Healing Of Chronic Gastric Ulcers Research Articles

Physiological healing of chronic gastric ulcer is not impaired by the hydrogen sulphide (H2S)-releasing derivative of acetylsalicylic acid (ATB-340): functional and proteomic approaches.

Gastric ulcers affect approx. 10% of population. Non-steroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid (ASA) predispose to or impair the physiologically complex healing ofpre-existing ulcers. Since H2S is an endogenous cytoprotective molecule, we hypothesized that new H2S-releasing ASA-derivative (ATB-340) could overcome pathological impact of NSAIDs on GI regeneration.Clinically translational gastric ulcers were induced in Wistar rats using state-of-the-art microsurgical model employing serosal application of acetic acid. This was followed by 9 days long i.g. daily treatment with vehicle, ATB-340 (6-24mg/kg) or equimolar ASA doses (4-14mg/kg). Ulcer area was assessed macro- and microscopically. Prostaglandin (PG)E2 levels,indicating pharmacological activity of NSAIDsand 8-hydroxyguanozine content,reflecting nucleic acids oxidation in serum/gastric mucosa, were determined by ELISA. Qualitative and/or quantitative pathway-specific alterations at the ulcer margin were evaluated using real-time PCR and mass spectrometry-based proteomics.ASA, unlike ATB-340, dose-dependently delayed/impaired gastric tissue recovery, deregulating 310 proteins at the ulcer margin, including Ras signalling, wound healing or apoptosis regulators. ATB-340 maintained NSAIDs-specific cyclooxygenase-inhibiting capacity on systemic and GI level but in time-dependent manner. High dose of ATB-340 (24mg/kg daily), but not ASA, decreased nucleic acids oxidation and upregulated anti-oxidative/anti-inflammatory heme oxygenase-1, 24-dehydrocholesterol reductase or suppressor of cytokine signalling (SOCS3) at the ulcer margin.Thus, ASA impairs the physiological healing of pre-existing gastric ulcers, inducing the extensive molecularly functional and proteomic alterations at the wound margin. H2S-releasing ATB-340 maintains the target activity of NSAIDs with limited impact on gastric PGE2 signalling and physiological GI regeneration, enhancing anti-inflammatory and anti-oxidative response, andproviding the pharmacological advantage.

Phenolic profile and chronic gastric ulcer healing effects of Cameroonian propolis

BackgroundGastric ulcers continue to affect millions of people worldwide, with reported cases of fatalities and the diagnosis, prevention and treatment constitute a burden on the patients especially in case of chronic ulcers which are difficult to treat. Natural medicines such as propolis provide suitable therapeutic alternatives in the treatment and curation of ulcers. ObjectiveThis work focused on the evaluation of the phenolic profile and healing effect of Cameroonian propolis on gastric ulcers in rats. MethodsIdentification and quantification of phenolic compounds in the propolis extract was done using HPLC-DAD. Chronic gastric ulcers were induced using ethanol (70%; 1 mL/200 g p.o.)/indomethacin (1 mg/kg p.o.), and “unhealed” gastric ulcerations were induced using acetic acid (30%)/indomethacin (1mg/kg p.o.). The animals were administered with the vehicle (tween 20, 1 mL/100 g p.o.), propolis extract (200, 400 and 600 mg/kg p.o.) or sucralfate (50 mg/kg p.o.), once daily for ten to fourteen days. At the end of each treatment period, the animals were sacrificed and ulcer indices, gastric mucus weight, histological and oxidative stress parameters were assessed. ResultsEight phenolic compounds were identified and quantified and most abundant were Caffeic acid (45.31±0.25 µg/g), Chrysin (37.65±0.17 µg/g) and p-Hydroxy benzoic acid (34.14±0.21 µg/g). The treatment of ulcerated rats (chronic and unhealed gastric ulcer models) with propolis extract at 200, 400 and 600 mg/kg resulted in reduction of ulcer index compared to negative controls in both models. Histological observation of stomach tissues showed that treatment with propolis extract led to a dose-dependent normalization of the mucosa. There was a significant increase (P < 0.5; P < 0.01 and P < 0.001) in mucus weight that accompanied the healing of the ulcers. Furthermore, doses of 200, 400 and 600 mg/kg of the propolis extract induced an increase in the amounts of SOD, catalase, nitrite and GSH while MDA concentrations decreased in both models. ConclusionThe healing effect of propolis extract is due to the stimulation of mucus production followed by an improvement of in vivo antioxidant status. These results support the use of propolis in the development of new pharmacological strategies for the management of peptic ulcers disease.

Neuropeptide W facilitates chronic gastric ulcer healing by the regulation of cyclooxygenase and NF-κB signaling pathways

AimsPutative beneficial effects of neuropeptide W (NPW) in the early phase of gastric ulcer healing process and the involvement of cyclooxygenase (COX) enzymes were investigated in an acetic acid-induced gastric ulcer model.Main methodsIn anesthetized male Sprague–Dawley rats, acetic acid was applied surgically on the serosa and then a COX-inhibitor (COX-2-selective NS-398, COX-1-selective ketorolac, or non-selective indomethacin; 2 mg/kg/day, 3 mg/kg/day or 5 mg/kg/day; respectively) or saline was injected intraperitoneally. One h after ulcer induction, omeprazole (20 mg/kg/day), NPW (0.1 μg/kg/day) or saline was intraperitoneally administered. Injections of NPW, COX-inhibitors, omeprazole or saline were continued for the following 2 days until rats were decapitated at the end of the third day.Key findingsNPW treatment depressed gastric prostaglandin (PG) I2 level, but not PGE2 level. Similar to omeprazole, NPW treatment significantly reduced gastric and serum tumor necrosis factor-alpha and interleukin-1 beta levels and depressed the upregulation of nuclear factor kappa B (NF-κB) and COX-2 expressions due to ulcer. In parallel with the histopathological findings, treatment with NPW suppressed ulcer-induced increases in myeloperoxidase activity and malondialdehyde level and replenished glutathione level. However, the inhibitory effect of NPW on myeloperoxidase activity and NPW-induced increase in glutathione were not observed in the presence of COX-1 inhibitor ketorolac or the non-selective COX-inhibitor indomethacin.SignificanceIn conclusion, NPW facilitated the healing of gastric injury in rats via the inhibition of pro-inflammatory cytokine production, oxidative stress and neutrophil infiltration as well as the downregulation of COX-2 protein and NF-κB gene expressions.

Evaluation of Acetic Acid-Induced Chronic Gastric Ulcer Healing by Propionyl-L-Carnitine Administration.

The aim of our study was to investigate the healing effect of propionyl-L-carnitine (PLC) on chronic gastric ulcers and its underlying mechanisms. This study included rats with gastric ulcers induced by applying serosal glacial acetic acid. These rats were then given either saline (vehicle) or PLC at doses of 60 and 120 mg/kg, administered orally 3 days after ulcer induction for 14 consecutive days. Our study found that treatment with PLC resulted in a reduction of the gastric ulcer area, a faster rate of ulcer healing, and stimulated mucosal restoration. Additionally, the treatment with PLC reduced the number of Iba-1+ M1 macrophages while increasing the number of galectin-3+ M2 macrophages, as well as desmin+ microvessels, and α-SMA+ myofibroblasts in the gastric ulcer bed. The mRNA expression of COX-2, eNOS, TGF-β1, VEGFA, and EGF in the ulcerated gastric mucosa was greater in the PLC-treated groups compared with the vehicle-treated rats. In conclusion, these findings suggest that PLC treatment may accelerate gastric ulcer healing by stimulating mucosal reconstruction, macrophage polarization, angiogenesis, and fibroblast proliferation, as well as fibroblast-myofibroblast transition. This process is associated with the upregulation of TGF-β1, VEGFA, and EGF, as well as modulation of the cyclooxygenase/nitric oxide synthase systems.

Chronic Gastric Ulcer Healing Actions of the Aqueous Extracts of Staple Plant Foods of the North-West, Adamawa, and West Regions of Cameroon.

This study is aimed at establishing phenolic compound profile and assessing the possible antiulcer activities of aqueous extracts of some staple plant foods from the West and North-West regions of Cameroon against chronic gastric ulcer models in rats. Phenolic constituents of extracts were evaluated using HPLC-DAD. Aqueous extracts of Corchorus olitorius, Solanum nigrum, Vigna unguiculata, Triumfetta pentandra, "nkui" spices, and "yellow soup" spices were tested at two doses (200 and 400 mg/kg). After treatments, animals were sacrificed, healing percentage and antioxidant status (catalase, superoxide dismutase, and glutathione peroxidase) were evaluated, and histological examination of gastric mucosa was realized. HPLC-DAD revealed that p-hydroxybenzoic and protocatechuic acids were the phenolic compound present in all extracts. Oral administration of extracts (200 and 400 mg/kg) significantly reduced ulcer surface value and significantly increased mucus production compared to the control groups (p < 0.05). Histological study supported the observed healing activity of different extracts characterized by a reduced inflammatory response. Moreover, administration of aqueous extracts increased the activity of antioxidant enzymes. This study revealed that aqueous extracts of Solanum nigrum, Corchorus olitorius, Vigna unguiculata, Triumfetta pentandra, "yellow soup" spices, and "nkui" spices possess healing antiulcer effects against models of gastric ulcers. The antiulcer mechanisms involved may include increase of gastric mucus production and improvement of the antioxidant activity of gastric tissue. These activities may be due to the phenolic compounds identified in the extracts, especially p-hydroxybenzoic and protocatechuic acids present in all extracts and with known antioxidant, cytoprotective, and healing properties. However, all the diets may promote the healing process of chronic ulcers caused by excessive alcohol consumption/stress.

Ethanolic Stem Bark Extract of Boswellia dalzielli H Promotes the Healing of Acetic Acid Induced Chronic Gastric Ulcer by Down-Regulation of Tumor Necrosis Factor (TNF) -Αlpha in Wistar Albino Rats

The present study determines the effects of the ethanolic stem bark extract of Boswellia dalzielii H on gastric homogenate and serum levels of TNF-α and vascular endothelial growth factor (VEGF), during the healing of chronic gastric ulcer induced by acetic acid in Wistar albino rats. Round and deep chronic gastric ulcers were induced by a high concentration of acetic acid in Wistar albino rats. 75 rats with gastric ulcers were randomly assigned to five treatment groups (2-5). Rats in group 1 had no gastric ulcer and were administered with vehicle 5ml/kg. Rats in group 2, negative control had gastric ulcers and were treated with vehicle 5ml/kg. Rats in group 3 were treated with ranitidine (50mg/kg) while rats in groups 4, 5, and 6 were treated daily with 100, 200, and 400mg/kg of ethanolic stem bark extract of Boswellia dalzielli H respectively. Treatment in all the groups was by intragastric administration. Five rats from groups (2-6) were euthanized on days 3, 7, and 9 along with the control group (1). Blood was collected, serum prepared, and assayed for TNFα and VEGF using ELISA. The stomach of each animal was evaluated for gastric ulcer, assessed for histopathologic changes, and preparation of gastric tissue homogenates. Intragastric administration of graded doses of ethanolic stem bark extract of Boswellia dalzielli H and ranitidine (50mg/kg) respectively, down-regulated serum and gastric tissue levels of TNF–α significantly (p&lt;0.05), up-regulated VEGF significantly (p&lt;0.05), and increased gastric ulcer healing rate in a significant manner (p&lt;0.05). The increase was time and Dose and time dependent manner when compared to control. Attenuation of TNFα and up-regulation of VEGF by graded intragastric administration of the ethanolic stem bark extract of Boswellia dalzielli promotes the healing of chronic gastric ulcer induced by acetic acid in Wister albino rats.

In-vitro Antacid Properties of Cameroonian Clay (MY41g) and its Potential Use in Anti-ulcer Triple Therapy Regimen Formulated with Eremomastax speciosa Extract

Aims: The antisecretory, antibacterial on Helicobacter, and antacid properties of Eremomastax speciosa (E. speciosa) and MY41g clay respectively, led us to evaluate the potential use of this clay in the anti-ulcer tri-therapy formulated with Eremomastax speciosa.&#x0D; Place and Duration of Study: Department of Animal Biology &amp; Physiology (Animal Physiology Laboratory), Faculty of Science, University of Yaoundé I, between August 2020 and February 2021.  &#x0D; Materials and Methods: In vitro antacid were evaluated by studying: Fordtran's method, and the influence of temperature on the pH values. In vivo activity was studied on chronic gastric ulcers induced by injection of 0.05 ml of acetic acid (30%) into the stomach wall. Rats were treated daily for 10 days after ulcer induction with a combination of E. speciosa and MY41g (ESMY) ; (ESMY 100+250 and 200+250 mg/kg). The model of "unhealed" gastric ulcers was also used: from day 5 to day 18 of experimentation, rats were given ESMY orally concomitantly with indomethacin (1 mg/kg/day) subcutaneously. Ulcer index, percentage of healing, mucus secretion, gastric acidity, histological, hematological, and oxidative stress parameters were evaluated.&#x0D; Results: ESMY showed good neutralizing capacity in vitro in Fordtran’s method. Treatment with ESMY accelerated the spontaneous healing of chronic gastric ulcers (93.82-96.14%). However, administration of indomethacin did not induce significant variations in the percentage of healing (90.73-94.60%). For both ulcer models performed, ulcer healing was accompanied by a significant (P = 0.001) increase in mucus mass at 200/250 mg/kg. ESMY increased antioxidant activity, decreased gastric acidity, lipid peroxidation, and maintained hematological balance.&#x0D; Conclusion: In addition to its buffering properties, the healing mechanism of ESMY includes reduced gastric acidity, enhanced mucus production, re-epithelialization of gastric mucosa, improvement of hematological and antioxidant status. ESMY can be used in traditional medicine, as a therapeutic regimen against gastric ulcers.  

In Vivo Curative and Antacid Effects of Cameroonian Clay (MY41g) on Chronic and “Unhealed" Gastric Ulcers in Rats

This study evaluated the in vivo curative and antacid effects of MY41g clay on chronic and “unhealed" gastric ulcers in rats. Chronic gastric ulcers were induced by injecting 0.05 mL of acetic acid (30%) into the stomach wall. From day 5-14 after induction of ulcers, rats were treated daily with MY41g clay (125 and 250 mg/kg). For “Unhealed" gastric ulcers, from day 5-18 rats received MY41g clay orally concomitantly with indomethacin (1 mg/kg/day) subcutaneously. The ulcer index, percentage of healing, mucus secretion, histological parameters, oxidative stress parameters and gastric acidity were assessed. Treatment with clay solution for 10 days resulted in accelerated spontaneous healing of chronic gastric ulcers (83.69-90.2%). However, indomethacin administration did not induce significant variations in the percentage of healing (89.23-91.66%) in rats. For both ulcer models performed, ulcer healing was accompanied by a significant increase (p&lt;0.001) of mucus secretion at the highest dose. Clay increased concentrations of antioxidant enzymes and decreased gastric acidity and lipid peroxidation. Administration of clay accelerated the spontaneous healing of both induction models. The mode of action of the clay could involve increased gastric mucus production, gastric mucosal re-epithelialization, improved antioxidant status and gastric acid neutralization. MY41g clay can be used as antacids in the ulcer treatment regime.

Cochlospermum regium (Mart. ex Schrank) Pilg.: Evaluation of chemical profile, gastroprotective activity and mechanism of action of hydroethanolic extract of its xylopodium in acute and chronic experimental models

Ethnopharmacological relevanceCochlospermum regium (Bixaceae) is a native shrub of Brazil and its xylopodium (infusion/decoction) is being used for the treatment of gastritis, ulcers, arthritis, intestinal infections, gynaecological infections, skin diseases, among others. The aim of the present study was to evaluate the gastroprotective/antiulcer activity and the mechanism of action of hydroethanolic extract of C. regium xylopodium (HECr), using in vitro and in vivo models. Additionally, phytochemical constituents were identified by high-performance liquid chromatography (HPLC). Materials and methodsC. regium xylopodium was macerated with ethanol/water to obtain the HECr. The phytochemical characterisation was carried out by HPLC. The antiulcer efficacy of HECr (25, 100 and 400 mg/kg, p.o.) was evaluated using acute acidified ethanol (HCl/EtOH), piroxicam and water immersion-induced experimental ulcer models. Chronic gastric ulcer healing activity of HECr was evaluated through acetic acid (99.8%) – induced model. Histological analysis and myeloperoxidase (MPO), glutathione (GSH), catalase (CAT) activities were also evaluated in chronic ulcer induced gastric tissues. The plausible mode of action of the HECr was assessed by estimation of gastric wall mucus production and the role of gastric secretion in pylorus ligature. The animals were also pre-treated with various inhibitors which includes indomethacin (10 mg/kg, p.o.) a selective inhibitor of cyclooxygenase, L-NAME (10 mg/kg, i.p.), an inhibitor of nitric oxide synthase, glibenclamide, a ATP-sensitive potassium channels (K+ATP) blocker (5 mg/kg, p.o.) or yohimbine (2 mg/kg, i.p.), an α2-adrenergic receptor antagonist. In vitro, Helicobacter pylori action was done by broth microdilution method. ResultsThe HPLC analysis data revealed the presence of gallic acid, rutin, myricetin, morin and kaempferol. HECr promoted protective effect against acute ulcers induced by HCl/EtOH with inhibitions of 47.52% (p < 0.01) and 62.69% (p < 0.001) at 100 and 400 mg/kg, and in piroxicam by 34.11% (p < 0.05), 49.14% (p < 0.01) and 61.34% (p < 0.001), at 25, 100 or 400 mg/kg, respectively, and in water restraint stress by 78.26% inhibition, p < 0.001, at the dose of 400 mg/kg when compared to the vehicle control group respectively. In the chronic gastric ulcer model, HECr (25, 100 and 400 mg/kg p.o.) significantly (p < 0.001) decreased the injured area by 58.80%, 77.87% and 71.10% respectively. Histological examination indicated that oral treatment of HECr promoted healing of gastric lesions by regenerating gastric mucosa layer with less inflammatory cells. HECr augmented the GSH, CAT activities and reduced MPO level. The pre-treatment with HECr increased the gastric wall mucus production. It also significantly altered the gastric secretion parameters by causing the reduction in the gastric juice volume, elevated the pH level and reduced the total acidity at all doses tested when compared with the vehicle group. HECr at the most active dose (100 mg/kg) reversed completely the reduction of PGs, NO production, closure of K+ATP- channels and α2-adrenoreceptor blockage – induced damages. In microdilution assay, the HECr showed good anti-Helicobacter pylori effect with MIC = 100 µg/mL. ConclusionThe HECr presented preventive and curative effects in the experimental gastric ulcer models, besides good anti-Helicobacter pylori activity, which supports the traditional medicinal use of the xylopodium of this plant for gastrointestinal diseases. The underlying mechanisms of this antiulcerogenic/antiulcer action involve, at least, augmentation of mucus production, inhibition of gastric secretion, stimulation of PGs and NO synthesis. And that it involves activation of K+ATP channels and α-2-adrenergic receptors, in addition to an antioxidant activity, probably due to the presence of gallic acid and flavonoids in HECr.

Exendin-4, a glucagon-like peptide-1 analogue accelerates healing of chronic gastric ulcer in diabetic rats

BackgroundDiabetes mellitus is an independent risk factor for impaired healing of peptic ulcers, and there are currently no supplementary therapeutics other than the standard antipeptic medicine to improve the ulcer healing in diabetes. This study examined the potential pleiotropic effect of a glucagon-like peptide (Glp)-1 analogue exendin (Ex)-4 on the regeneration of gastric ulcer in streptozotocin-induced diabetic rats.Methods and resultsChronic ulcer was created in rat stomach by submucosal injection of acetic acid and peri-ulcer tissues were analyzed 7 days after operation. Ulcer wound healing was impaired in diabetic rats with suppressed tissue expression of eNOS and enhanced levels of pro-inflammatory reactions. Treatment with intraperitoneal injection of Ex4 (0.5 μg/kg/d) significantly reduced the area of gastric ulcer without changing blood glucose level. Ex-4 restored the expression of pro-angiogenic factors, and attenuated the generation of regional inflammation and superoxide anions. The improvement of ulcer healing was associated with increased expression of MMP-2 and formation of granulation tissue in the peri-ulcer area.ConclusionAdministration of Ex4 may induce pro-angiogenic, anti-inflammatory and anti-oxidative reactions in the peri-ulcer tissue of diabetic rats that eventually enhances tissue granulation and closure of ulcerative wounds. Our results support the potential clinical application of Glp-1 analogues as supplementary hypoglycemic agents in the antipeptic ulcer medication in diabetes.

Hydroethanolic extract of Baccharis trimera promotes gastroprotection and healing of acute and chronic gastric ulcers induced by ethanol and acetic acid.

Ethanol is a psychoactive substance highly consumed around the world whose health problems include gastric lesions. Baccharis trimera is used in folk medicine for the treatment of gastrointestinal disorders. However, few studies have evaluated its biological and toxic effects. To validate the popular use of B. trimera and elucidate its possible antiulcerogenic and cytotoxic mechanisms, a hydroethanolic extract of B. trimera (HEBT) was evaluated in models of gastric lesions. Rats and mice were used to evaluate the protective and antiulcerogenic effects of HEBT on gastric lesions induced by ethanol, acetic acid, and chronic ethanol consumption. The effects of HEBT were also evaluated in a pylorus ligature model and on gastrointestinal motility. The LD50 of HEBT in mice was additionally estimated. HEBT was analyzed by nuclear magnetic resonance, and a high-performance liquid chromatography fingerprint analysis was performed. Oral HEBT administration significantly reduced the lesion area and the oxidative stress induced by acute and chronic ethanol consumption. However, HEBT did not protect against gastric wall mucus depletion and did not alter gastric secretory volume, pH, or total acidity in the pylorus ligature model. Histologically, HEBT accelerated the healing of chronic gastric ulcers in rats, reflected by contractions of the ulcer base. Flavonoids and caffeoylquinic acids were detected in HEBT, which likely contributed to the therapeutic efficacy of HEBT, preventing or reversing ethanol- and acetic acid-induced ulcers, respectively. HEBT antiulcerogenic activity may be partially attributable to the inhibition of free radical generation and subsequent prevention of lipid peroxidation. Our results indicate that HEBT has both gastroprotective and curative activity in animal models, with no toxicity.

EFFECTIVENESS OF PLATELET-ENRICHED PLASMA IN TREATMENT OF CHRONIC GASTRIC ULCERS

The article presents the results of clinical study of the effect of platelet-enriched plasma in healing of chronic gastric ulcers. It has been demonstrated that a single local stimulation of reparatory processes of the stomach wall by endoscopic injection of platelet-enriched plasma allows significantly (p&lt;0,01, tStudent test) to reduce the area of large ulcers, and to achieve 100% healing of ulcers of a medium size.

Aqueous Extract of Enantia chlorantha (Annonaceae) Prevents the Delay in Chronic Gastric Ulcer Healing Caused by Indomethacin in Rats

Aims: To investigate the ability of Enantia chlorantha aqueous extract to heal acetic acid-induced chronic gastric ulcers and to prevent the delay in chronic ulcer healing induced by indomethacin. Study Design: Random allocation of male rats to groups of five rats each. Place and Duration of Study: Department of Animal Biology and Physiology, Animal Physiology Laboratory (Gastroenterology Research Unit) University of Yaounde 1 and Department of Biomedical Sciences (Pathology Unit), University of Buea between January and April 2015. Methodology: Gastric ulcers were produced 5 days after submucosal injection of 30% acetic acid (0.05 ml) at the lesser curvature of rat stomachs corpus. The extract (250 and 500 mg/kg) was administered p.o. during 10 days. Ulcer healing was delayed by indomethacin administered s.c. at 1 mg/kg once daily for 2 weeks from 5 days after the acid injection. Extract or sucralfate were administered concomitantly. Mucus secretion and oxidative stress parameters (superoxide dismutase (SOD), malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT)) were measured, and macroscopic and histological assessment of ulcer healing was done. Results: Ulcer healing rates were 82.7% and 88.6% for the 250 and 500 mg/kg doses of extract following 10 day treatment of acetic acid-induced ulcers vs 55.7% and 85.2% for spontaneous healing and Ranititine, respectively. Spontaneous healing (60.9%) was significantly (P<0.01) delayed by indomethacin (22.5% healing rate). Co-administration of extract (250-500 mg/kg) or sucralfate (100 mg/ kg) significantly (P<.001) inhibited the adverse effect of indomethacin, raising healing rates to 76.7%, 82.2% and 85.8%, respectively. Indomethacin significantly depressed gastric mucus production (39.79 mg) but extract and sucralfate restored values to 40.08-55.75 mg and 70.06 mg, respectively. Indomethacin raised MDA levels and decreased antioxidant enzyme levels. These effects were counteracted by E. chlorantha extract. Microscopy showed advanced re-epithelialisation with recovery of ulcer craters due to extract. Conclusion: E. chlorantha accelerates the spontaneous healing of acetic acid-induced chronic gastric ulcers, and prevents the delay in chronic gastric ulcer healing caused by indomethacin. The healing-promoting effect of the extract could be due not only to stimulation of gastric mucus secretion but also to enhanced re-epithelialisation and inhibition of enhanced lipid peroxidation in the ulcerated gastric tissue.

Ethanolic extract of roots from Arctium lappa L. accelerates the healing of acetic acid-induced gastric ulcer in rats: Involvement of the antioxidant system

We evaluate the curative efficacy of the ethanolic extract (EET) of roots from Arctium lappa (bardana) in healing of chronic gastric ulcers induced by 80% acetic acid in rats and additionally studies the possible mechanisms underlying this action.Oral administration of EET (1, 3, 10 and 30mg/kg) reduced the gastric lesion area in 29.2%, 41.4%, 59.3% and 38.5%, respectively, and at 10mg/kg promoted significant regeneration of the gastric mucosa, which was confirmed by proliferating cell nuclear antigen immunohistochemistry. EET (10mg/kg) treatment did not increase the gastric mucus content but restored the superoxide dismutase activity, prevented the reduction of glutathione levels, reduced lipid hydroperoxides levels, inhibited the myeloperoxidase activity and reduced the microvascular permeability. In addition, EET reduced the free radical generation and increased scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals in vitro. Furthermore, intraduodenal EET (10 and 30mg/kg) decreased volume and acidity of gastric secretion. Total phenolic compounds were high in EET (Folin–Ciocalteau assay) and the analysis by liquid chromatography-mass spectrometry revealed that the main compounds present in EET were a serie of hydroxycinnamoylquinic acid isomers. In conclusion, these data reveal that EET promotes regeneration of damaged gastric mucosa, probably through its antisecretory and antioxidative mechanisms.

Chronic gastric ulceration causes matrix metalloproteinases-9 and -3 augmentation: alleviation by melatonin.

Matrix metalloproteinases (MMPs) are a family of zinc-dependent enzymes capable of degradation of extracellular matrix (ECM) and key player in various inflammatory diseases. We investigated the regulation of MMPs in chronic gastric ulceration in mice. We generated chronic gastric ulcers in mice by indomethacin and examined the activity and expression of MMP-9 and -3 in stomach. Melatonin (N-acetyl-5-methoxytryptamine) treatment has also been applied to mice to characterize the changes in expression and activities of MMPs in gastric tissues. We observed significant upregulation of MMP-9 and -3 expressions and activities in stomach with increasing doses and duration of indomethacin that corroborated with increased activity of activator protein (AP)-1. Substantial damage in gastric epithelial layer was found during chronic ulceration. Melatonin suppressed MMP-9 and -3 expressions and activities during prevention and healing of chronic gastric ulcers. It also suppressed protein oxidation, lipid peroxidation and antioxidant enzymes. Additionally, expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-8 was significantly high in ulcerated stomachs while melatonin treatment blocked them to control level. We found elevated phosphorylation of extracellular-regulated kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK) during chronic gastric ulceration, which were significantly reversed by melatonin. Moreover, expression of NF-κB, c-fos and c-jun were inhibited by melatonin resulting down regulation of MMP-9 and -3 expressions. In summary, oxidative stress is preceded by chronic inflammation that enhances the expression of MMP-9 and -3, while melatonin arrests both of them via reduction of AP-1 activity during protection of ulcer.

Administration of obestatin accelerates the healing of chronic gastric ulcers in rats

SummaryBackgroundPrevious studies have shown that administration of obestatin exhibits a protective effect in the pancreas, attenuating the development of acute pancreatitis. The aim of the present study was to investigate the influence of obestatin administration on the healing of chronic gastric ulcers.Material/MethodsChronic gastric ulcers were induced in rats by 100% acetic acid applied to the serosal surface of the gastric wall. Obestatin was given twice a day intraperitoneally at the dose of 4, 8 or 16 nmol/kg/dose for 6 days. Six days after induction of ulcers, rats were anesthetized and the stomach was exposed for measurement of gastric blood flow and ulcer area. Biopsy samples from the gastric mucosa were taken for determination of mucosal DNA synthesis and for measurement of gastric expression of mRNA for interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α).ResultsInduction of gastric ulcers alone increased mucosal blood flow and tissue expression of mRNA for TNF-α and IL-1β, whereas gastric mucosal DNA synthesis was reduced. In rats with gastric ulcers, administration of obestatin increased gastric mucosal blood flow, accelerated the healing rate of these ulcers and partly reversed the gastric ulcer-induced reduction in gastric mucosal DNA synthesis. These results were associated with a reduction in gastric mucosal expression of pro-inflammatory IL-1β and TNF-α.ConclusionsTreatment with obestatin increases gastric mucosal blood flow and cell proliferation, leading to acceleration of healing of gastric ulcers. These effects are associated with a reduction in mucosal expression of pro-inflammatory IL-1β and TNF-α.

Delayed healing of chronic gastric ulcer after Helicobacter pylori infection in mice.

It has been suggested that there is a close relationship between Helicobacter pylori and the onset or recurrence of gastroduodenal disease. The aim of this study was to examine the effect of H. pylori on the healing of chronic gastric ulcers induced in mice. H. pylori administered to nude mice delayed the healing of experimental acetic acid-induced gastric ulcers. Histological examination showed the occurrence of high densities of H. pylori on the surface of epithelial cells and in the ulcerated area. Repeated administration of amoxicillin (10 mgkg(-1) daily for 5 days) eradicated H. pylori and increased the rate of healing of gastric ulcers in H. pylori-infected mice, but metronidazole, which also eradicated the organisms, did not significantly affect the rate of healing. In conclusion, H. pylori-infection delayed the healing of gastric ulcers induced by the serosal application of acetic acid in mice, possibly by aggravation or prolongation of the mucosal inflammation. Amoxicillin eradicated H. pylori and promoted gastric ulcer healing in mice infected with H. pylori.

Yogurt ContainingLactobacillus gasseriOLL 2716 (LG21 yogurt) Accelerated the Healing of Acetic Acid-Induced Gastric Ulcer in Rats

We have reported that LG21 yogurt containing Lactobacillus gasseri OLL 2716 (LG21 yogurt) inhibits the formation of HCl-induced acute gastric lesions through the generation of prostaglandin E₂. This study aimed to determine the role of viable Lactobacillus in the healing of acetic acid-induced chronic gastric ulcer. LG21 yogurt or γ-ray radiated LG21 yogurt was administered orally twice a day for 10 d at a dose of 5 ml/kg. LG21 yogurt significantly accelerated the healing of the ulcer, but γ-ray radiated LG21 yogurt did not. However, both yogurts significantly inhibited HCl-induced gastric erosive lesions and enhanced the generation of gastric mucosal prostaglandin E₂. From the above results, it was found that viable bacteria are needed to accelerate the healing of chronic gastric ulcer, but not to inhibit gastric lesions.

883 Helicobacter pylori-Derived HP (2-20) Stimulates Gastric Mucosal Recovery From Stress-Induced Gastric Lesions and Accelerates the Healing of Chronic Gastric Ulcers

883 Helicobacter pylori-Derived HP (2-20) Stimulates Gastric Mucosal Recovery From Stress-Induced Gastric Lesions and Accelerates the Healing of Chronic Gastric Ulcers

Involvement of Orexigenic Peptides in the Mechanism of Gastric Mucosal Integrity and Healing of Chronic Gastric Ulcers

Orexigenic peptides are group of endocrine hormones exerting a pleiotropic influence on many physiological functions including regulation of the feeding behaviour and energy expenditure, release of growth hormone (GH) and inotropic effects on the heart. Some of these peptides such as ghrelin, originally identified in the gastric mucosa, has been involved not only in control of food intake and growth hormone release but also exerts the immunomodulatory and anti-inflammatory properties. This review summarizes the recent attempts to prove the concept that orexigenic peptides such as ghrelin, orexin-A and obestatin besides playing an important role in the mechanism of food intake, exhibit a potent gastroprotective action against the formation of acute gastric mucosal injury induced by various ulcerogens. This protective effect depends upon vagal activity and hyperemia mediated by NOS/NO and COX/PG systems and CGRP released from sensory afferent nerves. In addition, the appetite peptides such as ghrelin and orexin-A are implicated in the mechanism of the healing of preexisting gastric ulcers due to an activation of specific GHS-R1a and OX-R1 receptors and PG/COX system.