Gastroprotective activity of oleanolic acid derivatives on experimentally induced gastric lesions in rats and mice

The gastroprotective effect of the triterpene oleanolic acid (OA) was assessed on gastric ulceration in rats. The effect of a single oral dose of OA was evaluated at 50, 100 and 200 mg kg(-1) in the following models: pylorus ligature (Shay), and aspirin- and ethanol-induced gastric ulcers. A single oral administration of OA at doses of 50, 100 and 200 mg kg-' inhibited the appearance of gastric lesions induced by ethanol, aspirin and pylorus ligature. In the pylorus ligature and aspirin models, the effect of OA at the selected concentrations was comparable with that of ranitidine at 50 mg kg(-1). In the ethanol-induced gastric lesion model, OA showed a dose-dependent activity, and at 100 and 200 mg kg(-1) was as active as omeprazole at 20 mg kg(-1). The effect of OA, its acetylated and methoxylated derivatives, oleanonic acid and its methyl ester were assessed on HCI/ethanol-induced ulcers in mice at 200 mg kg(-1). OA and its methoxylated (OAM) and acetylated (OAAM, OAA) derivatives proved to be active in this animal model. The semisynthetic derivatives OAM and OAAM had the greatest gastroprotective activity, but their effect was not significantly greater than OA. In an acute toxicity test on mice, intraperitoneal administration of OA showed no toxicity at doses up to 600 mg kg(-1).     

Preventive and curative effects of curcumin on the development of gastric inflammatory diseases in rats

Preventive and curative effects of curcumin on experimental acute and chronic gastric ulcers were investigated to validate its clinical application on a remedy for peptic ulcer. Intraduodenal administration of curcumin, 5–20 mg/kg, inhibited gastric acid secretion in pylorus-ligated rats, and oral administration prevented ethanol-induced acute gastric mucosal lesions. Curcumin (20–80 mg/kg, p.o.) dose-dependently prevented both serotonin-induced gastric mucosal lesions and compound 48/80-induced gastric mucosal lesions in rats. Furthermore, oral administration of curcumin, 10–80 mg/kg, twice daily for 10 days, significantly accelerated the healing of acetic acid-induced chronic gastric ulcer and promoted mucosal regeneration in the ulcerated portion in a dose-related manner. Cimetidine prevented the formation of ethanol-induced gastric mucosal lesions, but not of serotonin-induced and compound 48/80-induced gastric mucosal lesions. Consecutive administration of cimetidine showed a marked acceleration in the healing of acetic acid-induced ulcer. Aminoguanidine, an inducible nitric oxide synthase (iNOS) inhibitor, showed anti-ulcerogenic effects similar to those oberved for curcumin. The present results indicate that curcumin exhibits gastric cytoprotection in the acute lesion models and ulcer healing promotion in the chronic ulcer model. The preventive and curative effects of curcumin might be due to an increase in the mucosal defensive mechanism through its antioxidant property and inhibition of NO or cytokine-mediated inflammation.     

Effects of 5-acetylspiro[benzofuran-2(3H),1'-cyclopropan]-3-one, a new anti-ulcer agent, on experimental acute and chronic ulcers

The effects of 5-acetylspiro[benzofuran-2(3H),1'-cyclopropan]-3-one (AG 629), a newly synthesized compound, on various experimentally induced ulcers were investigated. Oral or intraduodenal administration of AG 629 in a dose range of 25-100 mg/kg inhibited water-immersion stress ulcer, exertion ulcer, Shay ulcer, indometacin- and acetylsalicylic acid (ASA)-induced gastric ulcer, and indomethacin-induced small intestinal ulcer in rats, histamine-induced gastric ulcer in guinea pigs, and ASA-induced gastric ulcer in dogs, though it was not effective against cysteamine-induced duodenal ulcer in rats. AG 629 in doses of 6.3-25 mg/kg p.o. twice a day significantly promoted the healing of acetic acid- or thermal-cortisone-induced gastric ulcers and acetic acid-induced duodenal ulcers in rats. AG 629 (25-100 mg/kg i.d.) inhibited the secretion of gastric acid and pepsin in pylorus-ligated rats and the acid secretion stimulated by distension of the rat stomach with air, whereas this compound did not affect acid secretion stimulated by histamine, pentagastrin, carbachol or 2-deoxy-D-glucose. This study shows that AG 629 has both prophylactic and curative effects on various ulcers. The anti-ulcer effect of this agent seems to be mediated primarily by increasing mucosal resistance and secondarily by an antisecretory activity.     

Anti-ulcer effect of tea catechin in rats

Oral administration of tea catechin dose-dependently prevented absolute ethanol-induced (50, 100, 200 mg/kg) or restraint plus water immersion stress-induced acute gastric mucosal injury (300, 400 mg/kg) in rats. When the effect of test compound was evaluated on the 15th day after acetic acid injection to rats, repeated oral administration of tea catechin (25, 50, 100 mg/kg twice daily) dose-dependently accelerated the healing of acetic acid-induced chronic gastric ulcers. Tea catechin (10(-5)-10(-1) g/100 ml) concentration-dependently scavenged superoxide anions in vitro. Tea catechin (100, 200 mg/kg orally) markedly inhibited the increase in thiobarbituric acid-reactive substances in the injured mucosa of rats treated with 50% ethanol. Tea catechin (50, 100 mg/kg twice orally, daily) markedly inhibited the increase in content of thiobarbituric acid-reactive substances in the ulcerated region of acetic acid-induced gastric ulcers on the 7th and 15th days. In addition, at 50, 100 and 200 mg/kg orally, it dose-dependently prevented the decrease in gastric mucosal hexosamine content induced by absolute ethanol, although it failed to inhibit the basal gastric acid secretion. These results suggest that tea catechin may primarily protect gastric mucosa from acute gastric mucosal injury and promote the healing of chronic gastric ulcers by its antioxidant activity and gastric mucus-increasing actions.     

Effects of 15(R)-15-methyl prostaglandin E2 (arbaprostil) on gastric secretion and various gastric lesions induced in rats

We studied the effects of 15(R)-15-methyl prostaglandin E2 (arbaprostil) on gastric secretion and various acute and chronic gastric lesions produced in rats. Arbaprostil significantly inhibited gastric secretion in 4 hr-pylorus-ligated preparations when given intraduodenally in a dose of 30 or 100 micrograms/kg. The agent, however, significantly stimulated gastric secretion of rats with either a ligated or intact pylorus when given orally in doses of 3-100 micrograms/kg. Orally administered arbaprostil dose-dependently prevented the development of HCI-ethanol-, histamine-, water-immersion stress-, or indomethacin-induced gastric erosions. Intraduodenally administered arbaprostil also dose-dependently prevented the development of aspirin-induced gastric erosions in pylorus-ligated rats. Arbaprostil, given orally in doses of 1-100 micrograms/kg twice daily for 2 weeks, had little or no effect on the healing of acetic acid-induced gastric ulcers. However, oral administration of the agent in a dose of 3 or 10 micrograms/kg twice daily for 4 weeks significantly accelerated the healing of acetic acid-induced gastric ulcers. The increase in doses up to 100 micrograms/kg twice daily for 4 weeks had no effect on ulcer healing. These results indicate that arbaprostil, at either antisecretory or even acid stimulating doses, is effective in preventing the development of acute gastric erosions and in accelerating the healing of chronic gastric ulcers.     

Effects of the new anti-ulcer agent 12-sulfodehydroabietic acid monosodium salt on healing of acetic acid-induced gastric ulcers in rats

The macroscopic and microscopic effects of 12-sulfodehydroabietic acid monosodium salt (TA-2711, CAS 86408-72-2) on the healing of acetic acid-induced gastric ulcers in rats were compared with those of sucralfate and carbenoxolone. Test compounds were given orally twice a day for 10 consecutive days from the day after the injury with glacial acetic acid. TA-2711 (50 and 100 mg/kg) dose-dependently decreased the macroscopic ulcer index (mm2). In addition, at a dose of 100 mg/kg, this drug decreased the length of mucosal defect in the ulcerated region and increased the mucosal regeneration index estimated by microscopic observation. Furthermore, the mucosa surrounding the ulcerated area and the regenerated epithelium in the TA-2711 administered group contained more PAS (periodic acid-Schiff)-positive material than those in the control group. On the other hand, neither sucralfate nor carbenoxolone (100 mg/kg) showed any significant effects on ulcer healing.     

Effects of the new anti-ulcer agent KB-5492 on experimental gastric mucosal lesions and gastric mucosal defensive factors, as compared to those of teprenone and cimetidine.

Effects of KB-5492, a new anti-ulcer agent, on various experimental gastric mucosal lesions and mucosal defensive factors in rats were compared with those of teprenone and cimetidine. KB-5492 administered orally at 12.5-200 mg/kg inhibited water-immersion stress- and indomethacin-induced gastric mucosal lesions in a dose-dependent manner with ED50 values of 46 and 27 mg/kg, respectively, indicating that KB-5492 was more potent than teprenone but less potent than cimetidine. KB-5492, administered orally at 12.5-100 mg/kg, also inhibited ethanol-induced gastric mucosal lesions in a dose-dependent manner with an ED50 of 23 mg/kg, so KB-5492 was 3 times more potent than teprenone, whereas cimetidine produced no obvious inhibition. In addition, KB-5492, administered orally at 25 and 50 mg/kg twice daily for 10 consecutive days, significantly accelerated the healing of acetic acid-induced gastric ulcers more potently than teprenone and cimetidine. KB-5492 at anti-ulcer doses significantly increased gastric mucosal blood flow in normal anesthetized rats and inhibited the reduction of gastric mucosal hexosamine content induced by aspirin, but did not affect gastric acid secretion in pylorus-ligated rats. These results indicate that KB-5492 has potent and broad anti-ulcer properties, which are probably exerted by its enhancement of gastric mucosal defensive factors through increasing gastric mucosal blood flow and/or retaining gastric mucus, and not by its inhibition of gastric acid secretion.     

Effects of a proton pump inhibitor, AG-1749 (lansoprazole), on reflux esophagitis and experimental ulcers in rats

The effects of (+/-)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy-2- pyridyl]methyl]sulfinyl]-1H-benzimidazole (lansoprazole, AG-1749) and famotidine on various experimental ulcers in rats were compared. AG-1749 inhibited reflux esophagitis; gastric lesions induced by water-immersion stress, aspirin or ethanol; and duodenal ulcers induced by cysteamine or mepirizole in a dose-dependent manner: the ID50 values were 0.7, 2.4, 0.7, 8.5, 1.1 and 0.3 mg/kg, p.o. or i.d., respectively. Famotidine inhibited reflux esophagitis with an ID50 value of 12.9 mg/kg, but did not cause 50% inhibition of ethanol-induced gastric lesions even at 100 mg/kg, although it showed almost the same or a little stronger potency on other experimental ulcers: ID50 values were 0.3-1.4 mg/kg. Significant aggravation of ethanol- or water-immersion stress-induced lesions was observed in rats given famotidine at 30 mg/kg twice daily for 4 days, but not in rats given AG-1749 at 10 mg/kg twice daily. Administration of AG-1749 for 14 consecutive days markedly accelerated the healing of acetic acid-induced gastric and duodenal ulcers, and the healing effect was significant at 10 and 30 mg/kg/day, p.o. Famotidine also accelerated the healing of ulcers, but its potency was less than that of AG-1749. The results of this study indicate that although AG-1749 is slightly less potent than famotidine in inhibiting acutely induced gastroduodenal lesions, this agent is superior to famotidine in promoting the healing of ulcers and in inhibiting reflux esophagitis and ethanol-induced gastric lesions.     

Effect of OPC-12759, a novel antiulcer agent, on chronic and acute experimental gastric ulcer, and gastric secretion in rats

The antiulcer effects of OPC-12759, a novel antiulcer agent were compared with those of cetraxate in various experimental ulcer models and on gastric secretion in rats. OPC-12759 (0.3-30 mg/kg, b.i.d., p.o.) significantly accelerated the healing rate of acetic acid-induced gastric ulcer in a dose-dependent manner, while cetraxate did not. When administered orally at 0.3-30 mg/kg, b.i.d., for 7 days, pretreatment with OPC-12759 (0.3-30 mg/kg, b.i.d., p.o.) prevented the formation of acute gastric ulcers, induced by: restraint water immersion stress, aspirin, indomethacin, histamine, serotonin, platelet activating factor (PAF) and DDC. Cetraxate showed antiulcer activity against a part of the OPC-12759-positive gastric ulcer models. Given intraperitoneally at the single dosing range of 10-100 mg/kg, OPC-12759 inhibited the formation of these acute gastric ulcer models. OPC-12759 administered orally at 0.3-30 mg/kg, b.i.d., for 7 days did not inhibit basal gastric secretion in pylorus ligated rats. The results indicated that OPC-12759 possesses wide spectrum antiulcer activity as compared with cetraxate.     

Anti-ulcer effects of chitin and chitosan, healthy foods, in rats

In this study, we compared the effects of low molecular weight (LMW) chitosan (MW: 25,000-50,000), high molecular weight (HMW) chitosan (MW: 500,000-1000,000) and chitin on ethanol-induced gastric mucosal injury and on the healing of acetic acid-induced gastric ulcers in rats. Oral administration of LMW chitosan (250, 500 and 1000 mg/kg) dose-dependently prevented ethanol-induced gastric mucosal injury. Repeated oral administration of LMW chitosan (100, 200 and 400 mg/kg twice daily) also dose-dependently accelerated the gastric ulcer healing. However, the effects of HMW chitosan and chitin on the gastric mucosal injury formation and the gastric ulcer healing were less potent than those of LMW chitosan. LMW chitosan (250 and 500 mg/kg, orally) was ineffective in inhibiting gastric acid secretion in pylorus-ligated rats, although it had a weak acid-neutralizing action. LMW-chitosan (250, 500 and 1000 mg/kg orally) dose-dependently prevented the decrease in gastric mucus content induced by ethanol. These results indicate that of the three compounds, LMW chitosan has the most potent gastric cytoprotective and ulcer healing-promoting actions. In addition, gastric mucus-increasing action of LMW-chitosan may be, at least in part, related to the anti-ulcer effect of this compound.     

Gastroprotective activity of solidagenone on experimentally-induced gastric lesions in rats

The gastroprotective effect of the labdane diterpene solidagenone was assessed on gastric ulcer in rats. The effect of a single oral dose of the compound was evaluated at 50, 100 and 200 mg kg(-1) in the following test systems: pylorus ligature (Shay), aspirin- and ethanol-induced gastric ulcers. In pylorus-ligated rats (Shay model), the ulcerative index decreased by 37% with solidagenone pre-treatment at the three assayed doses. The effect of a single oral dose of 50 mg kg(-1) solidagenone was comparable with ranitidine at the same concentration and similar to higher doses of the compound. A significant effect (P < 0.001) at 100 and 200 mg kg(-1) was observed in the aspirin-induced ulcer model. At both doses, reduction in the number of lesions was approximately 50% compared with controls. The effect was comparable with the reference compound ranitidine (50 mg kg(-1)). With the ethanol-induced gastric ulcers, the effect of solidagenone at 100 and 200 mg kg(-1) was similar to a single oral dose of 20 mg kg(-1) omeprazole with a 50% reduction of the mean number of lesions compared with controls. In acute toxicity tests on mice, intraperitoneal administration of solidagenone showed no toxicity at doses up to 600 mg kg(-1). This is the first report on the gastroprotective activity of a labdane diterpene.     

Effects of the anti-ulcer agents on the amine contents and regulating enzyme activity of gastric mucosa during the healing process of acetic acid induced gastric ulcer in rats

In order to elucidate the action of an H2 blocker (cimetidine) and gastric mucosal protection agents (sucralfate and sofalcone) on the relapse and recurrence of gastric ulcer, the effects of cimetidine, sucralfate and sofalcone on the contents of histamine and serotonin and histidine decarboxylase (HDC) activity in the gastric mucosa were examined in the ulcer region and the intact region at the 10th day after the operation to produce acetic acid-induced gastric ulcer in rats. The following results were obtained: 1) HDC activity in the gastric mucosa of rats treated with cimetidine (100 mg/kg twice daily) tended to increase in the intact region, and it was significantly increased in the ulcer region. 2) Increased HDC activity due to cimetidine treatment was observed at the 10th day after interruption of cimetidine administration. 3) The HDC activity in the gastric mucosa was not changed by the treatment with sucralfate (500 mg/kg/day) and sofalcone (200 mg/kg/day). The results suggest that the increased HDC activity in the gastric mucosa might participate in the relapse and recurrence of gastric ulcer after discontinuation of cimetidine administration.     

Effects of the novel anti-ulcer agent 1-(5'-oxohexyl)-3-methyl-7-propyl xanthine on experimental ulcers and gastric secretion in rats

The effects of 1-(5'-oxohexyl)-3-methyl-7-propyl xanthine (HWA 285) on various experimentally induced ulcers and gastric acid secretion were investigated in rats. HWA 285 (10-50 mg/kg, p.o.) inhibited restraint and water-immersion-induced stress, ulcers, indometacin- and absolute ethanol-induced gastric ulcers and mepirizole-induced duodenal ulcers in rats in a dose-dependent manner. HWA 285 (10-25 mg/kg i.d.) had inhibitory effects on acetylsalicylic acid-induced ulcers. The healing of acetic acid-induced chronic ulcers was significantly accelerated by HWA 285 (25 mg/kg p.o.) when it was given twice daily for 7 consecutive days. When given orally (twice a day, 11 doses in total) before the induction of gastric ulcers by stress, cimetidine at 100 mg/kg aggravated the ulcers, whereas, HWA 285 at 25 mg/kg had not such an effect. In conscious pylorus-ligated rats, HWA 285 (10-100 mg/kg i.p.) showed a dose-dependent inhibition on basal and desglugastrin- and 2-deoxy-D-glucose (2-DG)-stimulated gastric acid secretion. In stomach-lumen perfused rats, HWA 285 (30 mg/kg i.v.) inhibited 2-DG-stimulated gastric acid secretion but not carbachol-stimulated gastric acid secretion. These results suggest that the anti-ulcer effects of HWA 285 are produced by cytoprotective and central anti-secretory activity without peripheral anti-cholinergic properties. Whether the central anti-secretory effects of HWA 285 play thereby the key role, have to be clarified in further investigation.     

Decreased renal excretion of uric acid following diuretic administration in rats

The anti-ulcer effect of sofalcone, an isoprenyl chalcone derivative, on acetic acid-induced gastric ulcers in rats was studied histologically and histochemically. After administrations of sofalcone at 50 and 200 mg/kg twice daily for 10 days, contraction of the ulcer, mucosal regeneration, accelerated development of the collagen fibers in the granulation tissue at the base of the ulcer, and increase of acid mucopolysaccharides, an alcian blue stain-positive substance covering the regenerated mucosa, were noted. The healing effect of sofalcone was balanced in mucosal regeneration and connective tissue proliferation (formation of the collagen fibers). Sofalcone of 50 mg/kg showed a greater healing effect than gefarnate at the same dose and had a similar healing effect as L-glutamine at 200 mg/kg.     

Teprenone promotes the healing of acetic acid-induced chronic gastric ulcers in rats by inhibiting neutrophil infiltration and lipid peroxidation in ulcerated gastric tissues.

Teprenone, an anti-ulcer drug, has been reported to promote the healing of acetic acid-induced chronic gastric ulcers in rats by stimulating gastric mucus synthesis and secretion. Recently, it has been implicated that neutrophil infiltration and lipid peroxidation in ulcerated gastric tissues have an inhibitory effect on the healing of acetic acid-induced chronic gastric ulcers in rats. Therefore, we attempted to clarify whether teprenone exerts a healing-promoting effect on acetic acid-induced chronic gastric ulcers through its inhibitory effect on neutrophil infiltration and lipid peroxidation in ulcerated gastric tissues. In rats with chronic gastric ulcers made by applying acetic acid to the stomach, gastric ulcer healing started later than 3 days after the acetic acid application. Gastric mucosal myeloperoxidase (MPO) activity, an index of tissue neutrophil infiltration, and lipid peroxide content were higher in the ulcerated region than in the intact region on the 8th, 15th, and 22nd day after the acetic acid application. Gastric mucosal non-protein SH content was lower in the ulcerated region than in the intact region on the 8th, 15th, and 22nd day after the acetic acid application, and gastric mucosal adherent mucus content was lower in the ulcerated region than in the intact region on the 8th and 15th day. Daily oral administration of teprenone (100 mg kg(-1)x 2) for 7 or 14 days, starting on the 8th day after the application of acetic acid to the stomach, enhanced the reduction of the ulcer area with attenuation of all these biochemical changes found in the ulcerated region. The teprenone administration caused a decrease in MPO activity and an increase in adherent mucus content in the gastric mucosa of the intact region. These results suggest that the healing-promoting effect of teprenone on acetic acid-induced chronic gastric ulcers in rats could be due not only to stimulation of gastric mucus secretion but also to inhibition of neutrophil infiltration and enhanced lipid peroxidation in the ulcerated gastric tissue.     

The effect of nimesulide on the indomethacin- and ethanol-induced gastric ulcer in rats.

In the present study, we investigated the effects of nimesulide, indomethacin, naproxene, ibuprofen and diclofenac, at anti-inflammatory doses, on the rat gastric tissue (total number = 102). In addition, the effect of nimesulide at doses of 100, 300 and 500 mg kg(-1) on indomethacin-induced and ethanol-induced damage (ulcer) was examined. The potency of nimesulide was compared with that of ranitidine (at 150 mg kg(-1)). Results indicated that nimesulide did not produce any gastric damage. Additionally, it has a therapeutic effect on indomethacin- and ethanol-induced gastric lesions. Ulcer areas were measured in the rats given nonsteroidal anti-inflammatory drugs (NSAIDs). Nimesulide (at doses of 100, 300 and 500 mg kg(-1)) and ranitidine (at a dose of 150 mg kg(-1)) treated completely indomethacin-induced ulcer. The mean ulcer area was 21.9 +/- 8.9 mm(2)in the indomethacin-given control group. Nimesulide and ranitidine reduced the ethanol-induced gastric ulcer. The ulcer area was 114.3 +/- 10.3 mm(2) in the ethanol-given group and it was 4.5 +/- 4.8, 20.1 +/- 1.66, 15.16 +/- 4.05 mm(2) for nimesulide (at doses of 100, 300 and 500 mg kg(-1)), respectively, and 64.16 +/- 3.97 mm(2) for ranitidine.     

A reliable method for the production of antral gastric ulcer by a combination of 2-deoxy-D-glucose, aspirin and ammonia in rats.

In order to establish a reliable method for the production of gastric antral ulcer in rats, combined treatments with three factors: a vagal stimulant, a mucosal barrier breaker and a necrotizing agent were investigated. By the combined administration of 2-deoxy-D-glucose (2-DG; 200 mg/kg, i.v.), aspirin (100-400 mg/kg, p.o.) and hydrochloric acid (0.15 and 0.35 N, 0.5-1.5 ml/100 g, p.o.) or ammonia solution (0.5-1.0%, 0.5-1.5 ml/100 g, p.o.), gastric lesions were prominently induced in sites of both the corpus and antrum on day 2. The largest antral ulcer was induced by the combination of 2-DG (200 mg/kg), aspirin (200 mg/kg) and ammonia solution (1%, 10 ml/kg); and the mean antral ulcer index (mm2) was 43.1 +/- 4.4 and the incidence was 100%. The antral ulcer was found to penetrate the muscularis mucosae and still observed on day 21 and day 28 after ulcer induction in a few cases. From these findings, it was indicated that this antral ulcer would be a useful model for studying the etiology and therapy of gastric ulcer disease.     

Increasing action of teprenone, a new antiulcer agent, on high-molecular-weight glycoprotein in gastric mucus during the healing process of acetic acid-induced ulcer in rats

The effects of teprenone on quantitative changes in gastric mucus glycoprotein during the healing process of acetic acid-induced ulcer in rats were investigated in comparison to those of cimetidine and proglumide. When estimated on the 15th day after operation, teprenone (50 and 100 mg/kg X 2/day, p.o.) significantly decreased the ulcer index by approx. 30%. On the other hand, cimetidine (100 mg/kg X 2/day, p.o.) and proglumide (500 mg/kg X 2/day, p.o.) did not significantly affect it. The high-molecular-weight glycoprotein (HMG, molecular weight of 2 X 10(6) or more) concentration in the gastric mucus of the control group (non-medicated ulcer rats) was 48.7% lower than that of the normal group (non-medicated rats without ulcer). On the contrary, the lower-molecular-weight glycoprotein (LMG, molecular weight between 5 X 10(5) and 2 X 10(6)) concentration of the control group was 95.3% higher than that of the normal group. Teprenone (at both doses) remarkably increased the concentration and secretion of the HMG. In contrast, those of the LMG were decreased by this drug. Cimetidine significantly decreased both the concentration and secretion of the total glycoprotein (HMG + LMG). Proglumide showed only slight increases in the concentration and secretion of the HMG, although it pronouncedly increased the total glycoprotein secretion. These results indicate that teprenone may strengthen the defensive force of gastric mucosa by increasing the HMG with a polymeric structure. In contrast, cimetidine may weaken the mucosal defense.     

Gastric antiulcer activity of Syngonanthus arthrotrichus SILVEIRA

Syngonanthus arthrotrichus SILVEIRA, popularly known as "sempre-vivas mini-saia," is found in mountains of the Espinha?o range in the Brazilian states of Bahia and Minas Gerais. Extracts of this species contain several constituents, including flavonoids which may have antiulcerogenic activity. An ethanolic extract (EEOH), and flavonoid-rich (FRF) and flavonoid-deficient (FDF) fractions obtained from the scapes of S. arthrotrichus were investigated for their ability to prevent ulceration of the gastric mucosa in mice and rats. In the ethanol/HCl-induced ulcer model, lansoprazole (30 mg/kg), EEOH (50, 100, 250 mg/kg) given orally protected the gastric mucosal against injury in mice by 79%, 78%, 73%, and 64% respectively. In the ethanol-induced gastric ulcer model in rats, the lansoprazole (30 mg/kg), FRF and FDF (100 mg/kg) significantly protected the gastric mucosal of rats by 65%, 38% and 25% respectively when compared with the negative control group. In indomethacin/bethanechol-induced gastric ulcers, cimetidine (100 mg/kg) and the EEOH (100, 250 mg/kg) inhibited gastric ulcer formation by 73%, 55% and 32% respectively. In this exactly model other treatments as cimetidine, FRF and FDF (100 mg/kg) each caused 54%, 36% and 45% inhibition, respectively. In the stress-induced gastric ulcer model, cimetidine (100 mg/kg) and the EEOH (50, 100, 250 mg/kg), inhibited gastric ulcer formation by 63%, 73%, 68% and 69% respectively. In the same model, cimetidine, FRF and FDF (100 mg/kg) significantly protected the gastric mucosal of the mice by 60%, 51% and 47% when compared to the control group. In pylorus-ligated mice, cimetidine (positive control) and FRF significantly decreased gastric acid secretion, increased gastric pH and reduced the acid output when compared to the negative control. FDF had no significant effect on these parameters. The protection provided by FRF probably involved an antisecretory mechanism mediated by flavonoids which were absent in FDF. The amount of adherent mucous in the stomach contents was also evaluated with the treatments carbenoxolone (200 mg/kg), FRF and FDF (100 mg/kg) treatment. Each treatments significantly increased the amount of adherent mucous in the gastric juice (8.67+/-1.73, 3.35+/-1.59, 2.1+/-0.41 mg/g of wet tissue, respectively) compared to the control group, indicating a cytoprotective action on the gastric mucosa. Treatment with FRF plus indomethacin and FDF plus indomethacin reduced the prostaglandin biosyntesis (13.6+/-6.5, 27+/-5.5 pg/well) by the mucosa, indicating that the cytoprotective action on the gastric mucosa was not related to the level of prostaglandins. Only FDF (38+/-17 pg/well) maintained the level of prostaglandins and guaranteed the integrity of the mucosa. The results indicate that the EEOH, FRF and FDF have antisecretory and cytoprotective actions, that may be related to the presence of luteoline in the extract and active fractions.     

吡咯-2-甲醛缩N4-(4-甲氧基苯基)氨基脲抗实验性大鼠溃疡作用

化合物Ⅰ具有与呋喃唑酮相似的抗实验性大鼠溃疡活性,但小鼠口服急性毒性较后者小。化合物Ⅰ在剂量为40～100 mg/kg时对五种大鼠溃疡模型(消炎痛型、幽门结扎型、慢性醋酸型、和无水乙醇引起的大鼠溃疡模型)均有较好保护作用,但对水拘急性应激型溃疡无效。对胃酸分泌无明显影响,对胃蛋白酶分泌有轻度抑制作用;具有“细胞保护”样作用,对HCl和无水乙醇引起的大鼠溃疡显示出较好的保护作用;增加幽门结扎大鼠胃液中氨基己糖的含量,降低DNA含量。