Homopterocarpin contributes to the restoration of gastric homeostasis by Pterocarpus erinaceus following indomethacin intoxication in rats

Objective:To investigate the restorative effect of Pterocarpus erinaceus(P.erinaceus) and homopterocarpin.an isoflavonoid isolated from it.on indomethacin-indueed disruption in gastric homeostasis in rats.Methods:Adult rats were dn ided into five groups and lasted for 48 h before treatment.Group I received olive oil(vehicle),group 2 received 25 ing/kg indomethaein while groups 3-5 received cimetidine(100 mg/kg).lioniopterocarpin(25 mg/kg) and P.erinaceus ethanolie stem hark extract(100 mg/kg) respectively.After 1 h.all the groups except group 2 were administered 25 mg/kg of indomethacin.One hour later,the rats were sacrificed and the ulcer index and other gaslroprotective indices were evaluated.Results:Indomethacin caused significant injury to the stomach of the rats as reflected in the ulcer indices(9.0±1.4) as compared with that of control(2.0±0.0).Equally,there were significant increases in gastric acid concentration and malondialdehvde level in the stomachs of the ulcerated animals compared with the control.However mucus content,reduced gluthatione level and gastric pH were significantly reduced in the ulcerated animals compared with the control.Pretreatment with either Pterocarpus bark extract or homopterocarpin reversed the effects of indomethaein on the evaluated parameters.Conclusions:These results indicate that both homopterocarpin and Plerocarpus extract offered gastroprotection against indomethacin-induced ulcer by antioxidative mechanism and the modulation of gastric homeostasis.The results also suggest that homopterocarpin might he responsible for.or contribute to the antiulcerogenic property of P.erinaceus.

Use of proton pump inhibitors in general practice

AIM To evaluate the characteristics of the prescription of the proton pump inhibitor drugs(PPI) and the adherence to the indications of the guidelines regulating thereimbursement limitations set forth by the Italian Drug Agency.METHODS Thirty general practitioners(GP) participated in the study, providing data on more than 40000 patients in total. The population was divided into non occasional users of PPI drugs(PPI users) and non-users(PPI non-users) based on evidence of a prescription of at least 3 packs of PPIs in the last 90 d before analysis. The data provided allowed an assessment of compliance with the requirements of eligibility for PPI reimbursement according to the Italian Drug Agency rules, in order to obtain subpopulations which complied or not with the rules. RESULTS Six thousand three hundred and twenty-two patients were found to be PPI users, accounting for 14.9% of the patient population. PPI users were more frequently female, older and more frequently diagnosed with gastroesophageal reflux disease, gastric or duodenal ulcers, arthropathy, heart disease and cancer than the rest of the population. PPI users had more frequently received prescriptions for non-steroidal ant-inflammatory drugs(NSAIDS), acetylsalicylic acid(ASA), oral anticoagulant therapy(OAT) and systemic steroids. PPI reimbursement resulted applicable to 69.3% of the PPI users, but a potential for reimbursement of PPI prescriptions was identified in the non PPI users for the treatment of peptic or reflux disease(8.5%) and for the protection of gastric damage caused by NSAIDS(6.1%). Patients who are potentially eligible for reimbursement are older, diagnosed with arthropathy and heart disease more frequently and most commonly receive NSAID and ASA prescriptions compared with PPI users who do not satisfy eligibility requirements. Patients in whom it was not possible to identify conditions related to prescription suitability were more frequently associated with use of OAT. CONCLUSION A substantial number of patients who apparently do not meet prescription suitability conditions can be identified, but among non PPI users on the contrary, it is possibleto identify an equal number of patients for whom prescription would be suitable. Poor suitability can be identified in the population receiving OAT. Thus, there is scope for decreasing inappropriate use of PPI drugs by adhering to certain criteria and by involving all interested parties.

Studies on activity of various extracts of Mentha arvensis Linn against drug induced gastric ulcer in mammals

AIM:To examine the antiulcerogenic effects of various extracts of Mentha arvensis Linn on acid,ethanol and pylorus ligated ulcer models in rats and mice.METHODS:Various crude extracts of petroleum ether,chloroform,or aqueous at a dose of 2 g/kg po did not produce any signs or symptoms of toxicity in treated animals.In the pyloric ligation model oral administration of different extracts such as petroleum ether,chloroform and aqueous at 375 mg/kg po,standard drug ranitidine 60 mg/kg po and control group 1 Tween 80,5 mL/kg po to separate groups of Wister rats of either sex(n = 6) was performed.Total acidity,ulcer number,scoring,incidence,area,and ulcer index were assessed.RESULTS:There was a decrease in gastric secretion and ulcer index among the treated groups i.e.petroleum ether(53.4),chloroform(59.2),aqueous(67.0) and in standard drug(68.7) when compared to the negative control.In the 0.6 mol/L HCl induced ulcer model in rats(n = 6) there was a reduction in ulcerative score in animals receiving petroleum ether(50.5),chloroform(57.4),aqueous(67.5) and standard.drug(71.2) when compared to the negative control.In the case of the 90 ethanol-induced ulceration model(n = 6) in mice,there was a decrease in ulcer score in test groups of petroleum ether(53.11),chloroform(62.9),aqueous(65.4) and standard drug ranitidine(69.7) when compared to the negative control.It was found that pre-treatment with various extracts of Mentha arvensis Linn in three rat/mice ulcer models ie ibuprofen plus pyloric ligation,0.6 mol/L HCl and 90 ethanol produced significant action against acid secretion(49.3 ± 0.49 vs 12.0 ± 0.57,P < 0.001).Pre-treatment with various extracts of Mentha arvensis Linn showed highly-significant activity against gastric ulcers(37.1 ± 0.87 vs 12.0 ± 0.57,P < 0.001).CONCLUSION:Various extracts of Mentha arvensis Linn.375 mg/kg body weight clearly shows a protective effect against acid secretion and gastric ulcers in ibuprofen plus pyloric ligation,0.6 mol/L HCl induced and 90 ethanol-induced ulcer models.

Total triterpenes from fruits of Chaenomeles speciosa(Sweet) Nakai protect against indomethacin-induced gastric mucosal injury: involvement of TFF1-mediated EGF/EGFR and apoptotic pathways

OBJECTIVE Gastric ulcers affect people of all ages and half of the world's population,which is being considered as the new"plague of the 21st century".As is well known,gastric mucosa is known as the first guard to protect the stomach from ulcer injury,while the aetiology of gastric ulcer is relative to imbalances between gastric mucosal protective and aggressive factors.Therefore,reducing or eliminating the aggressive factors,returning to the balance of between mucosal protective and aggressive factors,and then restoring the normal functional of gastric mucosal barrier could be crucial for treating the gastric ulcer.The fruits of Chaenomeles speciosa(TCS),also known as"mugua",might be processed into edible and health care derived products,and used as a commonly used traditional medicine in China for thousands of years.In China folk,there is a saying that"apricot one benefit,pear two benefits,mgua hundred benefits",so it has a"hundred-benefit"fruit reputation.Tujia nationality inhabitants in Southwestern China should have rheumatic diseases and peptic ulcers for living in the damp environments and bingeing on spicy and pungent foods.For the exis⁃tence of the fruit derived products of Chaenomeles speciosa as their complementary foods or snacks,the habit makes them rarely suffer from the two kinds of diseases.Enlightened by these,we had investigated the structure-activity rela⁃tionships,screened out CSTT with gastroprotective activity.Our previous studies demonstrated that TCS owned effec⁃tively therapeutic effects on gastric ulcer patients and animals,and further confirmed that TFF1 and apoptotic pathway were closely interrelated with its exerting gastroprotection.However,its underlying molecular mechanisms involved have not been fully elucidated.The current study was to further investigate its protective effect on indomethacin(IND)-damaged RGM-1 cells and rats and its underlying mechanisms through modulating TFF1-mediated EGF/EGFR and apoptotic pathways.METHODS The gastroprotection of TCS was evaluated with IND-induced gastric lesions model in RGM-1 cells and rats.In vitro,the proliferation,migration,mitochondrial viability and apoptosis were assessed,In vivo,ulcer index,ulcer inhibition rate,gastric juice acidity,gastric wall mucus(GWM),histopathology of gastric mucosa were detected.The gastroprotective effects of TCS through the TFF1-mediated EGFR/EGFR and apoptotic pathways were presented and measured by qRT-PCR and Western blotting assays.RESULTS TCS had gastroprotective function,which was related to the amelioration in promoting IND-damaged RGM-1 cell proliferation and migration,hoisting gastric juice acidity and GWM,improving ulcer index and ulcer inhibition rate,attenuating the hemorrhage,edema,epithelial cell loss and inflammatory cell infiltration of gastric mucosa,upregulating proliferation cell nuclear antigen,Bcl-2,Bcl-xl mRNA and TFF1,EGF,p-EGFR,p-Src,pro-caspase-3,pro-caspase-9 protein expressions,mitochondrial viability,mitochondrial cytochrome C concentration and p-EGFR/EGFR,p-Src/Src,Bcl-2/Bax,Bcl-xl/Bad ratioes,downregulating Bax,Bad,Apaf-1 mRNA and cleaved-caspase-3,cleaved-caspase-9,cleaved-PARP-1 protein expressions,cytosol cytochrome C concentration.CONCLUSION TCS′s gastroprotective effect was closely connected with boosting TFF1 expression,acti⁃vating TFF1-mediated EGF/EGFR pathway,thus restraining mitochondrial-dependent apoptosis,which provided new insights into interpreting its underlying mechanism and promised to act as a candidate drug to treat gastric mucosal injury.

Anti-inflammatory and analgesic activities with gastroprotective effect of semi-purified fractions and isolation of pure compounds from Mediterranean gorgonian Eunicella singularis

Objective: To explore anti-inflammatory activities of organic extract and its semi-purified fractions(ethanol, acetone, methanol/dichloromethane) from the Mediterranean gorgonian Eunicella singularis. Methods: The anti-inflammatory and analgesic activities were evaluated, using the carrageenan-induced rat paw edema model and the acetic acid writhing test in mice. The gastroprotective activity was determined using HCl/Et OH induced gastric ulcers in rats. The purification and structure elucidation of compound(s) from the more effective fraction were determined by chromatographic and spectroscopic methods and in comparison with data reported in the literature. Results: The fraction F-Et OH showed an important antiinflammatory activity associated with significant analgesic and gastroprotective properties. The purification and structure elucidation of compound(s) from this fraction lead to the identification of one diterpenoid and four sterols. Conclusions: These results suggested that components from the active fraction can be used to treat various anti-inflammatory diseases.

Gastroprotective effect of Achyranthes aspera Linn,leaf on rats

Objective:The study was aimed al evaluating the antiulcer activity of ethanolic extract of Achyranthes aspera(EEAA) leaf.Methods:The anti-ulcer assays were performed on pylorus ligation and chronic ethanol induced ulcer model.The effects of the EEAA on gastric content volume,pH.free acidity,total acidity and ulcer index were evaluated.Results:The percentage of ulcer protection(59.55%and 35.58%) was significantly(P 【 0.001) higher in the groups treated with the high dose of EEAA(600 mg/kg),it also reduced the volume of gastric juice and total acidity whereas,gastric pH was increased signiGcandy.Conclusions:The results of this study show significant gastroprotective activity of EEAA may be due to presence of phyto-constituents like flavanoids,saponins and tannins.

Synthesis and Evaluation of Glyceride Prodrugs of Naproxen

The glyceride ester derivatives 6a and 6b were prepared by reacting 1,2,3-trihydroxy propane 1,3-dipalmitate/stearate with (S)-naproxen as potential prodrugs. The synthesis was achieved successfully with the aid of N,N’-dicyclohexyl- carbodiimide. These prodrugs were evaluated for anti inflammatory, analgesic and gastroprotective activity. It was found that prodrugs 6a and 6b showed less irritation to gastric mucosa as indicated by ulcer index. The synthesized glyceride esters were found to possess good pharmacological profile as shown by results of anti inflammatory and analgesic activity. The aqueous studies were performed in order to ensure the release of prodrugs. Both prodrugs were found to stable at acidic pH while undergoes hydrolysis at pH 7.4. These findings suggest that the glyceride prodrugs 6a and 6b might be used as potential biolabile derivatives.

An open-label,randomized,cross-over bioequivalence study of lafutidine 10 mg under fasting condition

AIM:To assess the relative bioavailability and pharmacokinetic properties of two formulations(test and reference) of Lafutidine 10 mg.METHODS:The study was performed as an open label,randomized,two-way,two-period,two-treatment,single dose cross-over bioequivalence study,under non-fed condition to compare the pharmacokinetic prof iles of the lafutidine formulation manufactured by Emcure Pharmaceuticals Ltd.,India using an indigenously developed active pharmaceutical ingredient(API) and the commercially available Stogra formulation,of UCB Japan Co.,Ltd.,Japan.The two treatments were separated by a washout period of 5 d.After an overnight fasting period of 10 h,the subjects were administered either the test or the reference medication as per the randomization schedule.Blood samples were collected at intervals up to 24 h,as per the approved protocol.Concentrations of lafutidine in plasma were analyzed by a validated liquid chromatography/tandem mass spectrometry(LC/MS/MS) method,and a non-compartmental model was used for pharmacokinetic analysis.The pharmacokinetic parameters were subjected to a 4-way ANOVA accounting for sequence,subjects,period and treatment.Statistical significance was evaluated at 95% conf idence level(P ≥ 0.05).RESULTS:The mean(±SD) values of the pharmacokinetic parameters(test vs reference) were Cmax(265.15±49.84 ng/mL vs 246.79±29.30 ng/mL,P<0.05),Area under the curve(AUC)(0-t)(1033.13±298.74 ng.h/mL vs 952.93±244.07 ng.h/mL,P < 0.05),AUC(0-∞)(1047.61±301.22 ng.h/mL vs 964.21±246.45 ng.h/mL,P<0.05),and tv2(1.92±0.94 h vs 2.05±1.01 h,P<0.05).The 90% conf idence intervals(CI) for the test/reference ratio of mean Cmax,AUC(0-t),and AUC(0-∞) were within the acceptable range of 80.00 to 125.00.The mean times(± SD) to attain maximal plasma concentration(tmax) of lafutidine were 0.95±0.24 h vs 1.01±0.29 h(P<0.05) for the test and the reference formulations respectively.Both the formulations were well tolerated.

Organic carbon monoxide prodrug, BW-CO-111, in protection against chemically-induced gastric mucosal damage

Metal-based carbon monoxide(CO)-releasing molecules have been shown to exert antiinflammatory and anti-oxidative properties maintaining gastric mucosal integrity.We are interested in further development of metal-free CO-based therapeutics for oral administration.Thus,we examine the protective effect of representative CO prodrug,BW-CO-111.in rat models of gastric damage induced by necrotic ethanol or aspirin,a representative non-steroidal anti-inflammatory drug.Treatment effectiveness was assessed by measuring the microscopic/macroscopic gastric damage area and gastric blood flow by laser flowmetry.Gastric mucosal mRNA and/or protein expressions of HMOX1,HMOX2,nuclear factor erythroid 2-related factor 2,COX1,COX2,iNos,Anxa1 and serum contents of TGFB1,TGFB2,IL1 B,IL2,IL4,IL5,IL6,IL10,IL12,tumor necrosis factorα,interferonγ,and GM-CSF were determined.CO content in gastric mucosa was assessed by gas chromatography.Pretreatment with BW-CO-111(0.1 mg/kg,i.g.)increased gastric mucosal content of CO and reduced gastric lesions area in both models followed by increased GBF.These protective effects of the CO prodrug were supported by changes in expressions of molecular biomarkers.However,because the pathomechanisms of gastric damage differ between topical administration of ethanol and aspirin,the possible protective and anti-inflammatory mechanisms of BW-CO-111 may be somewhat different in these models.

Protective effect of essential oil of Pistacia atlantica Desf. on peptic ulcer: role of α-pinene

OBJECTIVE: To evaluate the efficacy of Pistacia atlantica Desf. oleoresin essential oil on peptic ulcer(PU) and its antibacterial effect on metronidazole-resistant Helicobacter pylori, as well as chemi-cal composition of the essential oil.METHODS: The essential oil was standardized using gas chromatography mass spectrometry(GC/MS) analysis. Acute toxicity of the essential oil was assessed in animal model. In vitro anti-Helicobacter pylori activity was performed through disc diffusion and minimum inhibitory concentration method. For gastroprotective assay, rats received Pistacia atlantica Desf. essential oil(25, 50 and 100 mg/kg orally) 1 h before induction of ulcer by ethanol.Macroscopic(ulcer index and protection rate) and microscopic examination were performed.RESULTS: The GC/MS analysis of the essential oil led to the identification of twenty constituents andα-pinene is predominant constituent. The essential oil was safe up to 2000 mg/kg. All Helicobacter pylori strains were susceptible to the essential oil and the MIC ranged from 275 to 1100 μg/m L. The ulcer index for treated groups was significantly reduced compared to control(P < 0.001) with EC50 value of 12.32 mg/kg. In microscopic examination, Pistacia atlantica attenuated destruction and necrosis of gastric tissue.CONCLUSION: Current study exhibited protective effect of standardized Pistacia atlantica essential oil against ethanol-induced gastric ulcer and its antibacterial activity on Helicobacter pylori. α-pinene might be the responsible agent.

Cumin(Cuminum cyminum)and black cumin(Nigella sativa)seeds:traditional uses,chemical constituents,and nutraceutical effects

Although the seeds of cumin(Cuminum cyminum L.)are widely used as a spice for their distinctive aroma,they are also commonly used in traditional medicine to treat a variety of diseases.The literature presents ample evidence for the biomedical activities of cumin,which have generally been ascribed to its bioactive constituents such as terpenes,phenols,and flavonoids.Those health effects of cumin seeds that are experimentally validated are discussed in this review.Black seeds(Nigella sativa),which are totally unrelated to C.cyminum,have nevertheless taken the name‘Black cumin’and used in traditional systems of medicine for many disorders.Numerous pre-clinical and clinical trials have investigated its efficacy using the seed oil,essential oil,and its main constituent thymoquinone(TQ).These investigations support its use either independently or as an adjunct along with conventional drugs in respiratory problems,allergic rhinitis,dyspepsia,metabolic syndrome,diabetes mellitus,inflammatory diseases,and different types of human cancer.Multiple studies made in the last decades validate its health beneficial effects particularly in diabetes,dyslipidemia,hypertension,respiratory disorders,inflammatory diseases,and cancer.Nigella sativa seeds also possess immune stimulatory,gastroprotective,hepatoprotective,nephroprotective,and neuroprotective activities.TQ is the most abundant constituent of volatile oil of N.sativa seeds,and most of the medicinal properties of N.sativa are attributed mainly to TQ.All the available evidence suggests that TQ should be developed as a novel drug in clinical trials.

Gastroprotective herbs for headache management in Persian medicine:A comprehensive review

The gut-brain axis is a bidirectional communication system that exists between the brain and gut. Several studies claimed that some types of headaches are associated with various gastrointestinal(GI) disorders.In Persian medicine(PM), physicians believed that gastric disturbances could stimulate headache and introduced some herbs for boosting gastric function as a therapeutic remedy for headache. Here we review the current evidence for the gastroprotective and antiheadache effects of herbs used in PM.Herbs used for their gastrotonic effects in PM were identified from selected Persian medical and pharmaceutical textbooks. Pub Med, Scopus and Google Scholar were used to search for contemporary scientific evidence relating to the gastric and neurologic effects of these plants. A total of 24 plants were recorded from the selected sources included in this review, most of which belonged to the Rosaceae family.Phyllanthus emblica, Zingiber officinale, Boswellias errata, Punica granatum and Hypericum perforatum had the most recent studies related to GI disorder and headache, while current research about quince, rose,apple, hawthorn and pear was limited. Reducing Helicobacter pylori growth, gastritis, erosion of the stomach lining, hemorrhage and perforation, improving gastric mucosal resistance, antisecretary, antiulcer,antipyretic, analgesic, sedative, anxiolytic, anti-inflammatory, anticonvulsant, neuroprotective and antioxidant effects as well as improvement in memory scores were some of the gastrotonic and neuroprotective mechanisms described in the current research. These results confirmed that medicinal plants prescribed in PM may improve headache in patients through the management of GI abnormalities.However, further studies are recommended to investigate the efficacy and safety of the mentioned medicinal plants.

Gastroprotective Effects of Ascaridole on Gastric Ulcer in Rats

Objective To evaluate the gastroprotective activity of ascaridole. Methods The gastroprotective effect of ascaridole was evaluated on ulcer healing in rats with acetic acid-induced chronic gastric ulcer, pylorus ligation- and Aspirin-induced gastric ulcer. Ascaridole was ig administered with the dosages of 10 and 20 mg/kg once daily for 7 d. Results Ascaridole showed the significant anti-ulcer effects. In acetic acid-induced gastric ulcer rats, the ulcer areas after 10 and 20 mg/kg of ascaridole treatment were (65.1 ± 20.0) and (50.6 ± 11.0) mm2, respectively, which were significant lower (P < 0.01) than that of the control group [(116.7 ± 35.8) mm2]. For pylorus ligation model, ascaridole showed a gastric ulcer healing effect in a dose-dependent manner. Ascaridole at the dose of 20 mg/kg showed 50% ulcer protection and had a significant (P < 0.05) gastroprotective activity since it decreased the total acidity and pepsin activity. Compared to the control group, the two dosages of ascaridole showed the significant reduction (P < 0.05) in the ulcer index on Aspirin-induced ulcer. Conclusion This study provides evidence that ascaridole shows potential efficacy on the healing of gastric ulcers induced by acetic acid, Aspirin, and pylorus ligation.

Phytochemical composition and gastroprotective effect of Feijoa sellowiana Berg fruits from Sicily

Objective:To assess the fruit of Feijoa sellowiana Berg var.coolidge and gorgiona,cultured in Sicily,for its gastroprotective effect,in association with performing phytochemical evaluation.Methods:The gastroprotective effect was investigated on ethanol-induced ulcers in rats,with sucralfate as reference drug.Samples of gastric mucosae,stained by periodic acid-Shiff and haematoxylin/eosin,were observed by light microscopy.Results:By means of HPLC,vitamin E complex and polyphenol compounds were determined.identified,while δ was only in var.coolidge.In whole fruit of two varieties,catechin,eriodictyol,eriocitrin,pyrocatechol,quercetin,rutin,ellagic,gallic and syringic acid were determined.The fruit showed gastroprotective effect(ulcer index:var.coolidge=1.07,var.gorgiona=1.02).The efficacy was comparable to that of sucralfate(ulcer index 1.10).Histological examination confirmed the inhibition of ulcerogenic activity of the ethanol.Conclusions:In pulp and peel samples of both varieties of fruit α,β and γ tocopherols were and show beneficial effects on various diseases,particularly those caused by oxidative processes resulting in cell damage.The amount of polyphenols and vitamin E complex confirms the nutritional value of this fruit,grown in pedoclimatic condition very different from the origin area.Active principles of Feijoa sellowiana can play an important role in human diet and show beneficial effects on various diseases,particularly those caused by oxidative processes resulting in cell damage.The amount of polyphenols and vitamin E complex confirms the nutritional value of this fruit,grown in pedoclimatic condition very different from the origin area.