• Biomolecules & Therapeutics
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• 제5권3호
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• pp.228-232
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• 1997

AU-164 was synthesized as a reversible gastric $H^+/K^+$ ATPase inhibitor, and its effects were tested in various systems. AU-164 inhibited rabbit gastric $H^+/K^+$ ATPase with an $IC_{50}$/ of 9 $\mu$M. On the other hand, AU-164 was a weak inhibitor for dog kidney $Na^+/K^+$ ATPasc, indicating the selectivity for gastric $H^+/K^+$ ATPase. The reversible property of the AU-164-induced inhibition of $H^+/K^+$ ATPase was confirmed by filtering the inhibition mixture through Sephadex G-25M column. In vivo basal acid secretion was also inhibited by AU-164 under the pylorus ligation of Sprague-Dawley rats. In addition, AU-164 protected dose dependently gastric lesion induced by ethanol in rats. The $ED_{50}$ value of 62 mg/kg p.o was estimated. These results suggest that AU-164 is a potent, selective and reversible gastric $H^+/K^+$ ATPase inhibitor, and that AU-164 has a potential use for the clinical therapeutics of peptic ulcer disease.

• Bulletin of the Korean Chemical Society
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• 제23권3호
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• pp.454-458
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• 2002

Furo[3,2-h]quinoline derivatives were synthesized as a gastric $H^+$/$K^+$-ATPase inhibitors. The oxycyclization of 7 and 8-positions in quinoline potentiated the inhibitory activity, while no significant changes in biological activity were observed by the variation of substituents in furan ring. The several furo[3,2-h]quinoline derivatives were worthy of in vivo investigation for their anti-secretory and anti-ulcer activity.

• Archives of Pharmacal Research
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• 제19권2호
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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.

• Biomolecules & Therapeutics
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• 제3권3호
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• pp.205-209
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• 1995

The novel compound KH 3218 was synthesized and evaluated for its ability to inhibit the gastric H$^{＋}$＋ $K^{＋}$ ATPase activity in vitro as well as to lessen gastric acid secretion in vivo. KH 3218 inhibited rabbit gastric H$^{＋}$＋ $K^{＋}$ ATPase in a concentration and time dependent manner. $IC_{50}$/ value was estimated to be about 15 $\mu$M. The inhibition of the H$^{＋}$＋ $K^{＋}$ ATPase by KH 3218 was blocked by sulfhydryl reducing agents, dithiothreitol or $\beta$-mercaptoethanol. The inhibition of the enzyme was not reversible by 50 fold dilution of the incubation mixtures, suggesting the irreversible nature of the inactivation. In the pylorus-ligated rift, KH 3218 reduced the total acid output as compared with the control. In addition, KH 3218 was capable of inhibiting H. pylori urease activity. These data suggest that KH 3218 is a potent inhibitor for H$^{＋}$＋ $K^{＋}$ ATPase activity as well as for gastric acid secretion, and has a potential to be developed as a novel antiulcer agent.

• Bulletin of the Korean Chemical Society
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• 제22권11호
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• pp.1217-1223
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• 2001

A series of benzimidazole derivatives containing oxycyclic pyridine was prepared and evaluated for their gastric H+ /K+ -ATPase inhibitory activity. Several of the synthesized compound exhibited potent antisecretion in pylorus-ligated rats when administered intradoudenally. Their inhibitory activities were equivalent or comparable to omeprazole.

• Biomolecules & Therapeutics
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• 제23권5호
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• pp.458-464
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• 2015

Sennoside A (erythro) and sennoside B (threo) are dianthrone glycosides and diastereomers. We investigated their abilities to prevent the gastric lesions associated with diseases, such as, gastritis and gastric ulcer. To elucidate their gastroprotective effects, the inhibitions of $HCl{\cdot}tOH$-induced gastritis and indomethacin-induced gastric ulcers were assessed in rats. It was observed that both sennoside A and sennoside B increased prostaglandin $E_2$ ($PGE_2$) levels and inhibited $H^+/K^+$-ATPase (proton pump). In a rat model, both compounds reduced gastric juice, total acidity and increased pH, indicating that proton pump inhibition reduces gastric acid secretion. Furthermore, sennoside A and B increased $PGE_2$ in a concentration-dependent manner. In a gastric emptying and intestinal transporting rate experiment, both sennoside A and sennoside B accelerated motility. Our results thus suggest that sennoside A and sennoside B possess significant gastroprotective activities and they might be useful for the treatment of gastric disease.

• Bulletin of the Korean Chemical Society
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• 제25권7호
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• pp.1091-1094
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• 2004

• Biomolecules & Therapeutics
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• 제7권4호
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• pp.362-370
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• 1999

Propolis, a natural resinous compound collected from honey bees, contains many biochemical constituents(wax, flavonoids, phenolic compounds, etc.) and has been used in traditional medicines as early as 300 B.C. It was been demonstrated that ethanol, acetylsalicylic acid, ischemia reperfusion, non-steroidal antiin-flammatory drugs and stress induce gastric lesions by promoting the generation of reactive oxygen metabolites. Therefore, some drugs that are capable of scavenging or inhibiting the generation of reactive oxygen radicals might be expected to prevent the gastric mucosal injury. The aim of this study was 1) to examine the antiulcer effect of propolis, 2) to investigate the mechanism of action by determining gastric acid secretion, lipid per-oxidation, mucus content and proton pump ($H^+$/$K^+$-ATPase) activity on gastric mucus in varios experimental models, and finally, 3) to isolate and identify the pure compounds that exert antiulcer activity. Step 2-1 and 2-3 sub-sub fraction shoed a significant reduction of severity of gastirc damage at the dose of 25 mg/kg in various experimental models. We isolated 4 sub-sub-sub fractions by flash column chromatography of Step 2-1 sub-sub fraction and one sub-sub-sub fraction by recrystalization of Step 2-3 sub-sub fraction. The protective effects of propolis sub-sub-sub fraction manifested sifnificant effects in HCl-ethanol induced gastric erosion model and aspirin induced gastric ulcer model. These results showed that the gastric mucosal protective effect of propolis might result from the increase of mucus secretion, free radical scavenging effect as well as the reduction of acid secretion in accordance with the reduction of $H^+$/$K^+$-ATPase activitv. Three compounds were isolated and identified from sub-sub fraction of propolis which showed antiulcer effects. Subsequently, these compounds were identified as a flavonoid, namely, 2-acetoxy-5,7,-dihydroxy-flavanone, galangin and chrysin.

• 한국식품위생안전성학회지
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• 제14권4호
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• pp.358-364
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• 1999

벌집으로부터 채취한 수지상의 물질인 propolis는 다양한 생화학적 성분을 함유하며 기원전 300년부터 사용되어 온 전통약물이다. 최근 항균, 항 바이러스, 항진균, 국소마취, 면역 활성, 항염, 항산화 작용등의 생물학적 활성이 보고된 바 있다. 본 연구에서는 위염과 위궤양에 미치는 propolis추출물과 분획물의 약조학적 효과를 평가하고자 에탄올 추출물을 hexane, toluene, ethyl acetate로 분획하여 항위염 및 항위궤양 활성을 조사하였다. Propolis 에탄을 추출물은 염산·에탄을 위손상, Shay의 위액 분비 실험에서 용량 의존적인 보호효과를 나타내었고 hexnae과 toluene 분획물은 염산·에탄을 위손상, aspirin에 의한 위손상, Shay의 위액 분비 실험에서 위손상과 위액분비를 감소시켰다. propolis 추출물과 분획물의 위염 및 위궤양에 대한 보호효과는 H+/K+ATPase activity의 억제에 의한 위액분비의 감소에 의한 것으로 생각된다.

• 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.