Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038358 (gastric ulcer)
 5,179 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gastroprotective activity of the diterpene ferruginol isolated from Prumnopitys andina wood and bark was determined on HCl/EtOH-induced gastric lesions in mice. The effect of the compound on the healing of subacute gastric lesions in rats was also studied. The mode of action of the diterpene was assessed using human gastric epithelial cells (AGS) and MRC-5 fibroblasts. The effect of ferruginol on the prostaglandin E2 content, protection against sodium taurocholate induced-damage and reduced glutathione content was evaluated on AGS cells as well as on the growth of AGS and fibroblast cultures. The free radical scavenging effect of ferruginol was assessed by the 1,1-diphenyl-2-picryl-hydrazil radical and superoxide anion assays. The effect of ferruginol on human erythrocyte membrane lipoperoxidation was determined. The cytotoxicity of the compound was assessed by means of the neutral red uptake. At 25 mg/kg, ferruginol inhibited the appearance of gastric lesions by 60% showing similar effects than lansoprazole at 20 mg/kg. Additionally, the compound displayed a significant ulcer healing activity in rats at 25 and 50 mg/kg with curative ratios of 36.0% and 92.5%, respectively, while the reference compound ranitidine at 50 mg/kg showed a curative ratio of 79.6%. At 6 and 12 microM, ferruginol increased significantly the prostaglandin E2 content. A strong inhibition of lipoperoxidation was found (IC50: 1.4 microM), but no effect was observed on the sodium taurocholate induced-damage or reduced glutathione content. Ferruginol stimulated cell proliferation at 1-2 microM in AGS cells and at 4-8 microM in fibroblasts, with cytotoxicities (IC50) of 24 and 26 microM, respectively. Our results support that ferruginol acts as gastroprotective increasing the PGs content, protecting the cells against lipid peroxidation and improving the gastric ulcer healing by a stimulating effect on the cell proliferation. These findings encourage further pharmacological studies of ferruginol as a potential new anti-ulcerogenic drug.
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PMID:Gastroprotective and ulcer healing effect of ferruginol in mice and rats: assessment of its mechanism of action using in vitro models. 1630 8

This study was designed to determine the effect of Mangifera indica flowers decoction, on the acute and subacute models of induced ulcer in mice and rats. A single oral administration of the aqueous decoction (AD) from M. indica up to a dose of 5 g/kg, p.o. did not produce any signs or symptom of toxicity in the treated animals. The oral pre-treatment with AD (250, 500 and 1000 mg/kg) in rats with gastric lesions induced by ethanol, decreased the gastric lesions from 89.0+/-6.71 (control group) to 9.25+/-2.75, 4.50+/-3.30 and 0, respectively. Pretreatment with AD (250, 500 and 1000 mg/kg) to mice with HCl/ethanol- or stress-induced gastric lesions resulted in a dose-dependent significant decrease of lesion index. In the piroxicam-induced gastric lesions, the gastroprotective effect of AD was reducing with the increase of the AD dose. In the pylorus-ligature, AD (p.o.) significantly decreased the acid output indicating the antisecretory property involved in the gastroprotective effect of M. indica. Treatment with AD during 14 consecutive days significantly accelerated the healing process in subacute gastric ulcer induced by acetic acid in rats. Pretreatment with N-nitro-l-arginine methyl ester (l-NAME), an inhibitor of NO-synthase, did not abolish the gastroprotective effects (99% with saline versus 80% with l-NAME) of AD against ethanol-induced gastric lesions. Pretreatment with N-ethylmaleimide (NEM), a blocker of endogenous sulphydryl group, significantly abolished the protective effects of AD against ethanol-induced gastric ulcers (95% with saline versus 47% with NEM). Phytochemical screening showed the presence of steroids, triterpenes, phenolic compounds and flavonoids. Estimation of the global polyphenol content in the AD was performed by Folin-Ciocalteu method and showed approximately 53% of total phenolic on this extract. These findings indicate the potential gastroprotective and ulcer-healing properties of aqueous decoction of M. indica flowers and further support its popular use in gastrointestinal disorders in Caribbean.
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PMID:Can the aqueous decoction of mango flowers be used as an antiulcer agent? 1650 58

Several plants are used in folk medicine to treat gastrointestinal disorders. Mouriri pusa Gardn. (Melastomataceae) is a medicinal plant commonly used in the central region of Brazil against gastric ulcer. Two organic extracts methanolic (MeOH) and dichloromethane (DCM) obtained by sequential extraction from the leaves of Mouriri pusa were evaluated for their ability to protect the gastric mucosa against injuries caused by necrotizing agents (0.3M HCl/60% EtOH, absolute ethanol, non-steroidal anti-inflammatory drug, stress and pylorus ligature) in mice and rats. The best results were obtained after pretreatment with MeOH extract whereas the DCM extract did not show the same significant antiulcerogenic activity. No acute toxicity was observed in animals treated with 5 g/kg, p.o. of MeOH extract. The mechanism involving the antiulcerogenic action of MeOH extract seemed to be related to NO generation and also suggested the effective participation of endogenous sulfhydryl group in the gastroprotective action. Phytochemical investigation of the MeOH extract of Mouriri pusa yielded tannins, flavonoids and (-)-epicatechin. The presence of these phenolic compounds probably would explain the antiulcerogenic effect of the polar extract of Mouriri pusa leaves.
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PMID:Effect of Mouriri pusa extracts on experimentally induced gastric lesions in rodents: role of endogenous sulfhydryls compounds and nitric oxide in gastroprotection. 1669 6

The gastroprotective effect of the sesquiterpene cyperenoic acid and seven semi-synthetic derivatives was assessed in the HCl/ethanol-induced gastric ulcer model in mice. At doses of 25, 50 and 100 mg kg(-1), cyperenoic acid showed a dose-dependent gastroprotective effect reducing the lesions by 45 and 75% at 50 and 100 mg kg(-1), respectively. Seven derivatives of the sesquiterpene were prepared and their gastroprotective activity compared at 50 mg kg(-1). The cytotoxicity of the compounds was evaluated in fibroblasts and AGS cells. At 50 mg kg(-1), patchoulan-15-oic acid (compound 8) presented the best gastroprotective effect, reducing the gastric lesions by 86%, with a similar effect to lansoprazole at 20 mg kg(-1). The gastroprotective effect of cyperenol, cyperenoic acid methyl ester and the ethylamide and butylamide from cyperenoic acid were in the same range, reducing the gastric lesions by 72-77%. Cyperenol and cyperenoic acid methyl ester, however, were more cytotoxic with IC50 (concentration that produces a 50% inhibitory effect) values of 44 and 75, 48 and 75 microM against AGS cells and fibroblasts, respectively. The best gastroprotective effect with lower cytotoxicity was found for the compound 8, cyperenoic acid and the p-anisidyl derivative 7.
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PMID:Gastroprotective activity and cytotoxic effect of cyperenoic acid derivatives. 1713 14

The ethanol extract of Toona ciliata Roemer (heart wood) was evaluated for its anti-ulcer activity against aspirin plus pylorous ligation induced gastric ulcer (antisecretory), HCl-ethanol induced ulcer (cytoprotective) and water immersion stress induced ulcer in rats. We found that Toona ciliata extract at a dose of 300mg/kg p.o. markedly decrease the incidence of ulcers in all the three models. Ethanol extract of Toona ciliata showed significant reduction in gastric volume, free acidity, total acidity and ulcer index. The plant extract also showed gastro protective activity (52.94%), whereas standard drug sucralfate showed 94.85%. Toona ciliata extract showed protection index 43.0% in water immersion stress induced ulcer, whereas standard drug omeprazole showed protection index 100%.
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PMID:Anti-ulcer activity of crude alcoholic extract of Toona ciliata Roemer (heart wood). 1713 60

Orostachys japonicus (Crassulaceae) herbal preparations have been used to treat gastric ulcer or gastric cancer disease in Korean folk medicine. To demonstrate the effects of the methanol (MeOH) extract of O. japonicus and its fractions on gastric lesions and pain, the MeOH extract was fractionated into triterpene-rich and flavonoid-rich (FRF) fractions. Second, the fractions were subjected to analgesic assays including hot plate and writhing assays and anti-ulcerogenic assays in HCl/ethanol-induced- and indomethacin/bethanechol-induced ulcer models in mice. In this experiment, it was found that the FRF most significantly reduced ulcerative indices and pain in mice, although the MeOH extract was also effective. Oral administration of the FRF highly reduced the diameter of gastric lesion induced by HCl/ethanol (inhibitory effect, 53%) and by indomethacin/bethanechol (inhibitory effect, 36%) at the 100 mg/kg dose. In addition, oral administration of 200 mg/kg FRF markedly increased the reaction time in the hot plate test by 52% and decreased stretching episodes (45%) in the writhing test. These results suggest that the active component of O. japonicus exhibiting the potent anti-ulcerative and antinociceptive effect is included in the FRF. The anti-ulcerative effects of the MeOH extract and the FRF were also supported by gastric juice and gastric acid volumes and pH in pylorus-ligated mice. Taken together, these results provide evidence-based support for the traditional use of O. japonicus for gastric disease.
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PMID:Anti-ulcerogenic effects of the flavonoid-rich fraction from the extract of Orostachys japonicus in mice. 1815 44

Exposure of stationary phase cells of Saccharomyces cerevisiae to 10 mM HCl (pH approximately 2) resulted in cell death as a function of time (up to 6 h) with most (about 40%-65%) of the cells showing apoptotic features including chromatin condensation along the nuclear envelope, exposure of phosphatidylserine on the outer leaflet of cytoplasmic membrane, and DNA fragmentation. During the first 2 h of acid exposure there was an increase in reactive oxygen species (ROS) level inside cells, with subsequent elevation in the level of lipid peroxidation and decrease in reducing equivalents culminating in loss of mitochondrial membrane potential (DeltaPsi(m)). An initial (1 h) event of mitochondrial hyper-polarization with subsequent elevation of ROS level of the acid treated cells was also observed. S-adenosyl-l-methionine (AdoMet; 1 mM) treatment increased the cell survival of the acid stressed cells. It partially scavenged the increased intracellular ROS level by supplementing glutathione through the transsulfuration pathway. It also inhibited acid mediated lipid peroxidation, partially recovered acid evoked loss of DeltaPsi(m) and protected the cells from apoptotic cell death. S-adenosyl di-aldehyde, an indirect inhibitor of the AdoMet metabolic pathway, increased mortality of the acid treated cells. Incubation of acid stressed cells with the antioxidant, N-acetyl-cysteine (1 mM), decreased the cellular mortality, but the same concentration of AdoMet offered more protection by scavenging the free radicals. The ability of AdoMet to scavenge ROS mediated apoptosis may be an important function of this molecule in responding to cellular stress. The study could open a new avenue for detailed investigation on the curative potential of AdoMet against gastric ulcer.
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PMID:Antiapoptotic role of S-adenosyl-l-methionine against hydrochloric acid induced cell death in Saccharomyces cerevisiae. 1844 88

The diterpene ferruginol has shown a strong protective effect in animal gastric ulcer models. In the present work, we report the gastroprotective effect and cytotoxicity of 16 new semisynthetic ester derivatives of ferruginol. The gastroprotective effect of these compounds was assessed with the HCl/EtOH-induced gastric lesions model in mice and the cytotoxicity was measured using MRC-5 fibroblasts, gastric adenocarcinoma (AGS) and liver hepatoma Hep G2 cells. The compounds were tested for a gastroprotective effect at a single oral dose of 20 mg/kg. The best gastroprotective effect was elicited by ferruginyl nicotinate ( 13), reducing the lesion index by 71 %, while the derivatives ferruginyl chloroacetate ( 2), ferruginyl palmitate ( 6), ferruginyl oleate ( 7), ferruginyl 3,5-dinitrobenzoate ( 11), ferruginyl 3-methylbenzofuran-2-carbonyl ester ( 12), ferruginyl indoleacetate ( 14), ferruginyl indolebutyrate ( 15) and ferruginyl pthalate ( 16) reduced the lesions by 49 - 66 %. The most promising compounds were 11, 13 and 14, presenting a gastroprotective effect higher or similar to that of ferruginol but with a high selectivity towards the tumor AGS cells. Among the three products, the most selective towards AGS cells was 14, followed by 13, and 11 (IC (50) values of 12, 22 and 29 microM, respectively). The isobutyrate 4, inactive as a gastroprotective agent, showed selective cytotoxicity against AGS and Hep G2 cells (IC (50) values of 60 and 39.2 microM, respectively). The cytotoxicity of the above cited compounds towards fibroblasts was >1000 microM. Considering the aliphatic esters of ferruginol, the best gastroprotective activity was found in the C (16) and C (18) derivatives but tended to decrease with increasing aliphatic chain unsaturation. For short-chain esters, the gastroprotective effect could be observed when the chain contained a chlorine atom. For aromatic esters, the presence of nitro groups or a nitrogen atom in the aromatic ring enhanced the gastroprotective activity. The compounds with the best gastroprotective effect and the highest selectivity against tumor cells bear an amino group (indoleacetate and nicotinate) or nitro group (3,5-dinitrobenzoate).
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PMID:New gastroprotective ferruginol derivatives with selective cytotoxicity against gastric cancer cells. 1849 84

On the basis of its temporal and spatial pattern of expression during the healing of gastric ulcers, RegI is implied to be a key growth factor governing the gastric progenitor cell proliferation, which is fundamental for reconstruction of the gastric tissue; however, there is no direct in vivo evidence. The aim of this study was to use RegI-transgenic (Tg) mice to test the role of RegI protein in the healing of experimentally induced gastric ulcers. The stomachs from 48 pairs of wild-type (Wt) and Tg littermates were examined for gastric erosions after 24 h of water-immersion stress, or, 6, 12, 18 and 24 h after oral administration of HCl/ethanol. Expression levels of c-fos and c-myc proto-oncogenes were examined over time by real-time reverse transcriptase PCR to assess gastric cell proliferation. Almost all the littermate pairs tested showed superiority of Tg mice over Wt mice in the ability of decreasing ulcer index (UI) (cumulative length of erosion). The time-course study revealed that the UIs of Tg were lower in the healing phase, and not in the injury phase. The fraction of proliferating cells was higher in Tg mice than in Wt mice throughout the time course as assessed by c-fos expression levels. This is the first in vivo evidence that RegI has a role in gastric ulcer healing. We suggest that RegI exerts its effects by promoting growth and not by cytoprotection.
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PMID:In vivo evidence for the role of RegI in gastric regeneration: transgenic overexpression of RegI accelerates the healing of experimental gastric ulcers. 2015 93

Total nitrogen, volume rate, total HCl and chloride were determined in the gastric juice of 12 patients with gastric cancer and of 17 patients with a clinical diagnosis of peptic gastric ulcer, before and after subcutaneous injection of large doses of histamine. The mean concentration of total nitrogen in the gastric juice of the patients with gastric cancer was significantly higher than in those with gastric ulcer, whereas no significant differences were found between the corresponding mean values of volume rates and concentrations and outputs of total HCl and chloride in the gastric juice of these groups of patients. It is suggested that estimation of total nitrogen concentration in the gastric juice may differentiate between cancer and peptic gastric ulcer of the stomach with a higher degree of certainty than estimation of volume rate, total HCl, or chloride.
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PMID:Total nitrogen in the gastric juice of patients with cancer and peptic ulcer of the stomach. A comparison of volume rate, total HC1, and chloride. 2018 83


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