Induction Of Gastric Ulcer Research Articles

Attenuation of gastric mucosal damage by artesunate in rat: Modulation of oxidative stress and NFκB mediated signaling

A number of factors like alcohol consumption, stress, use of non steroidal anti-inflammatory drugs and acidity are well known to increase the risk of development of gastric ulcers. The present study was carried out to investigate the protective effect of artesunate against gastric injury induced in rats by oral administration of ethanol and by pylorus ligation in independent sets of experiments. The groups included in each set (n = 6 per group) were normal control, experimental control and drug treated groups: artesunate 50 and 150 mg/kg (ART 50 and ART 150) and famotidine 20 mg/kg (FAM 20). Artesunate and famotidine were given orally 1 h before induction of gastric ulceration and the macroscopic changes, median ulcer score, gastric juice parameters (volume, pH and acidity), markers of oxidative stress and inflammation (GSH, SOD, TBARS and MPO) and tissue histology were evaluated in both the models. The study was extended further for determination of tissue levels of TNF-α and expression of IL-1β, IL-6 and NFκB (p65) in ethanol induced gastric ulcer model. The results of the present study show that pretreatment with artesunate significantly decreased hemorrhagic lesions and mucosal damage with marked reduction in median ulcer score in both the models. The protective effect of artesunate was concomitant with dose-dependent normalization of gastric juice parameters, markers of oxidative stress and lipid peroxidation. The ameliorative effect of artesunate was also supported by restoration of histological architecture. Furthermore, artesunate pretreatment also alleviated the gastric mucosal inflammation as revealed by significant decrease in the tissue level of pro-inflammatory cytokine TNF-α (p < 0.01) and tissue expression of IL-1β, IL-6 and NFκB (p65). The protective effect of artesunate was found to be comparable to that of famotidine. Conclusively, artesunate afforded significant gastroprotection in rat due to its anti-oxidant and anti-inflammatory properties with transcription factor NFκB(p65) and its downstream inflammatory cascade as a plausible target for its action.

Carbon monoxide promotes gastric wound healing in mice via the protein kinase C pathway

Previous studies have shown that carbon monoxide (CO) is involved in a variety of physiological and pathophysiological processes including anti-inflammatory, anti-apoptotic and anti-oxidant responses. However, it remains unclear whether CO promotes gastric ulcer healing. In the present study, we evaluated the efficacy of CO-saturated saline in the treatment of gastric ulcers and its underlying mechanism. Acute gastric ulcers were induced in C57BL/6 male mice using acetic acid. A CO-saturated solution was prepared by bubbling 50% CO gas into saline. To investigate the effect of CO on gastric mucosal healing, CO solution was orally administrated twice a day beginning on day 3 after the induction of gastric ulcer. Mice were sacrificed on day 7 after ulcer induction. The stomach was removed, and the ulcerated lesions were measured. In vitro wound healing assays were used to determine the mechanism of action of CO in the restoration of murine gastric epithelial cells. The oral administration of CO solution accelerated the gastric ulcer healing by promoting re-epithelialization. Furthermore, the wound healing assay performed using the murine gastric epithelial cells revealed that the CO-saturated medium enhanced cell migration through the activation of protein kinase C (PKC). Based on these data, CO may represent a novel therapeutic approach for the treatment of gastric mucosal injuries.

Antiulcerogenic effect of gallic Acid in rats and its effect on oxidant and antioxidant parameters in stomach tissue.

In the present study, we investigate the antiulcerogenic effect of gallic acid against aspirin plus pyrolus ligation-induced gastric ulcer in rats. Rats were treated with gallic acid (100 and 200 mg/kg) and famotidine (20 mg/kg) for 1 week, followed by induction of gastric ulcer using the aspirin plus pyrolus ligation model. At the end of 4 h after ligation, the rats were sacrificed and ulcer index, gastric juice volume, pH and other biochemical parameter of gastric juice were evaluated. Stomachs of rats were evaluated biochemically to determine oxidant and antioxidant parameters. Pretreatment with gallic acid significantly decreased ulcer index, gastric juice volume, free and total acidity, total protein, DNA content and increased pH and carbohydrates concentration. Gallic acid at a dose of 100 and 200 mg/kg exerted 69.7 and 78.9% ulcer inhibition, respectively. The levels of superoxide dismutase, catalase, reduced glutathione, glutathione reductase, glutathione peroxidise, glucose-6-phosphate dehydrogenase were increased while reduction in myeloperoxidase and lipid peroxidation were observed in the stomach tissues of the drug treated rats. The histopathological studies further confirmed the antiulcer activity of gallic acid. We conclude that the gallic acid possesses antiulcer effect and that these occur by a mechanism that involves attenuation of offensive factors, improvement of mucosal defensive with activation of antioxidant parameters and inhibition of some toxic oxidant parameters.

The Effects of Methanolic Extract of Melissa officinalis on Experimental Gastric Ulcers in Rats.

BackgroundMelissa officinalis (MO) has potent antioxidant activity. Recent research has demonstrated the anti-ulcer properties of some medicinal plants through their antioxidant properties.ObjectivesThe aim of this study was to evaluate the effects of methanolic extracts of MO on experimental gastric ulcers in rats.Materials and MethodsMale Wistar rats (200 - 250 g) were starved for 24 hours prior to the induction of gastric ulceration by either indomethacin (48 mg/kg/oral) or water immersion restraint (WIR) stress. Experimental rats received either ranitidine (25 mg/kg) or MO extract (150, 300 and 450mg/kg) orally 2 hours prior to WIR stress or indomethacin treatment, for the evaluation of their gastroprotective effects. The control group received the same volume of saline. Gastric lesions were scored according to the surface of lesions on the ulcer index. Superoxide dismutase (SOD) and glutathione peroxidase (GPX) were determined as measures of antioxidant defense, and malondialdehyde (MDA) was determined to measure tissue oxidation.ResultsMO extract (150 and 300 mg/kg) significantly decreased the ulcer index in both the indomethacin (1.3 ± 0.09 and 1.5 ± 0.19, respectively) and WIR stress groups (1.5 ± 0.17 and 1.5 ± 0.22, respectively), as compared to the control rats (2.5 ± 0.28) (P < 0.01). MO extract (450 mg/kg) significantly reduced ulcer index readings in WIR stress rats (1.8 ± 0.31 vs. 2.4 ± 0.15 in the WIR group), however, MO extract at a dose of 450 mg/kg did not prevent indomethacin-induced gastric ulceration (2.4 ± 0.26). There was no significant difference in the ulcer index for MO extract- (150 and 300 mg/kg) and ranitidine-treated rats (P > 0.05). Also, MO extract (150 and 300 mg/kg) significantly reduced MDA serum levels (0.69 ± 0.6 µmol/L and 0.85 ± 0.24 µmol/L, respectively, vs. 4.5 ± 1.9 µmol/L in the saline group) and significantly increased antioxidants’ SOD activities (296.3 ± 146.4 U/mL and 561.4 ± 120 U/mL, respectively, vs. 190.2 ± 63.8U/mL in the control group) and GPX levels (8273 ± 3049 U/mL and 14574 ± 5012 U/mL, respectively), compared to the control (3236 ± 1699 U/mL).ConclusionsOur results showed that MO extract may have a gastroprotective effect against experimental gastric ulcers in rats. The exact mechanism has not yet been determined, but it may be due to enhancing enzymatic antioxidant defenses and inhibiting lipid peroxidation.

Gastroprotective potential of Pentahydroxy flavone isolated from Madhuca indica J. F. Gmel. leaves against acetic acid-induced ulcer in rats: The role of oxido-inflammatory and prostaglandins markers

Ethnopharmacological relevanceMadhuca indica J. F. Gmel. (Sapotaceae) has shown antioxidant, anti-inflammatory, analgesic, anti-diabetic and hepatoprotective potential. It has been traditionally used as laxative, tonic, anti-burn, anti-earthworm, wound healing and headache. Aim of the studyTo investigate the efficacy and possible mechanism of Madhuca indica J. F. Gmel. leaves methanolic extract (MI-ALC) and its isolated chloroform fraction (D3) against experimental induced gastric ulcers. Materials and methodsD3 was isolated from MI-ALC, well characterized (HPTLC, FT-IR, 1H-NMR and LC–MS) and evaluated for its gastroprotective activity by using acetic acid induced ulcer in male Wistar rats (150–200g). D3 (2.5, 5 and 10mg/kg, p.o.) were administered for the period of 14 days. At the end of treatment, rats were sacrificed to collect the stomach sample for evaluation of antioxidant (SOD, GSH, and MDA) enzyme, oxido-inflammatory (TNF-α, IL-1, iNOs) and prostaglandins (COX-II) markers by using RT-PCR. ResultsThe structure and molecular weight (MW) of the isolated compound (D3) were confirmed by 1D and 2D spectral data and characterized as 3,5,7,3′,4′-Pentahydroxy flavone with MW C15H10O7. Administration of 3,5,7,3′,4′-Pentahydroxy flavone (5 and 10mg/kg) significantly and dose-dependently inhibited (P<0.01 and P<0.001) acetic acid induced an alteration in the antioxidant enzyme. It also significantly and dose-dependently down-regulated gastric oxido-inflammatory and prostaglandins markers. Histopathological aberration induced in the stomach also attenuated by 3,5,7,3′,4′-Pentahydroxy flavone treatment. ConclusionFinding of present investigation suggests that MI-ALC possessed potent antiulcer activity due to the presence of 3,5,7,3′,4′-Pentahydroxy flavone via its oxido-inflammatory and prostaglandins modulatory potential.

Ulcer Protective and Ulcer Healing Activities of Aqueous and Methanolic Extracts of Leaves of Rumex Bequaertii De Wild (Polygonaceae) in Rats

The aqueous and methanolic extracts of Rumex bequaertii leaves were investigated for their ability to prevent and treated ulceration of the gastric mucosa in animal models.For this, adult male rats three to four months old and weighing on average 180 g were used for both tests. The extracts were tested orally at doses of 125, 250 and 500 mg/kg, on ulcerations experimentally induced by HCl/ethanol and pylorus ligation (acute ulcer) and acetic acid (chronic ulcer).These extracts showed protective and healing properties on ulcer induced models. A dose of 500 mg/kg of the two extracts inhibited ulceration induced by HCl/ethanol by 98.86 and 91.59 % respectively. With pyloric ligation, no significant variation of the volume of gastric juices, pH and gastric acidity was observed compared to the negative control rats. The aqueous extract alone at different doses presented a significant reduction of the ulceration surface resulting from chronic ulcer induced with acetic acid compared to the negative control group that received distilled water. For all three models of gastric ulcer induction used, the mass of mucus significantly increased in the groups that received the extracts. There was no significant variation in plasmatic nitric oxide (NO) concentrationand gastric supernatant of rats treated with both extracts compared to both control groups. These results reveal that the healing process of the extracts is not achieved through the NO pathway. This process could be due to increase in mucus production and thus supports its traditional use of the plant

Evaluation of Fucoidan Bioactivity as Anti Gastric Ulcers in Mice

Fucoidan is a polysaccharide compounds containing sulfate group. Fucoidan is found in brown seaweed. In this study, we assess fucoidan activity extracted from brown seaweed Sargassum crassifolium origin from Binuangeun, Banten. Fucoidan extract was tested in mice in vivo. Observations were carried out during 16 days the control (without fucoidan) and fucoidan treatment. Fucoidan were given in various concentration of 100, 200, 300, 400ppm. On the 14th day, aspirin was given to mice with pre-treated fucoidan 400ppm as gastric ulcer induction. The fucoidan extracts compositions showed: water content 3.11%, uronic acid 556ppm, 0.12ppm sulfate and 1648ppm total carbohydrate. Results from histopathology assay in mice tissue stomach showed that 100ppm of fucoidan can inhibit gastric ulcers caused by 400ppm aspirin irritation. Fucoidan was associated with an increase in the mucus layer in the gastric mucosa.

Anti-LeY antibody enhances therapeutic efficacy of celecoxib against gastric cancer by downregulation of MAPKs/COX-2 signaling pathway: correlation with clinical study.

Helicobacter pylori (H. pylori) is a major causative agent for the induction of chronic gastritis, gastric ulcer and gastric cancer. Celecoxib (COX-2 inhibitor) inhibits gastric cancer cell proliferation, but with low treatment efficacy, limiting its applications. It is important to develop a better strategy to improve the efficacy of celecoxib. Lewis Y (LeY) is a difucosylated oligosaccharide, highly expressed in 60-90% of human epithelial cancers, including gastric cancer. We previously found that H. pylori infection was associated with high level of LeY in gastric cancer. Herein, we analyzed the correlation between H. pylori and cyclo-oxygenase-2 (COX-2), LeY, gastric markers (CA724 and GRN) in gastric patient's tissue and serum samples by IHC and ELISA. Furthermore, we treated the primary gastric cancer cells with celecoxib, anti-LeY antibody or the combination, and analyzed their therapeutic efficacy on CA724, GRN and COX-2 expression by Western blot, flow cytometry and ELISA. We found that gastric cancer had significantly high expression of H. pylori, COX-2, CA724, and GRN compared to gastric ulcers and chronic gastritis (P < 0.0001). H. pylori level showed significant correlation with COX-2 (R--0.552), LeY (R--0.861), CA724 (R--0.714) and GRN (R--0.664) (P < 0.0001). Additionally, the combination therapy led to impressive inhibition of gastric cancer cell proliferation, with decreased expression of COX-2, CA724 and GRN through downregulation of MAPKs/COX-2 pathway (P < 0.01). Our findings suggest that anti-LeY antibody enhances the cancer cell proliferation inhibitory effects of celecoxib, which might be a new feasible way for gastric cancer therapy.

Antiulcerogenic activity of Carica papaya seed in rats.

The purpose of the present study was to evaluate the gastroprotective and healing effects of the methanolic extract of the seed of the papaya Carica papaya L. (MECP) in rats. Models of acute gastric ulcer induction by ethanol and indomethacin and of chronic ulcer by acetic acid were used. The gastric juice and mucus parameters were evaluated using the pylorus ligation model, and the involvement of sulfhydryl compounds (GSH) and nitric oxide in the gastroprotective effect was analyzed using the ethanol model. The toxicity was assessed through toxicity tests. No signs of toxicity were observed when the rats received a single dose of 2000mg/kg of extract. The MECP in doses of 125, 250, and 500mg/kg significantly reduced the gastric lesion with 56, 76, and 82% inhibition, respectively, and a dose of 30mg/kg lansoprazole showed 79% inhibition in the ethanol model. MECP (125, 250, 500mg/kg) and cimetidine (200mg/kg) reduced the gastric lesion in the indomethacin model, with 62, 67, 81, and 85% inhibition, respectively. The MECP (500mg/kg) and cimetidine (200mg/kg) treatments showed a reduction in ulcerative symptoms induced by acetic acid by 84 and 73%, respectively. The antiulcerogenic activity seems to involve GSH because the inhibition dropped from 72 to 13% in the presence of a GSH inhibitor. Moreover, the MECP showed systemic action, increasing the mucus production and decreasing gastric acidity. Treatments with MECP induce gastroprotection without signs of toxicity. This effect seems to involve sulfhydryl compounds, increased mucus, and reduced gastric acidity.

Terminalia catappa L.: A medicinal plant from the Caribbean pharmacopeia with anti-Helicobacter pylori and antiulcer action in experimental rodent models

Ethnopharmacological relevanceTerminalia catappa L. (Combretaceae) is a medicinal plant listed as a pharmacopeia vegetable from Caribbean to treat gastritis. The objective of this study was to evaluate the gastroprotective and healing effect of the aqueous fraction (FrAq) obtained from the leaves of Terminalia catappa and to determine the antiulcer mechanism of action in experimental rodent models and its activity to Helicobacter pylori. Material and methodsIn rodents, the FrAq was challenged by different necrotizing agents, such as absolute ethanol and ischemia–reperfusion injury. The antiulcer mechanism of action of FrAq was assessed and the healing effects of the fraction after seven and 14 days of treatment was evaluated by matrix metalloproteinase activity (MMP-2 and MMP-9). The toxicological effect of subacute treatment with FrAq during 14 days of treatment was also analyzed. The anti-Helicobacter pylori activity was determined by microdilution. The phytochemical study of the fraction was analyzed by experiments with FIA-ESI-IT-MSn (Direct Flow Analysis-ionization Electrospray Ion Trap Tandem Mass Spectrometry) and high performance liquid chromatography (HPLC) coupled to a photodiode array (PDA). ResultsOral treatment with FrAq (25mg/kg) significantly decreased the number of ulcerative lesions induced by ethanol and ischemia/reperfusion injury. The action of FrAq was mediated by the activation of defensive mucosa-protective factors, such as increases in mucus production, the nitric oxide (NO) pathway and endogenous prostaglandins. Oral treatment with FrAq for seven and 14 days significantly reduced the lesion area (80% and 37%, respectively) compared to the negative control group. Analyses of MMP-9 and MMP-2 activity from gastric mucosa confirmed the accelerated gastric healing effect of FrAq. This extract also presented considerable activity against Helicobacter pylori. The mass spectrum and MS/MS of the aqueous fraction indicates the existence of many different phenolic compounds, including punicalagin, punicalin, and gallagic acid, among others. ConclusionsWe concluded that FrAq from Terminalia catappa leaves has excellent preventive and curative effects on acute and chronic induced gastric ulcers and showed an important profile against Helicobacter pylori.

Adenosine A2A-receptor agonist polydeoxyribonucleotide promotes gastric ulcer healing in Mongolian gerbils

Polydeoxyribonucleotide (PDRN) interacts with the adenosine A2A-receptor and stimulates vascular endothelial growth factor (VEGF) expression. While it has been indicated that PDRN might accelerate wound healing, its impact on gastric ulcers (GU) is still unknown. We investigated the effects of PDRN on VEGF expression in relation to inflammation and apoptosis in GU by using Mongolian gerbils. GU was induced by injection of acetic acid into the subserosal surface of the stomach. The gerbils in the PDRN-treated groups received daily intraperitoneal injections of PDRN over 2 weeks. Reverse transcriptase-polymerase chain reaction (RT-PCR) for tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-6, as well as terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) assay, immunohistochemistry for caspase-3, and western blot for VEGF, Bax, and Bcl-2 were conducted. Acetic acid injection induced GU, and VEGF expression in the gastric mucosa was enhanced by GU. PDRN treatment decreased ulcer size and led to overexpression of VEGF in GU. Expression of TNF-α, IL-1β, and IL-6 was increased in GU, and PDRN treatment decreased the expression of these cytokines. The numbers of TUNEL-positive and caspase-3-positive cells were increased by GU, while PDRN reduced these numbers. Induction of GU enhanced the ratio of Bax to Bcl-2, while PDRN diminished this ratio. Overexpression of VEGF and inhibition of inflammation and apoptosis by PDRN may be the underlying mechanisms of PDRN action on GU healing.

Mechanisms involved in the gastroprotective activity of Celtis iguanaea (Jacq.) Sargent on gastric lesions in mice

Ethnopharmacological relevanceCeltis iguanaea (Canabaceae) is popularly known as esporão-de-galo, stands out among the medicinal plants used for treatment of gastric ulcers. In Brazil, the leaves they are used traditionally in infusion forms as an analgesic, antiasthmatic, digestive and diuretic. Aim of the studyThe present study was aimed to investigate the antiulcer mechanisms of hexane extract Celtis iguanaea leaves (HE) in several induced-gastric ulcer and characterize its chemical composition. Materials and methodsThe HE was obtained by exhaustive extraction in Soxhlet apparatus. The chemical characterization of HE was performed by Electrospray Fourier transform ion cyclotron mass spectrometry (ESI FT-ICR MS) analysis. Mice were used for the evaluation of the gastroprotective activity. HE was analyzed in the HCl/ethanol, hypothermic restraint stress ulcer and acetic acid. In the investigation of the gastroprotective mechanisms of HE, were performed the amount of adhered gastric mucus, participation of the α2-adrenoceptor, nitric oxide (NO) and prostaglandins (PGs) using the HCl/ethanol-induced gastric mucosa lesion model. ResultsESI FT-ICR MS analysis of HE suggest the presence of compounds as lipids, sterol lipids, steroids glycosides and polyphenol glycosides. The oral administration of HE at doses of 100mg/kg or 200mg/kg was able to protect the gastric mucosa against HCl/ethanol (10mL/kg p.o.), and HE at dose of 100mg/kg protected against hypothermic-restraint stress and acetic -induced gastric lesions. The pretreatment with Yoimbine (2mg/kg, s.c.), an antagonist α2-adrenergic, L-NAME (20mg/kg, s.c.), an inhibitor of nitric oxide synthesis or indomethacin (10mg/kg, s.c.), an inhibitor of prostaglandin production, reversed the gastroprotective activity of HE (100mg/kg, p.o.). ConclusionsOur results suggest that the Celtis iguanaea HE exhibits gastroprotective activity in different gastric ulcer models. The mechanism of gastroprotective effect of Celtis iguanaea HE suggests the participation of mucus as well as the involvement of α2-adrenergic receptors, NO and prostaglandins. The hydroxyl-linolenic acid, linoleic acids and conjugated oxo-linoleic acids are among the phytoconstituents that were identified in the Celtis iguanaea HE.

The effects of aqueous extract of Aloe vera leaves on the gastric acid secretion and brain and intestinal water content following acetic acid- induced gastric ulcer in male rats.

Gut-brain axis (GBA) is very important in creation and modulation of gastrointestinal problems. Aloe vera gel has gastroprotective properties. The purpose of this study was to evaluate the effect of aqueous extract of Aloe vera leaves on the gastric acid secretion and brain and intestinal water content following acetic acid gastric ulcer induction. Gastric ulcer was induced by injection of 20% acetic acid into the subserosal layer in male rats. Rats were randomly assigned into three groups: intact group, gastric ulcer group and Aloe vera group (treatment with Aloe vera following gastric ulcer induction). The acid levels and brain and intestinal water content of each sample were measured eight days after the gastric ulcer induction. Gastric acid levels were significantly decreased in Aloe vera group when compared with gastric ulcer group (p<0.05). However, there were no differences in acid output between gastric ulcer and Aloe vera groups with intact group. After Aloe vera administration, the amount of brain water content had no difference with intact and gastric ulcer groups (p<0.05). The duodenal water content in Aloe vera group was significantly reduced compared with intact group (p<0.05) but gastric ulcer group had no significant difference with intact and Aloe vera group. The administration of Aloe vera has an inhibitory effect on the gastric acid output.

Helicobacter Pylori Induced Gastric Inflammation, Ulcer, and Cancer: A Pathogenesis Perspective

Helicobacter pylori infection induces gastric inflammation, ulcer, and cancer. H. pylori infection is coordinated in a cascade manner that helps it to colonize in the host. Colonization of bacterium starts by adapting itself to the harsh acidic environment in the stomach. H. pylori has the necessary machinery to neutralise the pH of its surroundings. It also has the ability to sense the pH of its surroundings and move towards the less acidic region. H. pylori’s next hurdle is gastric mucosal barrier in the stomach and it has the capability to overcome this gastric mucosal barrier. Once the gastric mucosal barrier is weakened, pathogen uses different adhesion molecules to adhere to the epithelial lining of the stomach. Pathogen then establishes interaction with the host using several toxins that indirectly leads to development of inflammation or gastritis. Prolonged inflammation damages epithelial cells leading to ulcers in the stomach. Genetic changes in the host cell due to H. pylori infection leads to development of gastric cancer. The present paper reviews in detail H. pylori induced gastritis, gastric ulcers and gastric cancer.

Anti-ulcerogenic properties of Albuca setosa

Albuca setosa is a medicinal plant used by Xhosa tribe in the rural area of South Africa for the treatment of wounds, articulation problems, rheumatoid arthritis and digestive disorders. This study aimed to evaluate the healing effect of A. setosa on experimental induced gastric ulcer. The antiulcerogenic effects of A. setosa were investigated in male Wistar rats. Gastric ulcer was induced per os using indomethacin (50 mg/kg) and ethanol (2 ml/animal). The ulceration lesion index was calculated for each one of the ulcerated stomach; the macroscopic and histomorphology evaluation were made. In indomethacin-induced gastric ulcers, oral administration of A. setosa significantly inhibited (P<0.01) gastric ulcer formation by 82 and 83% at the dose of 100 and 200 mg/kg, respectively. In ethanolinduced gastric ulcers, A. setosa significantly inhibited (P<0.05) gastric ulcer formation by 39 and 35% at the dose of 100 and 200 mg/kg, respectively. Macroscopic evaluation of ulcerated stomachs of A. setosa treated groups showed a reduced area of gastric lesion, with moderate disruption of the gastric epithelium as well as the mucosa stromal cell. The results obtained in this study suggest that the A. setosa possesses some anti-ulcerogenic properties, which may support evidence for its traditional use.

Healing effects of Musa sapientum var. paradisiaca in diabetic rats with co-occurring gastric ulcer: cytokines and growth factor by PCR amplification

BackgroundThe present study evaluates the effects of extract of Musa sapientum fruit (MSE) on ulcer index, blood glucose level and gastric mucosal cytokines, TNF-α and IL-1β and growth factor, TGF-α (affected in diabetes and chronic ulcer) in acetic acid (AA)-induced gastric ulcer (GU) in diabetic (DR) rat.MethodsMSE (100 mg/kg, oral), omeprazole (OMZ, 2.0 mg/kg, oral), insulin (INS, 4 U/kg, sc) or pentoxyphylline (PTX, 10 mg/kg, oral) were given once daily for 10 days in 14 days post-streptozotocin (60 mg/kg, intraperitoneal)-induced diabetic rats while, the normal/diabetic rats received CMC for the same period after induction of GU with AA. Ulcer index was calculated based upon the product of length and width (mm2/rat) of ulcers while, TNF-α, IL-1β and TGF-α were estimated in the gastric mucosal homogenate from the intact/ulcer region. Phytochemical screening and HPTLC analysis of MSE was done following standard procedures.ResultsAn increase in ulcer index, TNF-α and IL-1β were observed in normal (NR)-AA rat compared to NR-normal saline rat, which were further increased in DR-AA rat while, treatments of DR-AA rat with MSE, OMZ, INS and PTX reversed them, more so with MSE and PTX. Significant increase in TGF-α was found in NR-AA rat which did not increase further in DR-AA rat. MSE and PTX tended to increase while, OMZ and INS showed little or no effect on TGF-α in AA-DR rat. Phytochemical screening of MSE showed the presence of saponins, flavonoids, glycosides, steroids and alkaloids and HPTLC analysis indicated the presence of eight active compounds.ConclusionMSE showed antidiabetic and better ulcer healing effects compared with OMZ (antiulcer) or INS (antidiabetic) in diabetic rat and could be more effective in diabetes with concurrent gastric ulcer.

Gastroprotective effects of Corchorus olitorius leaf extract against ethanol-induced gastric mucosal hemorrhagic lesions in rats.

Background and AimCorchorus olitorius is a medicinal plant traditionally utilized as an antifertility, anti-convulsive, and purgative agent. This study aimed to evaluate the gastroprotective effect of an ethanolic extract of C. olitorius against ethanol-induced gastric ulcers in adult Sprague Dawley rats.MethodsThe rats were divided into seven groups according to their pretreatment: an untreated control group, an ulcer control group, a reference control group (20 mg/kg omeprazole), and four experimental groups (50, 100, 200, or 400 mg/kg of extract). Carboxymethyl cellulose was the vehicle for the agents. Prior to the induction of gastric ulcers with absolute ethanol, the rats in each group were pretreated orally. An hour later, the rats were sacrificed, and gastric tissues were collected to evaluate the ulcers and to measure enzymatic activity. The tissues were subjected to histological and immunohistochemical evaluations.ResultsCompared with the extensive mucosal damage in the ulcer control group, gross evaluation revealed a marked protection of the gastric mucosa in the experimental groups, with significantly preserved gastric wall mucus. In these groups, superoxide dismutase and malondialdehyde levels were significantly increased (P < 0.05) and reduced (P < 0.05), respectively. In addition to the histologic analyses (HE and periodic acid-Schiff staining), immunohistochemistry confirmed the protection through the upregulation of Hsp70 and the downregulation of Bax proteins. The gastroprotection of the experimental groups was comparable to that of the reference control medicine omeprazole.ConclusionsOur study reports the gastroprotective property of an ethanolic extract of C. olitorius against ethanol-induced gastric mucosal hemorrhagic lesions in rats.

Suppression of alkylating agent induced cell transformation and gastric ulceration by low-dose alkylating agent pretreatment

Exposure to mild stress by chemicals and radiation causes DNA damage and leads to acquired stress resistance. Although the linear no-threshold (LNT) model of safety assessment assumes risk from any dose, evidence from radiological research demonstrates a conflicting hormetic phenomenon known as the hormesis effect. However, the mechanisms underlying radiation hormesis have not yet been clarified, and little is known about the effects of low doses of chemical carcinogens. We analyzed the efficacy of pretreatment with low doses of the alkylating agent N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) on the subsequent induction of cell transformation and gastric ulceration by high-dose MNNG. We used an in vitro Balb/3T3 A31-1-1 cell transformation test and monitored the formation of gastric ulcers in 5-week-old male ICR mice that were administered MNNG in drinking water. The treatment concentrations of MNNG were determined by the cell survival rate and past reports. For low-dose in vitro and in vivo experiments, MNNG was used at 0.028μM, and 2.8μg/mL, respectively. The frequency of cell transformation induced by 10μm MNNG was decreased by low-dose MNNG pretreatment to levels similar to that of spontaneous transformation. In addition, reactive oxygen species (ROS) and mutation frequencies induced by 10μm MNNG were decreased by low-dose MNNG pretreatment. Importantly, low-dose MNNG pretreatment had no effect on cell proliferation. In vivo studies showed that the number of gastric ulcers induced by 1mg/mL MNNG decreased after low-dose MNNG pretreatment. These data indicate that low-dose pretreatment with carcinogens may play a beneficial role in the prevention of chemical toxicity under specified conditions.

Extraction of the volatile oil from Carum carvi of Tunisia and Lithuania by supercritical carbon dioxide: chemical composition and antiulcerogenic activity

This study investigates whether the essential oil prepared from Carum carvi seeds exhibits antiulcerogenic activity. Its volatile oil was obtained by supercritical fluid extraction (SFE) and by hydrodistillation. The essential oils were analysed by GC–MS to monitor their composition. The chemical analysis revealed that the essential oils extracted under SFE conditions had high carvone and limonene contents. The antiulcerogenic activity was evaluated by the HCl/ethanol method, which causes injury to the gastric mucosa. Three treated groups received the essential oil (100–300 mg/kg). The reference group received omeprazole (30 mg/kg) and the control group received NaCl. After 30 min, all groups were treated with HCl/EtOH for gastric ulcer induction. The results show C. carvi essential oil enhanced a significant inhibition of 47%, 81% and 88%, respectively, for three doses of essential oil used, which was similar to that induced by omeprazole (95%) (p < 0.005).

Atividade antiulcerogênica do extrato aquoso da Bryophyllum pinnatum (Lam.) Kurz

Bryophyllum pinnatum (Lam.) Kurz pertence a família Crassulaceae e é conhecida vulgarmente como coirama, folha-da-fortuna, ou folha-do-ar, sendo usada popularmente como antifúngico, no tratamento da hipertensão, em úlceras e em inflamações. O presente estudo objetivou analisar a atividade antiulcerogênica do extrato aquoso das folhas de Bryophyllum pinnatum (Lam.) Kurz em modelo de úlcera gástrica induzida por indometacina em Rattus norvegicus, machos (150 a 250 g) com idade de 70 dias. Os animais receberam por via oral: água, extrato aquoso de Bryophyllum pinnatum (Lam.) Kurz (1 e 2 g Kg-1 ) ou ranitidina (60 mg Kg-1 ), fármaco com ação gastroprotetora conhecida que atua bloqueando os receptores de histamina H2. Após uma hora dos tratamentos, todos animais receberam indometacina via intraperitoneal. Os resultados demonstraram que o extrato aquoso da Bryophyllum pinnatum (Lam.) Kurz possui ação gastroprotetora; na dose de 1 g Kg-1 inibiu 45,49% o índice de ulceração induzido pela indometacina, e, na dose de 2 g Kg-1, inibiu 49,50%. Sugere-se o envolvimento de vários mecanismos na ação gastroprotetora dessa planta e não somente uma possível participação das prostaglandinas nesse efeito. Estudos futuros com diferentes modelos de indução de úlcera gástrica tornam-se necessários para melhor avaliar a atividade antiulcerogênica do extrato aquoso de Bryophyllum pinnatum (Lam.) Kurz.