear metastasis of NF-𝛋B but also modulates the Nrf2-Keap1 pathway to relieve inflammation of the gastric mucosa.

• 대한임상검사과학회지
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• 제55권4호
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• pp.291-297
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• 2023

위염과 위궤양은 위 점막에 염증이 생기고 상처가 생기는 것을 말한다. 과거 연구는 주로 환경적 요인이 위 질환의 주요 요인이라는 관점에서 이루어졌으나, 최근 유전자 연구의 발전으로 유전적 요인의 중요성이 강조되고 있다. SLC25A26은 활성산 소종의 축적과 관련이 있는 유전자이다. 산화 스트레스는 염증반응을 촉진하여 활성 산소를 증가시키고 세포 손상을 유발하기 때문에 이는 위 질환의 발생과 관련이 있을 것이라 추정된다. 본 연구에서는 SLC25A26과 위 질환과의 연관성을 분석하였다. 국내 위 질환 환자 1,369명과 건강한 대조군 7,471명을 대상으로 SLC25A26 내 다형성을 분석하였다. 그 결과 11개의 단일 염기 다형성(single nucleotide polymorphism, SNP) (genotype)과 13개의 SNP (imputation)가 통계적인 유의성(P<0.05)을 가지고 높은 위 질환과의 상대 위험도를 보였다. 그 중 SLC25A26의 rs13874가 위 질환과 높은 연관성을 보였다. 유전자형 기반 mRNA 발현 분석에 따르면 SLC25A26이 minor allele를 가지면 mRNA 발현이 증가하고 이는 산화 스트레스를 증가시킬 가능성이 있다. 결론적으로 SLC25A26 다형성은 위질환과 관련이 있어 우리나라 인구에서 위 질환 관리의 새로운 지침에 대한 근거를 제공할 수 있을 것이다.

• 대한본초학회지
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• 제37권5호
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• pp.63-74
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• 2022

Objective : Gastritis refers to an inflammatory disease of the gastric mucosa. Alcohol is one of the main aggression factors, causing bleeding and inflammation in the gastric mucosa and it is known to not only increase lipid peroxide levels, but also deplete key antioxidant factors. The purpose of this study was to determine the effect of Uncariae Ramulus et Uncus water extract (URW) in alcohol-induced gastritis. Methods : The total polyphenol and flavonoid contents of URW were confirmed through an in vitro experiment. Also, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity and ferric reducing antioxidant power (FRAP) activity were confirmed. For in vivo experiments, mice were divided into 4 groups (n=8). Also, 1 hr after oral administration of each drug, 50% ethanol was orally administered to induce gastritis. Results : As a result of in vitro experiments, URW showed excellent antioxidant activity. In alcohol-induced gastritis, URW alleviated the damage to the gastric mucosa caused by alcohol. Also, URW decreased reactive oxygen species (ROS) and malondialdehyde (MDA) levels in serum and gastric tissues, and significantly decreased the expression of NADPH oxidases in gastric tissues. In addition, it significantly modulated the nuclear factor erythroid-derived 2-related factor 2 (Nrf2) and nuclear factor-𝜅B p65 (NF-𝜅B) pathways as well as significantly increased the expression of anti-inflammatory proteins. Conclusions : These results suggest that URW not only reduces oxidative stress through excellent antioxidant activity but also relieves gastric mucosal inflammation as a regulator of Nrf2 and NF-𝜅B pathways.