Shay Rat Research Articles

Gastroprotective effects of methanol extract of Eremomastax speciosa leaf harvested in Southern part of Nigeria in rat

Abstract Gastric ulcer is one of the common cause of hospital consultation with an increasing prevalence worldwide and it is traditionally managed with herbal medicine in the developing countries. This study investigated the gastroprotective effects of methanol extract of Eremomastax speciosa leaf in rats. Cold maceration in 80% methanol was adopted during extract preparation while gas chromatography mass spectroscopy (GC-MS) was employed in the phytochemical analysis. The doses of 25, 50 and 100 mg/kg E. speciosa were used on ethanol-and indomethacin-induced gastric ulcer models in rats. The shay rat method was used to determine the effects of ESE on gastric acidity while the anticholinergic and antihistaminic activities were investigated on isolated rabbit jejunum ex vivo. The GC-MS analysis identified six bioactive compounds. Both ESE and cimetidine significantly (p < 0.05) reduced the severity of indomethacin- and ethanol-induced gastric injuries and gastric acid contents in Shay rats. The extract elicited concentration-dependent relaxation of isolated rabbit jejunum and reduced the contraction induced by both acetylcholine and histamine in the same tissue. The findings showed that ESE protected the rats against chemical-induced gastric ulcer through anticholinergic and antihistaminic mechanisms.

Actividad gastroprotectora del extracto etanólico de hojas de <i>Licania platypus</i> (Hemsl.) Fritish.

La especie Licania platypus, localmente conocida como “sonzapote” se encuentra ampliamente distribuida en países tropicales. Tradicionalmente, en América Central se han utilizado diferentes partes de la planta para diversos problemas de salud, especialmente gastrointestinales. Objetivo: Investigar la posible actividad antiulcerosa gástrica del extracto etanólico de hojas de Licania platypus. Métodos: Las lesiones gástricas fueron inducidas por los modelos de etanol e indometacina. También, se evaluó el extracto con el modelo modificado de Shay. El extracto se administró por vía oral y se midió el área dañada. Además, se analizaron otros parámetros en el modelo de ligadura pilórica. Resultados: La administración oral de una dosis única del extracto (500 mg/kg) redujo significativamente el área de las lesiones gástricas (p < 0.05) en los modelos de inducción de etanol e indometacina. Además, se observó un incremento significativo en la secreción de moco gástrico en el modelo modificado de Shay (p < 0.05). Conclusión: El extracto etanólico de Licania platypus ejerce un efecto gastroprotector en diferentes modelos de inducción de úlceras agudas. Este trabajo brinda la primera evidencia de especies pertenecientes al género Licania con actividad gastroprotectora y permite promover la realización de estudios para elucidar un mecanismo de acción específico.

ANTIULCER ACTIVITY OF AMARANTHUS SPINOSUS LEAF EXTRACT AND ITS COMPARISION WITH FAMOTIDINE IN SHAY RATS

Anti-ulcer activities of petroleum ether, chloroform, Ethanolic extract of Amaranthus spinosus leaf were tested for anti-gastric ulcer activity in Shay rat model. Oral dose of 400mg/kg of ethanolic extract reduced the ulceration and with 800mg/kg body weight ethanolic extract there is the complete absence of ulceration. The anti-gastric activity of ethanolic extract of A.spinosus 800mg/kg body weight was found to be equal to the effect produced by 2mg/kg of Famotidine orally. The reduction in gastric activity was more with Famotidine and the reduction in peptic activity is more with ethanolic extract of A.spinosus . All extracts are safe up to 4000mg/kg. The result of petroleum ether, chloroform and aqueous extract in respect of anti-ulcer activity are less prominent. Keywords: Amaranthus spinosus, Shay rat model, Famotidine, Peptic activity

Antiulcerogenic, Anti-Secretory and Cytoprotective Effects of Piper Cubeba (L.) on Experimental Ulcer Models in Rat

This paper evaluated anti-gastric ulcer and anti-secretory effects of a popular spice Piper cubeba L, (Family: Piperaceae) in rats. The gastric ulcer protective potential of an aqueous suspension of Piper cubeba (PCS) was evaluated against different acute gastric ulcer models in rats induced by pyloric ligation (Shay), hypothermic restraint stress, indomethacin and by necrotizing agents (80% ethanol, 0.2 M NaOH and 25% NaCl) induced gastric mucosal injury. Piper cubeba aqueous suspension (PCS) at the doses 250 and 500 mg/kg body weight administered orally (intraperitoneally in Shay rat model) showed a dose-dependent ulcer protective effects in all the above models. Besides, the PCS offered protection against ethanol-induced depletion of gastric wall mucus (GWM); replenished the reduced non-protein sulfhydryls (NP‑SH) concentration and significantly replenished malondialdehyde (MDA) contents in the gastric tissue. Ethanol induced histopathological lesions of the stomach wall characterized by mucosal hemorrhages and edema was reversed by Piper cubeba aqueous suspension treatment. Pretreatment of rats with Piper cubeba provided significant protection of gastric mucosa through its antioxidant capacity and/or by attenuating the offensive and by enhancing the defensive factor.

Possible biochemical effects following inhibition of ethanol-induced gastric mucosa damage by Gymnema sylvestre in male Wistar albino rats

Context: Gymnema sylvestre (GS) R. Br. (Gymnema) (Asclepiadaceae) has been used from ancient times as a folk medicine for the treatment of diabetes, obesity, urinary disorder, and stomach stimulation.Objective: The present study was designed to investigate the effects of G. sylvestre leaves ethanol extract on gastric mucosal injury in rats.Materials and methods: Gastric mucosal damage was induced by 80% ethanol in 36 h fasted rats. The effect of G. sylvestre on gastric secretions induced in Shay rats was estimated. In stomach, wall mucus, non-protein sulfhydryl groups (NP-SH), malondialdehyde (MDA), total proteins and nucleic acids levels were estimated. Histopathological changes were observed.Results: G. sylvestre pretreatment at doses of 100, 200 and 400 mg/kg provided 27, 49, and 63% protection against the ulcerogenic effect of ethanol, respectively. Pylorus ligation accumulated 10.24 mL gastric secretions with 66.56 mEq of acidity in control rats. Pretreatment with G. sylvestre significantly inhibited the secretions volume and acidity in dose-dependent manner. Ethanol caused significant depletion in stomach-wall mucus (p < 0.001), total proteins (p < 0.01), nucleic acids (p < 0.001), and NP-SH (p < 0.001) levels. Pretreatment with G. sylvestre showed protection against these depleted levels in dose-dependent manner. The MDA levels increased from 19.02 to 29.22 nmol/g by ethanol ingestion and decreased with G. sylvestre pretreatments in dose-dependent manner.Conclusion: The protective effect of G. sylvestre observed in the present study is attributed to its effect on mucus production, increase in nucleic acid and NP-SH levels, which appears to be mediated through its free radical scavenging ability and/or possible cytoprotective properties.

Effects of sea buckthorn (Hippophaë rhamnoides L.) pulp oils on the gastric secretion, gastric emptying and its analgesic activity

Sea buckthorn (Hippophae rhamnoides L.) pulp oils (SBPO) were evaluated for its effect on gastric secretory function, gastric emptying and analgesic activity, as a potential treatment for stomach discomfort and gastric ulcers. The actions of SBPO on gastric acid, pepsin and mucus secretions were studied in Shay rats. SBPO, when administered for 7 days at the dose of 3.5 and 7.0 ml/kg, caused a significant decrease in gastric volume, total acidity and pepsin output. There was also a significant increase in gastric mucus production. Gastric emptying was studied using a carboxymethyl cellulose solution as a non-nutrient meal in mice. SBPO caused a significant decrease in gastric emptying. The antinociceptive effect was evaluated using the acetic acid induced writhing test. SBPO significantly inhibited the number of writhing responses. These results suggest effectiveness of SBPO in stomach discomfort and gastric ulcers. Key words: Hippophae rhamnoides, Sea buckthorn pulp oil, gastric secretion, gastric emptying, antinociceptive effect.

Silymarin, an antioxidant bioflavonoid, inhibits experimentally-induced peptic ulcers in rats by dual mechanisms.

Introduction:Antioxidants are reported to have antiulcer activity. We investigated silymarin, a bioflavonoid antioxidant, for antiulcer potential.Materials and Methods:Pylorus-ligated Shay rats (n=5) were used as the experimental gastric ulcer animal model. The rats, separated into three groups, were administrated silymarin (50 mg/kg), omeprazole (3.6 mg/kg), or saline (5 ml/kg) per orally daily for 5 days prior to ulcerogenic challenge. Nineteen hours after the challenge, the rats were sacrificed and their stomachs isolated. Formed gastric juice was collected for measurement of volume, titrimetric estimation of free and total acidity, and total acid output by the conventional methods. The ulcer index was calculated. Total acid output and free and combined acid quantities were calculated using the acidity value and the volume of formed gastric juice.Results:Silymarin exerted significant (P<.05) antiulcer activity (the ulcer index was reduced to 7.4 ± 1.0 from the control value of 19.8 ± 4.1). Silymarin also significantly reduced free and total acidity, gastric juice volume, total acid output, and combined acid content. The results were analyzed by ANOVA and Newman–Keuls multiple comparison test.Conclusion:This study demonstrates that silymarin has significant antiulcer activity. It perhaps acts by decreasing hydrochloric acid output and increasing buffering power (combined acid).

Anti-ulcerogenic properties of Quassia amara L. (Simaroubaceae) standardized extracts in rodent models

Quassia amara L. is commonly used in Costarican folk medicine. It has been used for the treatment of a broad range of gastrointestinal symptoms such as dyspepsia, gastritis and constipation. In this study, the gastroprotective activity of two standardized extracts of Quassia amara L., Lipro(®) and Ligas(®), was evaluated. Anti-ulcerogenic properties were evaluated in female rats under acute ulcer-induction models (ethanol, indomethacin and hypotermic restraint). To get a deeper insight in the anti-ulcerogenic properties of the extracts, Ligas(®) was evaluated in the Shay rat model. Five parameters were estimated with this model: gastric mucus barrier, non-protein sulfhydril groups (NPSG) in the gastric mucosa, and pH, total acidity and peptic activity of the gastric juice. Induction of ulcers by 95% ethanol (0.5 mL per os), indomethacin (100 mg/kgs.c.) and stress (2h in hypothermic restraint) was inhibited significantly with administration of Lipro(®) (p<0.05), in a dosage range from 4.9 mg/kg/d to 48.9 mg/kg/d. Treatment was given for one week. The extract Ligas(®) showed a significant augmentation of NPSG (p<0.05) in a dosage range from 4.0 to 39.7 mg/kg. Ligas(®) did not produce a significant change (p>0.05) in the other indicators. Quassia amara L. standardized extracts, Lipro(®) and Ligas(®), showed an important anti-ulcerogenic effect in acute ulcer induction models. Their effect was related to an increase in gastric barrier mucus and non-protein sulfhydril groups.

Gastric antiulcer, antisecretory and cytoprotective properties of celery (Apium graveolens) in rats

In the present investigation, an ethanol extract of celery [Apium graveolens L. (Apiaceae/Umbelliferae)], at doses of 250 and 500 mg/kg body weight, was evaluated for antigastric ulcer activity using various experimental gastric ulcer models in rats. Ulcers were induced by indomethacin, cytodestructive agents (80% ethanol, 0.2 M NaOH and 25% NaCl) and cold restraint stress. Gastric secretory studies were undertaken by using pylorus ligation (Shay rat model). In addition to gastric wall mucus (GWM), non-protein sulfhydryl (NP-SH) and malondialdehyde (MDA) were also estimated in gastric tissues after 80% ethanol treatment. Pretreatment of celery extract produced dose-dependent reduction in all experimentally induced gastric lesions. Ethanol (80%) decreased the levels of GWM, NP-SH and increase in MDA concentration in gastric tissue. Celery extract showed the ability to significantly replenish the ethanol-induced depleted levels of GWM and gastric mucosal NP-SH. The gastric mucosal MDA level was also significantly lowered in extract pretreated rats. The celery extract showed stomach protection against the models used for ulcerogenesis. Results were further confirmed by using histopathological assessment. The phytochemical screening showed the presence of various chemical constituents such as flavonoids, tannins, volatile oils, alkaloids, sterols and/or triterpenes. Acute toxicity test revealed no deleterious or toxic symptoms or mortality over a period of 14 days. However, the LD50 was found to be 7.55 g/kg, and showed a large margin of safety. The results suggest that Apium graveolens extract significantly protects the gastric mucosa and suppresses the basal gastric secretion in rats, possibly through its antioxidant potential.

Rocket “Eruca sativa”: A salad herb with potential gastric antiulcer activity

To validate gastric anti-ulcer properties of Rocket "Eruca sativa" on experimentally-induced gastric secretion and ulceration in albino rats. Gastric acid secretion studies were undertaken using pylorus-ligated rats. Gastric lesions in the rats were induced by noxious chemicals including ethanol, strong alkalis, indomethacin and hypothermic restraint stress. The levels of gastric wall mucus (GWM), nonprotein sulfhydryls (NP-SH) and malondialdehyde (MDA) were also measured in the glandular stomach of rats following ethanol administration. The gastric tissue was also examined histologically. The extract was used in two doses (250 and 500 mg/kg body weight) in all experiments. In pylorus-ligated Shay rats, the ethanolic extract of Rocket "Eruca sativa L." (EER) significantly and dose-dependently reduced the basal gastric acid secretion, titratable acidity and ruminal ulceration. Rocket extract significantly attenuated gastric ulceration induced by necrotizing agents (80% ethanol, 0.2 mol/L NaOH, 25% NaCl), indomethacin and hypothermic restraint stress. The anti-ulcer effect was further confirmed histologically. On the other hand, the extract significantly replenished GWM and NP-SH levels, as well as the MDA level significantly reduced by extract pretreatment. Rocket extract possesses anti-secretory, cytoprotective, and anti-ulcer activities against experimentally-induced gastric lesions. The anti-ulcer effect is possibly through prostaglandin-mediated activity and/or through its anti-secretory and antioxidant properties.

Antiulcerogenic activity of bark extract of Tabebuia avellanedae, Lorentz ex Griseb

Tabebuia avellanedae is commonly used for the treatment of peptic ulcers. We carried out this study with the ethanolic extract of bark from Tabebuia avellanedae (EET) (30–1000 mg/kg) to determine its gastroprotective activity and to clarify the pathways involved in this effect. Acute gastric ulceration in rats was produced by oral administration of ethanol and ibuprofen. After ethanol administration, the gastric wall mucus was examined. Chronic gastric ulceration was produced by injection of acetic acid in rat gastric subserosa. Anti-secretory studies were undertaken using Shay rat pylorus ligature technique and measurement of enzymatic activity of H +, K +-ATPase in vitro. Administration of EET p.o. or i.p. significantly inhibited gastric mucosa damage induced by ethanol and ibuprofen. The anti-ulcer effect was further confirmed by enhanced gastric mucus production. In pylorus ligature rats, EET significantly reduced the basal gastric acid secretion and total acidity; moreover, it inhibited the increase in total acidity induced by histamine. In addition, EET reduced the activity of H +, K +, ATPase. The results obtained in the present pharmacological assay indicate that this plant has a protective action against gastric lesions, involving the maintenance of protective factors, such as mucus and prostaglandin, besides the reduction of gastric total acidity.

Gastroprotective effect of an aqueous suspension of black cumin Nigella sativa on necrotizing agents-induced gastric injury in experimental animals

Background/AimPrevious studies on “Black seed” or “Black Cumin” Nigella sativa (NS) have reported a large number of pharmacological activities including its anti-ulcer potential. These studies employed either fixed oil, volatile oil components or different solvent extracts. In folkloric practices, NS seeds are taken as such, in the form of coarse dry powder or the powdered seeds are mixed with water. This study examines the effect of NS aqueous suspension on experimentally induced gastric ulcers and basal gastric secretion in rats to rationalize its use by herbal and Unani medicine practitioners.Materials and MethodsThe study was conducted at the Medicinal, Aromatic and Poisonous Plants Research Center, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Acute gastric ulceration was produced by various noxious chemicals (80% ethanol, 0.2 M NaOH, 25% NaCl and indomethacin) in Wistar albino rats. Anti-secretory studies were undertaken in a separate group of rats. Gastric wall mucus contents and non-protein sulfhydryl concentration were estimated, and gastric tissue was examined histopathologically.ResultsAn aqueous suspension of Black seed significantly prevented gastric ulcer formation induced by necrotizing agents. It also significantly ameliorated the ulcer severity and basal gastric acid secretion in pylorus-ligated Shay rats. Moreover, the suspension significantly replenished the ethanol-induced depleted gastric wall mucus content levels and gastric mucosal non-protein sulfhydryl concentration. The anti-ulcer effect was further confirmed histopathologically.ConclusionThese findings validate the use of Black seed in gastropathies induced by necrotizing agents. The anti-ulcer effect of NS is possibly prostaglandin-mediated and/or through its antioxidant and anti-secretory activities.

Aqueous suspension of anise “Pimpinella anisum” protects rats against chemically induced gastric ulcers

To substantiate the claims of Unani and Arabian traditional medicine practitioners on the gastroprotective potential effect of a popular spice anise, "Pimpinella anisum L." on experimentally-induced gastric ulceration and secretion in rats. Acute gastric ulceration in rats was produced by various noxious chemicals including 80% ethanol, 0.2 mol/L NaOH, 25% NaCl and indomethacin. Anti-secretory studies were undertaken using pylorus-ligated Shay rat technique. Levels of gastric non-protein sulfhydryls (NP-SH) and wall mucus were estimated and gastric tissue was also examined histologically. Anise aqueous suspension was used in two doses (250 and 500 mg/kg body weight) in all experiments. Anise significantly inhibited gastric mucosal damage induced by necrotizing agents and indomethacin. The anti-ulcer effect was further confirmed histologically. In pylorus-ligated Shay rats, anise suspension significantly reduced the basal gastric acid secretion, acidity and completely inhibited the rumenal ulceration. On the other hand, the suspension significantly replenished ethanol-induced depleted levels of gastric mucosal NP-SH and gastric wall mucus concentration. Anise aqueous suspension possesses significant cytoprotective and anti-ulcer activities against experimentally-induced gastric lesions. The anti-ulcer effect of anise is possibly prostaglandin-mediated and/or through its anti-secretory and antioxidative properties.

Antigastric Ulcer Studies on ‘Saffron’ Crocus sativus L. in Rats

Saffron, Crocus sativus Linn. (Family Iridaceae) commonly known as Zaa'fran is used as a flavoring agent and an important ingredient of Arabic coffee (Gahwa). It is also used in many gastric ailments. An aqueous suspension of saffron was subjected for evaluating gastric antiulcer activity induced by pylorus ligation (Shay rats), indomethacin and various necrotizing agents including (80% ethanol, 0.2 M NaOH and 25% NaCl) in rats. Gastric wall mucus and non-protein sulfhydryl contents were also estimated in rats. Histopathological assessment of rat stomach was carried out. The saffron aqueous suspension at doses (250 and 500 mg kg 1 ) exhibited decrease in basal gastric secretion and ulcer index in Shay rats and indomethacin treated groups. Gastric wall mucus elevation was observed. No significant histopathological changes were noted. A large margin of safety was observed in animals after acute and chronic treatment.) Saffron exhibited significant antisecretory and antiulcer activities without causing any deleterious effects on acute and chronic toxicity in rodents.

Effect of Commiphora opobalsamum (L.) Engl. (Balessan) on experimental gastric ulcers and secretion in rats

The ulcer protective potential of an ethanol extract of Commiphora opobalsamum (L.) Engl. (Burseraceae) ‘Balessan’ was assessed against different acute gastric ulcer models in rats induced by necrotizing agents (80% ethanol, 0.2 M NaOH and 25% NaCl), hypothermic restraint stress, pyloric ligation (Shay) and indomethacin. Balessan, 250 and 500 mg/kg administered orally (intraperitoneally in Shay rat model) showed a dose-dependent ulcer protective effects in all the above ulcer models. Besides, the extract offered protection against ethanol-induced depletion of stomach wall mucus and reduction in nonprotein sulfhydryl (NP-SH) concentration. Ethanol treatment also caused histopathological lesions of the stomach wall. Pretreatment with Balessan extract provided a complete protection of gastric mucosa through supporting both the offensive and defensive factors. Balessan extract was also showed a large margin of safety without any apparent adverse effects in rats.

Gastroprotective effects of 'Amla' Emblica officinalis on in vivo test models in rats.

An ethanol extract of 'Amla' Emblica officinalis Gaertn. was examined for its antisecretory and antiulcer activities employing different experimental models in rats, including pylorus ligation Shay rats, indomethacin, hypothermic restraint stress-induced gastric ulcer and necrotizing agents (80% ethanol, 0.2 M NaOH and 25% NaCl). Oral administration of Amla extract at doses 250 mg/kg and 500 mg/kg significantly inhibited the development of gastric lesions in all test models used. It also caused significant decrease of the pyloric-ligation induced basal gastric secretion, titratable acidity and gastric mucosal injury. Besides, Amla extract offered protection against ethanol-induced depletion of stomach wall mucus and reduction in nonprotein sulfhydryl concentration. Histopathological analyses are in good agreement with pharmacological and biochemical findings. The results indicate that Amla extract possesses antisecretory, antiulcer, and cytoprotective properties.

The pharmacological studies on matrine and oxymatrine

Matrine and oxymatrine, major components of Sophora flavescens, were confirmed to have a protective effect on restraint and water immersion stress ulcer in mice. Oxymatrine inhibits the formation of some experimental gastric ulcer, pylorus ligation ulcer and indomethacin ulcer, which are considered to relate to acid secretion. Oxymatrine decreases acid secretion in Shay's rats and inhibits gastric motility induced by restraint and water immersion stress when administered intraduodenally. These results suggest that the protective effect of oxymatrine on stress ulcer is possibly due to a decrease of acid secretion and inhibition of gastric motility. In spite of its weak inhibition of gastric acid secretion, intravenous injection of matrine is rather effective for stress ulcer. Matrine exhibits the inhibition of writhing induced by acetic acid, prolongation of sleeping time induced by pentobarbital, hypothermia and inhibition of locomotor activity induced by methamphetamine. Matrine (i.v.) also inhibits gastric motility induced by restraint and water immersion stress. On the other hand, the administration of matrine exhibits clear contraction on the preparation of the fundus strip of rats at high concentration. The contractile response of the fundus strip to matrine is not inhibited by treatment with tetrodotoxin, and is not modified with atropine, while pretreatment of the fundus strip with antihistamine abolished or reduced the contractile response. It can therefore be assumed that the direct action of matrine on the stomach smooth muscle possibly contributes to the mechanism of the matrine induced inhibition of the spontaneous gastric motility and rise in the tone of stomach, and may play an important role in the protection of the restraint and water immersion stress ulcer formetion.

FR145715, a novel histamine H 2 receptor antagonist, with specific anti- Helicobacter pylori activities

The pharmacological profile of N-[3-[2-[ N′-(2-methoxyethyl)guanidino]thiazol-4yl]benzyl-acetamide (FR145715), a novel histamine H 2 receptor antagonist, was examined in both in vitro and in vivo models using experimental animals in comparison with ranitidine. In isolated guinea-pig atria, FR145715 antagonized the effect of histamine on heart rate with approximately three times more potent activity than ranitidine. In in vivo experiments, intraduodenal FR145715 dose-dependently inhibited spontaneous gastric acid secretion in rats (Shay's rats), with a ED 50 value of 18.4 mg/kg, which was comparable to that of ranitidine (30.5 mg/kg). FR145715 also inhibited histamine-stimulated acid secretion in stomach-perfused anaesthetized rats (Schild's rats), when given intravenously and intraduodenally with ED 50 values of 0.59 and 2.72 mg/kg, respectively. Ranitidine displayed more potent activity having respective ED 50 values of 0.10 and 0.17 mg/kg. In Heidenhain pouch dogs, intravenous and oral FR145715 dose-dependently inhibited gastrin-stimulated acid secretion with respective ED 50 values of 0.12 and 0.32 mg/kg, which were similar to those of ranitidine (0.09 and 0.33 mg/kg). In gastric ulcer models, FR145715 dose-dependently inhibited water immersion restraint stress- and acidified aspirin-induced gastric lesions with ED 50 values of 3.2 and 15.1 mg/kg (po), respectively. The comparative compound, ranitidine, also showed beneficial effects on stress-induced gastric ulcers with an ED 50 value of 1.5 mg/kg (po). However, it failed to inhibit acidified aspirin-induced gastric ulcers. FR145715 inhibited HCl-induced gastric lesions in rats, while pre-treatment with indomethacin abolished its beneficial effects, suggesting that FR145715 has a so-called cytoprotective effect which is dependent on endogenous prostaglandin production. In addition to its atypical profile as a histamine H 2 receptor antagonist, FR145715 exhibited strong anti-microbial activities against strains of Helicobacter pylori ( H. pylori) with a mean minimal inhibitory concentration value of 0.32 μg/ml. Moreover, FR145715 showed no anti-microbial effects on 25 other bacteria examined. In addition, in vivo experiments using gnotobiotic piglets infected with H. pylori, FR145715 (16 mg/kg, t.i.d.) completely eliminated the organism with reduced intensity of inflammation, when treated orally for 10 days. These data demonstrate that FR145715 is a novel histamine H 2 receptor antagonist having potent and selective anti- H. pylori activities as well as cytoprotective properties. The present data suggest that FR145715 might be useful for the patients suffering from ulcer relapse, since the drug might be able to eradicate H. pylori in the stomach, which is considered a key factor to cause ulcer recurrence in humans.

Anti-ulcerogenic mechanisms of a lyophilized aqueous extract of Dalbergia monetaria L. in rats, mice and guinea-pigs.

The decoction of Dalbergia monetaria L. is popularly used in Brazil for the treatment of gastric ulcer and the lyophilized aqueous extract (LAE) of D. monetaria has significant anti-ulcerogenic activity and inhibits gastric ulcer lesions induced by pylorus-ligature, ethanol and hypothermic-restraint stress. This work was conducted to identify the antiulcerogenic mechanisms of action of the LAE of D. monetaria. We analysed the effect of the LAE on prostaglandin E2 (PGE2) synthesis and on the characteristics (pH, volume and total acid content) of gastric juice. The antagonism between the LAE and histamine or carbachol was also analysed. The LAE increased gastric mucosal PGE2 synthesis compared with control (89.7+/-21.5 and 52.6+/-11.8 pg mg(-1), respectively) as assayed by enzyme immunoassay in the rat stomach. The LAE reduced the total acid content of gastric juice, but did not modify pH or gastric volume significantly, in Shay rats. Dose-response curves to histamine were shifted to the right in guinea-pig isolated right atria (pD2 values were 5.77+/-0.2 and 5.42+/-0.3, respectively, in the absence and presence of the LAE), with a significant reduction in maximum response (140+/-15.1 and 98+/-13.0, respectively). The same effect was observed when the agonist was isoprenaline. The LAE had no effect on the dose-response curve to carbachol in rat fundus strips. Thus, the protective effect of the LAE on induced gastric lesions might be because of synergistic effects, e.g. increased PGE2 synthesis and antagonism of H2 histamine and beta-adrenergic receptors, reducing gastric acid secretion. Increased PGE2 synthesis results in increased protection, and antagonism of H2 histamine and beta-adrenergic receptors reduces aggressive factors against the gastric mucosa.

Interferon-inducer polyriboinosinic-polyribocytidylic acid: a potent anti-gastric ulcer agent and inhibitor of the gastric proton pump in rats.

1. Polyriboinosinic-polyribocytidylic acid (Poly I:Poly C), an interferon inducer was studied for its effect on gastric ulceration in rats. Polyriboinosinic-polyribocytidylic acid (1, 2 and 4 mg/kg, i.m.) showed a dose-dependent inhibition of gastric ulcers induced by aspirin, cold restraint stress and pylorus ligation (Shay's model). Protective dose (PD50) +/- SEM values of Poly I:Poly C on these models of ulcers were 1.9 +/- 0.2, 2.3 +/- 0.4 and 2.8 +/- 0.4 (mg/kg, i.m.) respectively. 2. Polyriboinosinic-polyribocytidylic acid (10-60 micrograms) produced dose-dependent inhibition of gastric proton pump (H+/K(+)-ATPase) activity in the gastric parietal microsomal fraction. The concentration of Poly I:Poly C causing a 50% inhibition (IC50) +/- SEM was found to be 17.6 +/- 1.2 micrograms. 3. Polyriboinosinic-polyribocytidylic acid caused a significant decrease in free and total acid and pepsin and an increase in mucin content in Shay (pylorus-ligated) rat. 4. Polyriboinosinic-polyribocytidylic acid did not exert a significant influence on isolated tissue preparations for anti-cholinergic (acetylcholine-induced contraction of guinea-pig ileum) and H2-anti-histaminic (histamine-induced contraction of rat uterus and guinea-pig auricle) activities. 5. Thus, the present study indicates that Poly I:Poly C may possess anti-gastric ulcer activity as a result of inhibition of the gastric proton pump.