Development Of Gastric Ulcers Research Articles

A Comprehensive Review on In-Situ Gel Drug Delivery System

Over the past ten years, in situ gelling drug delivery methods have attracted a lot of attention. Prior to injection, they are in a sol-state, and they can gel when exposed to a variety of endogenous stimuli, including temperature rise, pH changes, and the presence of ions. Such to accomplish the injection of a local or systemic medication, systems may be delivered by a variety of can also be employed effectively as carriers for nano- and microparticles that carry drugs. Natural or artificial or in conjunction with semi-artificial polymer exhibiting in situ gelling behaviour. For the development of such systems, coupling with mucoadhesive polymers is highly sought in order to prolong the duration spent at the site of action or absorption. Nasal drug administration is a superior option than oral and parental routes because of the high permeability of the nasal epithelium, rapid drug absorption, avoidance of hepatic first pass metabolism, improved bioavailability of the medication, and fewer adverse effects. adverse local and systemic effects, minimal dosage is required, Patient compliance has increased, direct distribution to the CNS and systemic circulation is available, and self-medication. The development of gastric ulcers can be prevented. Recent evidence indicates that many medications have greater oral bioavailability than nasal bioavailability. So, the focus of this review is on nasal drugs. Administration, various nasal architecture and physiology characteristics, the method of nasal absorption, and benefits, Evaluations of in situ gels' composition, use, and advantages and disadvantages.
 Keywords: Nasal formulation, sustained drug administration, mucoadhesive drug delivery system, and in-situ nasal gelation.

Repurposing dimethyl fumarate for gastric ulcer and ulcerative colitis: Evidence of local efficacy without systemic side effect

Ulcerative colitis and gastric ulcer are ulcers of gastrointestinal track, especially associated with elevated oxidative stress and inflammation. Dimethyl fumarate (DMF) is used for the treatment of multiple sclerosis and psoriasis and is considered useful in a variety of conditions associated with inflammation. We have investigated the effect of oral DMF (1, 10, 25, 50, 100, 200 mg/kg) in ethanol-induced gastric ulcers in rats. The effect of oral (15, 30, and 60 mg/kg) and intracecal (15 mg/kg) DMF was also investigated in dextran sulfate sodium (DSS)-induced colitis in mice. Treatment of DMF by oral route prevented the development of ethanol-induced gastric ulcers by decreasing oxidative stress in a dose-related manner. Oral and intracecal administration of DMF attenuated body weight loss, increase in disease activity score, colon length shortening, colon weight loss, inflammation and fibrosis, and decreased myeloperoxidase activity. Oral and intracecal DMF prevented a decrease in hemoglobin and suppressed oxidative stress, and also decreased MCP-1, IL-1ß, and IL-6 levels in the inflamed colon. Unlike oral DMF, intracecal DMF treatment did not reduce spleen weight. The effect of intracecal DMF was similar to the highest tested dose of oral DMF (60 mg/kg). These results demonstrated that intracecal DMF suppresses inflammation and oxidative stress in ethanol and DSS-induced colitis without alteration of spleen weight. This suggests that the localized DMF administration could be beneficial approach of treating gastrointestinal ulcers.

Assessment of Gastric Acid Anti-Secretory Effects of Fraction Extracts of Piper guineense Leaf on Histamine-Induced Gastric Ulcer in Wistar Rats

Despite many etiological factors, gastric acid secretion is assumed to play a central role in the development of gastric ulcer. Blockade of gastric acid secretion therefore, seems to be the key therapeutic objective of gastric ulcer disease. Available acid-blocking/anti-secretory drugs used in the management of gastric ulcer are associated with high cost, unwanted side effects and treatment relapse. Extracts from plants can be useful and may serve as an alternative to conventional drugs in gastric ulcer management. This work was aimed at assessing the gastric acid anti-secretory effects of fractionated ethanol extract of Piper guineense leaf on histamine-induced ulcer in Wistar rats. This was conducted by administering orally, 400mg/kg of fraction extracts obtained by fractionation of ethanol-extracted residue, to fifty six adult Wistar rats randomized into eight groups (n=7) of animals followed by induction of ulcer with 40mg/kg histamine, orally. The effects of the plant extracts on histamine-induced ulcer, gastric pH and gastric volume were ascertained. From the results, all the extracts significantly (p<0.05) produced ulcer inhibition, increased gastric pH and reduced gastric volume. This study concludes that extracts of Piper guineense leaf possess antiulcer effects, which may occur via histamine-2-receptor blockade and/or anti-secretory mediated activities. Keywords: Gastric acid, Fraction extracts, Histamine, Anti­secretory, Piper guineense

Evaluation of the prevalence of stomach ulcers in slaughtered pigs in a Swiss ­abattoir

The development of gastric ulcers in pigs has various reasons. In Switzerland, the last survey on the prevalence of gastric ulcers and possible risk factors was performed in 2005. We aimed to reassess gastric ulcers prevalence today, in 2021. A total of 1005 stomachs from fattening pigs from 136 batches and around 87 herds were evaluated at a Swiss abattoir. The Pars oesophagea of the stomach was scored from 0=healthy to 10=severe ulceration and strictures. Scores were compared between pigs produced under the labels «Integrierte Produktion Schweiz» (IPS, n=242 stomachs, 18 farms) and «Qualitätsmanagement-Schweizerfleisch» (QM, n=649, 58 farms) and others (n=114). The results showed a prevalence of 27,2 % mild mucosal changes (Scores 1-3), 14,9 % moderate mucosal changes (Scores 4-6) and 19,1 % severe mucosal changes (Scores 7-10). Only 38,8 % of the stomachs were rated 0 and thus considered healthy. Compared to the results from 2005, there is no difference concerning the lowest scores (0-2) and the highest scores (9-10). However, there was a shift from the medium scores (3-4) to higher scores (5-8). Stomach scores turned out to be herd specific. There were differences (p < 0,01) between labels, indicating that IPS pigs had less affected stomachs. Stomachs that were empty at slaughter showed higher scores (p < 0,001). The mean carcass weight of the pigs in the slaughter groups was negatively correlated (p < 0,05) to their median stomach score. Confiscations were not related to stomach scores. The results suggest that pig stomach health has not improved since 2005. The differences between labels seem to have resulted from different regulations prescribing a minimum particle size of enrichment material in IPS. The reasons for gastric ulcer development, including those on the individual herd within label, still have to be further clarified in order to allow targeted countermeasures. Given apparent farm-specificity, scoring of a limited number of stomachs per herd during the slaughter process could facilitate the establishment of a feedback scheme.

Gastroprotective Effects of Aqueous Extract of Hibiscus sabdariffa Calyx on Nonsteroidal Anti-Inflammatory Drug-Induced Gastric Ulcer in Wistar Rats

Background: Gastric ulcer is the most common gastrointestinal disorder associated with high morbidity and significant mortality and has been described as the plaque of the 19th and 20th centuries. The most conventional antiulcer drugs are largely ineffective and associated with disease recurrence, thus identifying natural products with potential antiulcer properties is essential. Objective: The aim of this study was to investigate the potential protective effects of aqueous extract of Hibiscus sabdariffa calyx (AEHSC) against nonsteroidal anti-inflammatory drug (NSAID)-induced gastric ulcer. Materials and Methods: Thirty male rats weighing 170–230 g were randomized into five groups as: ulcerated control group (distilled water, n = 6), experimental extract groups 1, 2, and 3 (AEHSC 100 mg/kg, 200 mg/kg, and 400 mg/kg, respectively, n = 6 each), and positive control group (ranitidine 20 mg/kg, n = 6); ulcer was induced using oral indomethacin 40 mg/kg, 30 min after all interventions. Rats were sacrificed 5 h after ulcer induction. Blood samples were taken for serum hydroxyproline determination; gastric tissues were also visualized (ulcer index (UI) and percentage of ulcer protection), and later stained and viewed under a microscope. Results: There was a significant (P &lt; 0.05) reduction in UI in treated rats compared with control. The percentage of ulcer protection was also significantly increased (P &lt; 0.05). Histological slides also indicated increased epithelial mucus secretion in stomach tissues of rat treated with AEHSC. Conclusions: AEHSC may be potentially beneficial in protection against the development of NSAID-induced gastric ulcers.

Manifestação de úlceras gástricas em equinos aplicados na segurança pública

ABSTRACT We evaluated 28 horses from a squad applied in public safety in Paraná (Brazil), in order to check the incidence of gastric ulcers and its correlation with mounted policing activity, considering the initial and maintenance training to which such animals are submitted. Horses were divided in two groups, one named control with 14 individuals, used in policing community activities, and the 14 others named as target group, these were used in restoration and maintenance of public order. Both groups have differentiated maintenance training protocols, and all had been evaluated for fecal occult blood, clinical evaluation, gastroscopy and histopathological. There were no significant changes that proved the development of gastric ulcers in horses used in public safety due to initial and maintenance training, and the main factor for prevention was the diversified diet with emphasis in hayed alfalfa.

Therapeutic Effects of Vitamin E in Gastric Stress Ulcers and Obesity in Rats

Stress – related disturbances are classified among the health problems that have global interest, especially which are related to gastrointestinal system. The consequent oxidative stress is confirmed to be responsible for the development of gastric mucosal ulcers and necrosis. That is accompanied with the release of different inflammatory mediators. On the other hand, the ratio of obesity is gradually increasing in the world. It impairs the quality of life because of its associated serious complications. Vitamin E is a fat-soluble, free radicals scavenger antioxidant. It has anti-inflammatory and cell membrane-stabilizing properties. Besides, it has anti – obesity effects. The present study highlights the potential therapeutic effects of vitamin E in the treatment of stress-induced gastric ulcers in rats. Stomach injury was induced in fasted rats by cold- restraint stress (CRS) method. Vitamin E was administered orally at a dose of 100 mg/kg for 7 consecutive days. Rats were sacrificed on the 8th day. Assessment of the stomach injury was by studying body weight changes, macroscopic examinations, histological study, and determination of oxidative stress markers (MDA stomach content and SOD enzyme activity). Vitamin E administration alleviated the stomach injury degree, and caused a remarkable body weight decrease, with a statistical significance in comparison with the stressed group. Vitamin exerted good effects in reducing body weight, and healing of stress-induced gastric ulcers in rats.

Correlation between Endoscopic Morphology and Bleeding of Gastric Ulcer.

Objective To improve the safety and reliability of gastric ulcer treatment, the emergence of digestive endoscopy technology in recent years has become a conventional method for the diagnosis of peptic ulcer bleeding. Endoscopic characteristics can judge the severity of patients more accurately and comprehensively, provide a basis for follow-up treatment, and judge the prognosis. Methods 298 patients with a suspected gastric ulcer who underwent laryngeal gastroduodenal endoscopy and confirmed gastroduodenal ulcer in our hospital in recent half a year were randomly selected. Olympus cv-170 electronic gastroscope machine was used to carry out gastroscopy for patients with gastric ulcers, analyze, and judge the number of bleeding cases in different stages of treatment, such as lesion type, lesion location, patient age, and gender. The statistics of bleeding cycle and bleeding volume, prognosis recovery, and the correlation of different risk levels were analyzed. Results After examination and diagnosis, the patients were followed up for one year. According to the number of bleeding cases, bleeding cycle, and bleeding volume of patients with different ulcer locations in the acute stage, healing stage, and scar stage, the distribution of bleeding cases of different ulcer locations in different stages was roughly the same, and there was no significant difference. The proportion of bleeding cases in the acute stage was the highest, while the proportion in the healing stage was the lowest. The number of bleeding cases, bleeding cycle, bleeding volume, and related symptoms in patients with gastric ulcers during the treatment were significantly correlated with those in the acute stage, healing stage, and scar stage. There was no significant difference in the distribution of bleeding in one year among different stages of ulcer in the same age group, however, the bleeding in one year would be more serious with the increase of age in different age groups. Gender differences have a great impact on the bleeding of the ulcer within one year. It usually shows that the bleeding of ulcers in males is more serious than that in females. Conclusion The location and pathological development of gastric ulcers can be found in time through gastroscopy, and the status of gastroscopy can be analyzed. Most gastric ulcers are acute bleeding. The amount of bleeding has little correlation with the stage of gastric ulcer, and it is related to the location of bleeding. The older the age, the greater the amount of bleeding, and the amount of bleeding in men is greater than that in women. In the treatment of gastric ulcers, gastroscopy, as a doctor's examination and treatment method, effectively improves the safety and reliability of clinical treatment of gastric ulcer bleeding and reduces the adverse risk.

Clinical Biomarkers and Use of Herbal Products in Gastric Injury

An ulcer in the stomach is a common digestive system ailment. Gastric ulcers are more likely to develop if one drinks alcohol regularly. Despite the extensive availability of treatment options, there are just a few preventative regimes. In animal trials, herbal remedies have been found to prevent the formation of ethanol-induced stomach ulcers. Histamine receptor 2 antagonists have a similar or higher ability to inhibit the formation of ethanol-induced stomach ulcers to herbal treatments. There are less adverse effects associated with herbal remedies. PubMed, Google Scholar, and Web of Science databases were searched using keywords such as "gastric ulcer," "herbal medicines," and "ethanol-induced gastric injury." The search was performed up to May 15, 2021. Only articles published in English were used in this review. For those who are more susceptible to develop stomach ulcers, certain herbal combinations may be an effective option to prevent the development of gastric ulcers, based on their methods of action and the pathogenesis of gastric ulcers. Dates, pomegranate seeds, and bitter melon are all examples of herbal compounds that are safe and can be ingested. Those who regularly use alcohol may want to consider using these substances as an alternative method of preventing stomach ulcers. Anti- Helicobactor pylori herbal components such as Mitrella kentia, citrus lemon, and Cratoxylum arborescens (Vahl) Blume can be used by Helicobacter pylori-positive individuals to avoid the creation of ethanol-induced stomach ulcers.

Chemical, biological, and pharmacological evaluation of the aqueous extract of Ilex paraguariensis, St. Hill. (Aquifoliaceae)

This study aimed to quantify the total phenolic and flavonoid contents in the aqueous extract of Ilex paraguariensis (EIP) and investigate its antioxidant, antimicrobial, antiulcerogenic, and antidepressant properties with concomitant verification of its effects on relevant biochemical parameters using in vivo models. EIP has in its composition 236.28 ± 11.83 mg GAE/g of total phenolics and 44.07 ± 5.56 mg QE/g of total flavonoids, corroborating its antioxidant activity. Antimicrobial assays against gram-positive (Staphylococcus aureus and Enterococcus faecalis) and gram-negative bacteria (Escherichia coli e Pseudomonas aeruginosa) showed a promising activity of EIP. The EIP administered at 500 and 1000 mg/kg doses prevented the development of gastric ulcers induced in rats following immobilization at 4 °C, however, in the ethanol-induced ulcers no significant effects were observed up to a dose of 1000 mg/kg. Gastric secretion and total acidity index in pylorus-ligated rats were reduced after treatment with EIP, and the pH did not change significantly compared to the control in the tested model. Administration of EIP to mice (250, 500, and 1000 mg/kg) significantly altered the barbiturate-induced sleep time and results of the tail suspension and forced swim test. Repeated doses of EIP did not significantly alter the evaluated biochemical markers (blood glucose, urea, creatinine, triglycerides, and total cholesterol). The results indicate that EIP may relieve gastrointestinal disorders by reducing acid secretion and decreasing immobility time in mice, suggesting an antidepressant effect. Notably, administration of multiple doses of EIP was considered preliminarily safe.

Helicobacter pylori in gastric cancer: Features of infection and their correlations with long-term results of treatment.

BACKGROUND Helicobacter pylori (H. pylori) is a spiral-shaped bacterium responsible for the development of chronic gastritis, gastric ulcer, gastric cancer (GC), and MALT-lymphoma of the stomach. H. pylori can be present in the gastric mucosa (GM) in both spiral and coccoid forms. However, it is not known whether the severity of GM contamination by various vegetative forms of H. pylori is associated with clinical and morphological characteristics and long-term results of GC treatment. AIMTo establish the features of H. pylori infection in patients with GC and their correlations with clinical and morphological characteristics of diseases and long-term results of treatment.METHODSOf 109 patients with GC were included in a prospective cohort study. H. pylori in the GM and tumor was determined by rapid urease test and by immunohistochemically using the antibody to H. pylori. The results obtained were compared with the clinical and morphological characteristics and prognosis of GC. Statistical analysis was performed using the Statistica 10.0 software. RESULTS H. pylori was detected in the adjacent to the tumor GM in 84.5% of cases, of which a high degree of contamination was noted in 50.4% of the samples. Coccoid forms of H. pylori were detected in 93.4% of infected patients, and only coccoid-in 68.9%. It was found that a high degree of GM contamination by the coccoid forms of H. pylori was observed significantly more often in diffuse type of GC (P = 0.024), in poorly differentiated GC (P = 0.011), in stage T3-4 (P = 0.04) and in N1 (P = 0.011). In cases of moderate and marked concentrations of H. pylori in GM, a decrease in 10-year relapse free and overall survival from 55.6% to 26.3% was observed (P = 0.02 and P = 0.07, respectively). The relationship between the severity of the GM contamination by the spiral-shaped forms of H. pylori and the clinical and morphological characteristics and prognosis of GC was not revealed.CONCLUSIONThe data obtained indicates that H. pylori may be associated not only with induction but also with the progression of GC.

SR-5, the specific ratio of Korean multi-herbal formula: An evaluation of antiulcerogenic effects on experimentally induced gastric ulcers in mice.

PurposePreviously, we demonstrated that the specific ratio of Korean multi-herbal formula (SR-5) exhibits hepatoprotective properties against ethanol-induced hepatic damage in rats. Chronic and excessive alcohol consumption is a major etiological factor involved in gastric disease and ulcer development induced by the inflammatory response and oxidative stress.MethodsThe present study evaluated the gastroprotective effects of SR-5 (100, 150, and 200 mg/kg) against hydrochloride acid/ethanol (HCl/EtOH)-induced and indomethacin/hydrochloride acid (INDO/HCl)-induced gastritis in a mouse model and the mechanisms involved.ResultsAll the tested doses of SR-5 significantly inhibited gastric lesions in the HCl/EtOH-induced ulcer model mice. Similarly, all the tested doses of SR-5 significantly inhibited gastric lesions in the INDO/HCl-induced ulcer model mice. Furthermore, mice pretreated with SR-5 had significantly increased gastric levels of enzymatic and nonenzymatic antioxidants, namely, catalase (CAT) and glutathione (GSH), with concomitant reductions in malondialdehyde (MDA) and reactive oxygen species (ROS) levels compared with those in the HCl/EtOH or INDO/HCl group. SR-5 suppressed the expression of nuclear factor-kappa B (NF-κB)/p65, inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), and cyclooxygenase-2 (COX-2) to their normal values.ConclusionThese findings are the first to demonstrate the powerful protective effect of SR-5 against gastric injury development and provide hope for clinical application.

Agarwood Alcohol Extract Protects against Gastric Ulcer by Inhibiting Oxidation and Inflammation.

Background Agarwood has been used for centuries, especially for treatment of gastrointestinal diseases. Earlier studies of our laboratory suggested that agarwood alcohol extracts (AAEs) provided gastric mucosal protection. This study aims to investigate the ameliorative effect of AAEs on ethanol-induced gastric ulcers and its mechanism. Methods Mice were given agarwood induced by the whole-tree agarwood-inducing technique alcohol extract (WTAAE, 0.71, 1.42, and 2.84 g/kg), wild agarwood induced by axe wounds alcohol extract (WAAE, 2.84 g/kg), and burning-chisel-drilling agarwood alcohol extract (FBAAE, 2.84 g/kg) orally, respectively. After 7 days' pretreatment with AAEs, the gastric ulcers were induced by absolute ethanol. The ulcer index, gastric histopathology, biochemical parameters, and inflammatory proteins were evaluated. Results Pharmacological results showed AAEs (1.42 and 2.84 g/kg) reduced the gastric occurrence and ulcer inhibition rates up to more than 60%. AAEs decreased the level of nitric oxide (NO) and increased glutathione (GSH) and superoxide dismutase (SOD) levels. Besides, AAEs decreased the levels of interleukin-1β (IL-1β) and interleukin-6 (IL-6), but the interleukin-10 (IL-10) was upregulated. The expressions of nuclear factor kappa B (NF-κB) and phosphorylated protein 38 (p-P38) were inhibited. The effect of WTAAE was better than that of FBAAE and similar to that of WAAE at the dose of 2.84 g/kg. Conclusions These results demonstrate that agarwood alleviates the occurrence and development of gastric ulcers via inhibiting oxidation and inflammation.

Association of the functionally significant polymorphisms of the MMP9 gene with H. pylori-positive gastric ulcer in the Caucasian population of Central Russia.

Background and purposeThe study analyzed the association of functionally significant polymorphisms of matrix metalloproteinases (MMPs) genes with the development of gastric ulcer (GU) in Caucasians from Central Russia.MethodsThe 781 participants, including 434 patients with GU (196 Helicobacter pylori (H. pylori)-positive and 238 H. pylori-negative) and 347 controls (all H. pylori-negative) were recruited for the study. Ten SNPs of the MMP1 (rs1799750), MMP2 (rs243865), MMP3 (rs679620), MMP8 (rs1940475), and MMP9 (rs3918242, rs3918249, rs3787268, rs17576, rs17577, and rs2250889) genes were considered for association with GU using multiple logistic regression. The SNPs associated with GU and loci linked (r2≥0.8) to them were analyzed in silico for their functional assignments.ResultsThe SNPs of the MMP9 gene were associated with H. pylori-positive GU: alleles C of rs3918249 (OR = 2.02, pperm = 0.008) and A of rs3787268 (OR = 1.60–1.82, pperm ≤ 0.016), and eight haplotypes of all studied MMP9 gene SNPs (OR = 1.85–2.04, pperm ≤ 0.016) increased risk for H. pylori-positive GU. None of the analyzed SNPs was independently associated with GU and H. pylori-negative GU. Two haplotypes of the MMP9 gene (contributed by rs3918242, rs3918249, rs17576, and rs3787268) increased risk for GU (OR = 1.62–1.65, pperm ≤ 0.006). Six loci of the MMP9 gene, which are associated with H. pylori-positive GU, and 65 SNPs linked to them manifest significant epigenetic effects, have pronounced eQTL (17 genes) and sQTL (6 genes) values.ConclusionSNPs of the MMP9 were associated with H. pylori-positive GU but not with H. pylori-negative GU in Caucasians of Central Russia.

Gastroprotective effect of cirsilineol against hydrochloric acid/ethanol-induced gastric ulcer in rats.

This study was designed to evaluate the gastroprotective activity of cirsilineol in hydrochloric acid (HCl)/ethanol-induced gastric ulcer model. Cirsilineol was administered at the doses of 20 and 40 mg/kg in HCl/ethanol-induced rats. The gastroprotective ability was verified by determining the ulcer score, total acidity, hemoglobin, inflammatory cytokines, lipid peroxides, and enzymatic antioxidants superoxide dismutase (SOD) and catalase (CAT) in gastric tissue and serum biochemical analysis. The results showed a favorable increase in the hemoglobin level, antioxidant enzymes (SOD and CAT), restored electrochemical balance (carbon dioxide & anion gap) while a noticeable decrease in ulcer index, total acidity, lipid peroxides, inflammatory cytokines (interleukin-1 beta [IL-1β], IL-6, and tumor necrosis factor alpha) in rats treated with the cirsilineol. The serum biochemical analysis on liver markers (alkaline phosphatases, alanine aminotransferase, and aspartate aminotransferase), kidney markers (urea, creatinine, albumin, globulin, total protein), and lipid profile (triglyceride, high-density lipoprotein, total cholesterol) were attenuated by cirsilineol treatment in rats. Histopathology showed enhanced gastric protection and preserved the integrity of gastric mucosa upon cirsilineol administration. These results ultimately suggest that cirsilineol has gastroprotective effects that prevent the development of gastric ulcer.

Protective effects of andrographolide against diclofenac-induced gastric damage

The use diclofenac in pain management is limited by the development of gastric ulcers. Andrographolide is a clinically approved medicinal plant extract that has been found to possess among others, a gastro protective effect and may therefore be useful in protecting against damaging effects of diclofenac. The research study aimed at determining the gastro-protective effect of andrographolide in the presence of diclofenac. Two rodent models of gastro-protection were used in this study. In the mouse pyloric ligation model, effect of andrographolide alone and in combination with diclofenac on secretion of gastric contents was determined. In the acute gastritis model, effects of andrographolide on diclofenac induced ulcers in rats was evaluated. Haematoxylin and Eosin (H&E) stain was used in histopathological examination in the acute gastritis model. All statistical analysis was done using one way analysis of variance.In the mouse pyloric ligation model, diclofenac treatment significantly lowered the pH (1.46 ± 0.1453 compared to ligated controls 3.30 ± 0.0577, p < 0.05), and co-administration of diclofenac with andrographolide raised it significantly (pH of 4.80 ±0.3512 in combination compared to diclofenac only treated groups with pH of 1.46 ± 0.1453, p < 0.001). The standard anti-ulcer drug, esomeprazole also produced a similar elevation in pH (3.87 ± 0.2848 for esomeprazole compared to diclofenac only treated groups with pH of 1.46 ±0.1453, p < 0.01). Esomeprazole and andrographolide also reduced the mucosal damaging effects of diclofenac in the acute gastritis model in rats with a reduction in the number of ulcers produced (esomeprazole 50 mg/kg, 1.0 ± 0.6000, p < 0.0001 and andrographolide 100 mg kg/kg, 2.0 ± 0.6000, p < 0.001 compared to vehicle treated groups, 10.0 ± 1.095). Histopathological examination showed reduction in damaging effects of diclofenac after andrographolide and esomeprazole administration.Results show andrographolide possesses gastro-protective effect in the presence of diclofenac.

Design, synthesis, and evaluation of peptide-imidazo[1,2-a]pyrazine bioconjugates as potential bivalent inhibitors of the VirB11 ATPase HP0525.

Helicobacter pylori (H. pylori) infections have been implicated in the development of gastric ulcers and various cancers: however, the success of current therapies is compromised by rising antibiotic resistance. The virulence and pathogenicity of H. pylori is mediated by the type IV secretion system (T4SS), a multiprotein macromolecular nanomachine that transfers toxic bacterial factors and plasmid DNA between bacterial cells, thus contributing to the spread of antibiotic resistance. A key component of the T4SS is the VirB11 ATPase HP0525, which is a hexameric protein assembly. We have previously reported the design and synthesis of a series of novel 8-amino imidazo[1,2-a]pyrazine derivatives as inhibitors of HP0525. In order to improve their selectivity, and potentially develop these compounds as tools for probing the assembly of the HP0525 hexamer, we have explored the design and synthesis of potential bivalent inhibitors. We used the structural details of the subunit-subunit interactions within the HP0525 hexamer to design peptide recognition moieties of the subunit interface. Different methods (cross metathesis, click chemistry, and cysteine-malemide) for bioconjugation to selected 8-amino imidazo[1,2-a]pyrazines were explored, as well as peptides spanning larger or smaller regions of the interface. The IC50 values of the resulting linker-8-amino imidazo[1,2-a]pyrazine derivatives, and the bivalent inhibitors, were related to docking studies with the HP0525 crystal structure and to molecular dynamics simulations of the peptide recognition moieties.

AdipoRon, an Orally Active, Synthetic Agonist of AdipoR1 and AdipoR2 Receptors Has Gastroprotective Effect in Experimentally Induced Gastric Ulcers in Mice

Introduction: Adiponectin is a hormone secreted by adipocytes, which exhibits insulin-sensitizing and anti-inflammatory properties and acts through adiponectin receptors: AdipoR1 and AdipoR2. The aim of the study was to evaluate whether activation of adiponectin receptors AdipoR1 and AdipoR2 with an orally active agonist AdipoRon has gastroprotective effect and to investigate the possible underlying mechanism. Methods: We used two well-established mouse models of gastric ulcer (GU) induced by oral administration of EtOH (80% solution in water) or diclofenac (30 mg/kg, p.o.). Gastroprotective effect of AdipoRon (dose 5 and 50 mg/kg p.o.) was compared to omeprazole (20 mg/kg p.o.) or 5% DMSO solution (control). Clinical parameters of gastroprotection were assessed using macroscopic (gastric lesion area) and microscopic (evaluation of the gastric mucosa damage) scoring. To establish the molecular mechanism, we measured: myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities; glutathione (GSH) level; and IL-1β, adenosine monophosphate-activated protein kinase (AMPK), and phosphorylated AMPK expression in gastric tissue. Results: AdipoRon produced a gastroprotective effect in both GU mouse models as evidenced by significantly lower macroscopic and microscopic damage scores. AdipoRon exhibited anti-inflammatory effect by reduction in MPO activity and IL-1β expression in the gastric tissue. Moreover, AdipoRon induced antioxidative action, as demonstrated with higher GSH levels, and increased SOD and GPX activity. Conclusions: Activation of AdipoR1 and AdipoR2 using AdipoRon reduced gastric lesions and enhanced cell response to oxidative stress. Our data suggest that AdipoR1 and AdipoR2 activation may be an attractive therapeutic strategy to inhibit development of gastric ulcers.

Knowledge, Attitudes and Practices of Adults in the United Arab Emirates Regarding Helicobacter pylori induced Gastric Ulcers and Cancers.

Objective:The aim of this study is to assess the current level of knowledge, as well as the attitudes and practices (KAP) of the adult population in Sharjah, UAE with regards to H. pylori induced gastric ulcers and gastric cancers. Methods:A cross sectional study of 500 participants was conducted in public venues in Sharjah, UAE through the distribution of a self-administered questionnaire English and Arabic speaking residents aged 18 years and above of both sexes were invited to participate in this study via convenience sampling. Responses were collected and analyzed using SPSS. Results:General knowledge about H. pylori was poor, only 24.6% had heard of H. pylori. 61% of the participants did not know the link between H. pylori and gastric cancer. Only 3% of the participants associated psychological stress with gastric ulcer development. Females had higher knowledge scores (p = 0.008*). Participants with a medical background typically had higher knowledge scores than their peers in other fields of work (p < 0.0001*). Participants’ attitudes towards H. pylori were suboptimal with only 33% willing to seek medical help If they get symptoms. Majority of participants with an approximate of 84% showed an overall average to excellent practices towards H. pylori. Conclusion:General awareness about H. pylori induced gastric ulcers and cancers is poor. The results of this study can be a starting point to devise new education programs and campaigns that raise awareness of this health issue which could be easily avoided with prevention, early detection, and intervention.

Pharmaceuticals agents for preventing NSAID-induced gastric ulcers: a patent review

ABSTRACT Introduction Nonsteroidal anti-inflammatory drugs (NSAIDs) are a class of drugs widely used due to their pharmacological potential, demonstrating anti-inflammatory, analgesic, or antipyretic activity. However, prolonged use of these medications can lead to the development of gastric ulcers in patients. This review aimed to find patents for drugs with an anti-inflammatory and gastroprotective character to treat NSAID-induced gastric ulcers. Areas covered For the treatment of NSAID-induced gastric ulcers, formulations with different action mechanisms were found, including donors of nitric oxide, heterocyclic compounds, and natural products. Expert Opinion Many of the structures found have already been used in clinic settings and others, and according to the results found, they are promising for the treatment of gastric ulcers.