Pyloric Ligation-induced Ulcer Research Articles

Evaluation of the Antiulcer Activity of Methanolic Extract and Solvent Fractions of the Leaves of Calpurnia aurea (Ait.) Benth. (Fabaceae) in Rats.

Introduction In Ethiopia, traditionally, the leaves of Calpurnia aurea have been utilized to treat peptic ulcer disease. Therefore, the objective of the present study was to examine the antiulcer activity of Calpurnia aurea hydromethanolic leaf extract and solvent fractions in rats. Methods The ulcer-healing potential of the crude test extract was assessed in rats by adopting pyloric ligation-, acidified ethanol-, and acetic acid-induced ulcer methods; while, in solvent fractions, the acidified ethanol-induced ulcer model was used. In all models, three serial test doses (100, 200, and 400 mg/kg) were given and the antiulcer activity was investigated. Standard drugs like sucralfate (100 mg/kg), omeprazole (20 mg/kg), and cimetidine (100 mg/kg) have been used as a positive control; whereas distilled water (10 mL/kg) was used as the negative control. Parameters like ulcer index, total acidity, pH, gastric volume, and gastric mucin level were all measured. Results In an acute toxicity study, the test extract at the limit test dose (2 g/kg) was safe following a single dose administration. In pyloric ligation-induced ulcers, the plant extract at 200 and 400 mg/kg significantly reduced the ulcer index, the volume of stomach secretion, and total acidity while raising gastric pH and mucus content (P < 0.05). Likewise, in the acidified ethanol- and acetic acid-induced ulcer models, the extract at both test doses (200 and 400 mg/kg) also displayed a substantial reduction (P < 0.05) in ulcer index. Among the fractions, the ethyl acetate fraction revealed remarkable cytoprotective activity at all test doses and the aqueous fraction at 400 mg/kg (P < 0.05). In contrast, the effect of chloroform fraction was found to be negligible. The peak ulcer inhibition was noted at 400 mg/kg of ethyl acetate fraction (52.4%). Conclusion The study showed that the crude extract and solvent fractions possess remarkable antiulcer activity.

Gastroprotective and Healing Effects of Polygonum cuspidatum Root on Experimentally Induced Gastric Ulcers in Rats.

Polygonum cuspidatum is widely used as food and medicine in Korea, China, and Japan. Its major bioactive components, resveratrol and emodin, reportedly protect against gastric lesions. We therefore aimed to investigate: (1) the gastroprotective effects of P. cuspidatum roots in hydrochloric acid/ethanol (HCl/EtOH)- and indomethacin-induced acute gastric ulcer rat models; (2) the healing effects in an acetic acid-induced ulcer model; and (3) potential mechanisms by measuring gastric acid secretion-related parameters in a pyloric ligation-induced ulcer model, and by measuring antioxidant enzyme and prostaglandin E2 levels in the gastric tissue of HCl/EtOH-treated rats. Oral administration of P. cuspidatum extract (PCE) at doses of 100 and 300 mg/kg significantly decreased HCl/EtOH- and indomethacin-induced gastric lesions. PCE at 300 mg/kg significantly reduced gastric lesions in acetic acid-induced ulcers. PCE increased superoxide dismutase (SOD) activity and glutathione (GSH) and prostaglandin E2 levels in gastric tissue, whereas it did not alter gastric acid secretion-related parameters. Our findings indicate that PCE has gastroprotective effects against HCl/EtOH and non-steroidal anti-inflammatory drugs (NSAIDs) and promotes healing of acetic acid-induced ulcers. These gastric mucosal protection and ulcer healing effects are associated with antioxidant effects and the augmentation of prostaglandin E2 and suggest that P. cuspidatum might be a promising preventive and therapeutic agent for treating gastric ulcers.

In vitro antioxidant capacity and in vivo anti-ulcer and analgesic potentials of dichloromethane fraction of stem barks from Boswelli dalzielii Hutch

The present study was conducted to study the in vitro antioxidant, antiulcer and analgesic activities of dichloromethane fraction (DCMF) of stem barks from Boswelli dalzielii Hutch using different models in rats and mice. The antioxidant activity has been evaluated using β-carotene-linoleic acid system and lipid peroxidation and which showed antioxidant capacities. Antiulcer activity of dichloromethane fraction (DCMF) of stem barks from Boswelli dalzielii Hutch was studied in rats by administration of ethanol-induced method and by pyloric ligation method. The analgesic activity of dichloromethane fraction (DCMF) of stem barks from Boswelli dalzielii Hutch (Burseraceae) was tested using the model of acetic acid induced writhing in mice. The present study exhibit maximum radical scavenging activity and has positive effects in a dose dependent manner against ulcer induced by pyloric ligation-induced ulcers and cytoprotective model and analgesic activity using the model of acetic acid induced writhing in mice. The obtained results allow justifying the traditional uses of Boswelli dalzielii Hutch. This present study has clearly supported the utilization of Boswelli dalzielii Hutch in Burkina Faso traditional medicine.

Pharmacokinetic and pharmacodynamic evidence for developing an oral formulation of octreotide against gastric mucosal injury.

Among the somatostatin analogues, octreotide (OCT) is the most commonly used in clinic via intravenous or subcutaneous injection to treat various diseases caused by increased secretion of growth hormone, gastrin or insulin. In order to assesse the feasibility of developing oral formulations of OCT, we conducted systematical pharmacokinetic and pharmacodynamic analyses of OCT in several animal models. The pharmacokinetic studies in rats showed that intragastric administration of OCT had extremely low bioavailability (<0.5%), but it could specifically distribute to the gastric mucosa due to the high expression of somatostatin receptor 2 (SSTR2) in the rat stomach. The pharmacodynamic studies revealed that intragastric administration of OCT dose-dependently protected against gastric mucosal injury (GMI) in mice with WIRS-induced mouse gastric ulcers, which were comparable to those achieved by intravenous injection of OCT, and this effect was markedly attenuated by co-administration of CYN-154806, an antagonist of SSTR2. In pyloric ligation-induced ulcer mice, we further demonstrated that OCT significantly reduced the secretion of gastric acid via down-regulating the level of gastrin, which was responsible for the protective effect of OCT against GMI. Overall, we have provided pharmacokinetic and pharmacodynamic evidence for the feasibility of developing an oral formulation of OCT. Most importantly, the influence of SSTR2 on the pharmacokinetics and pharmacodynamics of OCT suggested that an oral formulation of OCT might be applicable for other clinical indications, including neuroendocrine neoplasms and pituitary adenoma due to the overexpression of SSTR2 on these tumor cells.

Isolation, characterization, and in silico, in vitro and in vivo antiulcer studies of isoimperatorin crystallized from Ostericum koreanum

Context: Ostericum koreanum (Maxim.) Kitagawa (Apiaceae) roots are traditionally used as an analgesic and antiulcer agent. However, the antiulcer potential of isoimperatorin isolated from O. koreanum has not yet been explored.Aim: To evaluate the antiulcer activity of isoimperatorin isolated from the roots of O. koreanum.Materials and methods: Isoimperatorin was isolated as cubic crystals by repeated column chromatography of the ethyl acetate fraction and structure was verified with 1H NMR, 13C NMR and high-resolution mass spectrometry (HRMS-FAB). The crystals obtained were analyzed with the single crystal X-ray method. The MTT assay was used to determine its cytotoxicity against chondrocytes at different concentrations (0.0–737.74 μM, 24 h). The in vivo antiulcer activity of isoimperatorin (40 mg/kg) was determined against ethanol-, indomethacin- and pyloric ligation-induced ulcers in Sprague-Dawley rats. Furthermore, the effect of isoimperatorin (0.0–737.74 μM, 24 h) on the expression of type II collagen in chondrocytes was determined using western blot method. The in vitro urease inhibitory activity of isoimperatorin (0–80 μM) and molecular docking was also performed against urease.Results and discussion: Isoimperatorin demonstrated significant inhibitory activity (IC50 36.43 μM) against urease as compared to the standard drug thiourea (IC50 33.57 μM) without cytotoxic effects. It provided 70.9%, 67.65% and 54.25% protection in ulcer models induced by ethanol, indomethacin and pyloric ligation, respectively. Isoimperatorin showed the highest expression level of type II collagen at 368.87 μM. The docking results confirmed strong binding affinity with the target protein.Conclusion: Isoimperatorin may be used to develop antiulcer drugs with decreased side effects.

Evaluation of the Antiulcer Activity of the Leaves of Azadirachta indica: An Experimental Study

Background:Azadirachta indica, an evergreen tree, is used by several folkloric practitioners to treat peptic ulcers in India. The present study was carried out to evaluate the antiulcer activity of the aqueous extract (AE) of the leaves of A. indica in Wistar rats. Methods: Gastric ulcerations were induced by pyloric ligation, aspirin, and cold restraint stress. AE was used in doses of 150, 300, and 600 mg/kg body weight per os. Distilled water served as the control and ranitidine 20 mg/kg body weight intraperitoneal as the reference standard. The ulcer index (UI) and percentage inhibition (PI) values were determined in each model. The volume of gastric contents, free acidity, total acidity, and pH were measured in the pyloric ligation-induced ulcer model. Results: AE showed a dose-dependent and significant (p < 0.05) decrease in the UI and an increase in the PI in all models employed compared to the control group. AE caused a dose-dependent decline in the gastric content volume, free acidity, and total acidity. Conclusion: The leaves of A. indica possess significant antiulcer activity and act via multiple mechanisms.

Evaluation of the anti-ulcer property of aqueous extract of unripe Musa paradisiaca Linn. peel in Wistar rats

This study investigated the antiulcer activity of aqueous extract of unripe Musa paradisiacal (plantain) peels in rats using ethanol, aspirin, indomethacin and pyloric ligation-induced ulcer models. Fresh peels of M. paradisiaca were extracted in hot water and the yield lyophilised. Distilled water, standard drugs and extract were injected intraperitoneally before inducing ulcer. Lethality test and quantitative phytochemical analyses were also carried out using standard techniques. Results showed that the extract at 50, 100 and 200 mg/kg wt offered 73.87, 80.18 and 81.98% protection, respectively against ethanol-induced ulcer, whereas cimetidine (50 mg/kg) produced 72.07% ulcer protection. There was no significant difference (p > 0.05) between the various groups. The extract also inhibited aspirin-induced ulcer whereas omeprazole (20 mg/kg) significantly enhanced aspirin-induced ulcer. Similar to cimetidine, the extract did not inhibit indomethacin-induced ulceration. Extract (50, 100, and 200 mg/kg) and cimetidine (50 mg/kg) inhibited pyloric ligation-induced ulcer by 100 and 75%, respectively. Findings suggest antiulcerogenic potentials of the extract, thereby supporting its ethnomedicinal use as antiulcer agent. Up to 5000 mg/kg of extract did not cause mortality of the animals, indicating safety of the extract. The extract was rich in flavonoids (1.40 ± 0.02 mg/100 g). Key words: Musa paradisiaca, peptic ulcer, antiulcerogenesis, aspirin-induced ulcer, medicinal plants, flavonoids.

Anti-ulcerogenic and antisecretory effects of Celtis iguanaea (Jacq.) Sargent hexane leaf extract

The Celtis iguanaea (Jacq.) Sargent (Cannabaceae) is one of the native species of the Cerrado region of Brazil widely used in folk medicine to treat dyspepsia. The objective of the present study was to evaluate the gastroprotective effect of the Celtis iguanaea (Jacq.) Sargent (HE) hexane leaf extract in the lesion and gastric secretion models.Antiulcerogenic activity of the Celtis iguanaea (HE) hexane leaf extract was observed with the experimental models, such as indomethacin and pyloric ligation-induced gastric ulcers. In order to evaluate the antisecretory activity of this extract, isolated Rana catesbeiana mucosa and pyloric ligation in mice were used. The HE treatment reduced the lesion index of indomethacin and pyloric ligation-induced ulcer. This extract also reduced the gastric acid secretion and total acidity (increasing the gastric pH) in mice. The secretion of H+ was reduced in the basal values (15.58 ± 1.99 µEq H+/g/15 min) when isolated Rana catesbeiana mucosa was incubated with HE. Intraduodenal administration of HE reduced the gastric secretion produced by bethanecol or histamine. The antiulcerogenic and antisecretory efficacy of HE in this study suggest anticholinergic and antihistaminergic mechanism or interruption of intracellular events that are linked to acid secretion.

Assessment of Anti-Ulcer Activity of Rheum emodii Rhizomes Extract

Purpose: The purpose of the present study was to assess the antioxidant and antiulcer potential of ethanolic extract of rhizomes of R. emodi on Pylorus ligation ulcers. Materials and methods: Variable doses of 50 mg/kg and 100 mg/kg of EERE were administered orally by gavage for evaluating their antioxidant and antiulcer effect on pyloric ligation-induced ulcer in rats. Results: Both doses (50 mg/kg/p.o. and 100 mg/kg/p.o.) was found to reduce the ulcer index along with the reduction in volume and total acidity, and an increase in the pH of gastric fluid in pylorus ligated rats. The increase in the levels of superoxide dismutase (SOD), reduced glutathione (GSH), tissue nitrire/nitrate and gastric adhesion mucus content and decrease in lipid peroxidation (MDA) and MPO activity in both the models showed the antioxidant activity of the R. emodi. It was also found that EERE at a dose of 100 mg/kg/p.o. was more potent as compared to EERE (50 mg/kg/p.o.). Conclusion: The study validates scientifically the widely claimed use of R. emodi as an ethnomedicine to treat ulcers. © 2011 IGJPS. All rights reserved.

Antiulcer and Anti-inflammatory Activity of Aerial Parts Enicostemma littorale Blume

The antiulcer and in vitro anti-inflammatory activities of the aerial parts of Enicostemma littorale against aspirin, ethanol, and pyloric ligation-induced ulcers in rats and bovine serum albumin denaturation were studied. The extract (200 mg/kg and 400 mg/kg po) was administered to the overnight fasted rats, one hour prior to aspirin / alcohol / pyloric ligation challenge. The ulcer index, tissue GSH levels, and lipid peroxidation levels were estimated in all the models of ulcers and the volume of gastric secretion, acidity, and pH, were estimated in the pyloric ligation model of ulcers. Pretreatment with the extract showed a dose-dependent decrease in the ulcer index (Against Aspirin, ethanol challenge, and pyloric ligation. The prior administration of the extract also reduced the total acidity, free acidity, and volume of gastric secretion, and elevated the gastric pH. In addition, it was also observed that the extract inhibited the serum albumin denaturation in a dose-dependent manner. It may be concluded that the methanolic extract possesses antiulcer activity, and the anti-inflammatory activity of the extract may be attributed to the antioxidant potential, as reported earlier.

Evaluation of the antiulcerogenic activity profile of a flavonol diglucoside from Equisetum palustre L.

Ethnopharmacological relevance The aerial parts of Equisetum palustre L. are used to treat peptic ulcer disease in Turkey. In a previous study, a flavonol diglucoside i.e., kaempferol 3- O-1″-β- d-glucopyranosyl-3- O-1″′-β- d-glucopyranoside (KGG) was isolated as the major antiulcerogenic constituent from the plant. Aim of the study The present study was undertaken to evaluate the antiulcer activity profile of KGG using various in vivo experimental ulcer models as well as by assessing gastric biochemical parameters. Material and methods KGG was obtained from the ethanol extract of the aerial parts of the plant by successive chromatographical methods. The activity profile of the compound was investigated using several ulcerogenesis models such as indomethacin-, indomethacin plus HCl/EtOH-, cysteamine-, serotonin-, N G-nitro- l-arginine methyl ester plus EtOH-, diethyldithiocarbamate-, N-ethylmaleimide plus EtOH-, water immersion and restraint stress-, pyloric ligation-induced ulcers. In addition, effects of KGG on the biochemical parameters of gastric juice; i.e., inhibition of titratable gastric acidity, acid output, gastric pH, gastric secretion volume and peptic activity were studied. Results KGG exerted statistically significant gastroprotective activity against indomethacin-, indomethacin plus HCl/EtOH- and N-ethylmaleimide plus EtOH-induced ulcerogenesis. Moreover, KGG demonstrated weak activity against N G-nitro- l-arginine methyl ester plus EtOH, water immersion and immobilization-induced stress, pyloric ligation-induced and diethyldithiocarbamate-induced gastric ulcer models, and also it was ineffective in the prevention of ulcers induced by serotonin and cysteamine. On the other hand, among the gastric biochemical parameters studied, KGG was only found to increase the gastric acid pH from 2.03 to 3.35. Conclusion Results of this investigation have clearly demonstrated that KGG was found to improve the cytoprotective mechanisms of the gastric mucosa. On the other hand, a weak activity profile was observed on the parameters affecting the gastric acidity (water immersion and restraint-induced-, pyloric ligation-induced-ulcerogenesis and titratable acidity).

Evaluation of Antiulcerogenic Activity of Tephrosia calophylla Roots on Aspirin Plus Pyloric Ligation-induced Ulcers in Experimental Rats

Evaluation of Antiulcerogenic Activity of Tephrosia calophylla Roots on Aspirin Plus Pyloric Ligation-induced Ulcers in Experimental Rats

Antiulcerogenic potential of Strychnos potatorum Linn seeds on Aspirin plus pyloric ligation-induced ulcers in experimental rats

Strychnos potatorum (Fam: Loganiaceae) Linn seeds are useful in the treatment of gastropathy in Indian traditional system of medicine. The present study describes the antiulcerogenic potential of S. potatorum Linn seeds on aspirin plus pyloric ligation (Aspirin+PL)-induced gastric ulcer model to substantiate its folklore claim. The seed powder (SPP) and aqueous extract of the seeds (SPE) at two doses 100 and 200 mg/kg, p.o. prevented ulcer formation by decreasing acid secretory activity and increasing the mucin activity in rats. The antiulcerogenic potential was further confirmed by the histopathological studies of stomach mucosa. The results indicate that SPP and SPE exhibit antiulcerogenic activity by both antisecretory and mucoprotective actions. The mucoprotective action of SPP and SPE may be due to the presence of polysaccharides in seeds. The antiulcerogenic potential of SPP and SPE was compared with the standard antiulcer drug, ranitidine.

Anti-gastric Ulcer and Cytoprotective Properties of Caralluma arabica

In the present study, a 10% ethanolic extract of Caralluma arabica, at the doses of 200 and 400 mg/kg, was evaluated for the antigastric ulcer activity using experimental gastric ulcer models induced by phenylbutazone or indomethacin and 80% ethanol or 0.2N NaOH, and cold restraint stress. Some experiments were carried out to study the effects of C. arabica extract on gastric acid secretion in pyloric ligationinduced ulcer and gastric wall mucin production. The 10% ethanolic extract of C. arabica produced a dose-dependent reduction in all experimentally induced gastric lesions used in the present study. The cytoprotective activity of C. arabica in ethanol-induced ulcer was completely abolished by pretreatment with indomethacin. Induction of gastric ulcer reduced gastric wall production of mucin to 50.8% of its initial value. This reduction was completely prevented by pretreatment with C. arabica extract. C. arabica extract significantly reduced total gastric acidity (from 22.4 ± 1.5 to 9.2 ± 1.6 mEq/L) and volume of gastric secretions (from 9.98 ± 0.7 to 2.03 ± 0.2 ml). Results of the present study reveal that the C. arabica extract protects gastric mucosal cells against experimental gastric mucosal damage. This effect confirms results of other studies on Caralluma species and seems to be mediated by multi-mechanisms including increased gastric production of prostaglandins and mucin and reduced gastric acidity.

Alrestatin: gastric acid antisecretory-antiulcer activity in the rat.

Alrestatin sodium (AY-22,284-A) inhibited gastric acid secretion and decreased the volume of gastric juice produced in the pylorus-ligated rat when administered intraperitoneally or perorally. Pentagastrin-induced gastric acid output in the unanesthetized rat was antagonized. The pyloric ligation-induced ulcer formation in the rat was inhibited. Alrestatin sodium did not exhibit an anticholinergic profile. The drug did not block the norepinephrine neuronal uptake mechanism in rat brain or heart; it did not alter the endogenous norepinephrine concentration in the heart and decreased endogeneous brain norepinephrine concentration. Alrestatin sodium is an effective inhibitor of gastric acid secretion and ulcer formation in the rat.