Gastric Ulcers In Rats Research Articles

Malva parviflora Leaves and Fruits Mucilage as Natural Sources of Anti-Inflammatory, Antitussive and Gastro-Protective Agents: A Comparative Study Using Rat Models and Gas Chromatography.

Malva parviflora L., Little mallow, has been traditionally used as an alternative food source. It acts as a medicinal herb containing a potential source of mucilage thus herein; we aimed to assess the toxicity, anti-inflammatory, antitussive and gastro-protective actions of M. parviflora mucilage extracted from its leaves (MLM) and fruit (MFM). Toxicity studies were investigated by in vitro hemolytic assay whereas acute anti-inflammatory and antitussive activities were assessed by carrageenan-induced paw edema and sulphur dioxide induced cough model in rats, respectively. Gastro-protective effects were studied using ethanol induced acute and chronic gastric ulcer rat models. Their metabolic profiles were determined using gas chromatography. The results revealed that MLM and MFM were non-toxic towards human erythrocytes and their lethal doses were found to be greater than 5 g/kg. Pretreatment with MLM (500 mg/kg) and MFM (500 mg/kg) significantly reduced the carrageenan-induced paw thickness (p < 0.001). Maximum edema inhibition (%) was observed at 4 h in diclofenac sodium (39.31%) followed by MLM (27.35%) and MFM (15.68%). Animals pretreated with MLM (500 mg/kg) significantly lower the cough frequency in SO2 gas induced cough models in contrast to control. Moreover, MLM at doses of 250 and 500 mg/kg reduced the ethanol induced gastric mucosal injuries in acute gastric ulcer models presenting ulcer inhibition of 23.04 and 38.74%, respectively. The chronic gastric ulcer model MFM (500 mg/kg) demonstrated a remarkable gastro-protective effect showing 63.52% ulcer inhibition and results were closely related to standard drug sucralfate. In both models, MLM and MFM decreased gastric juice volume and total acidity in addition to an increased gastric juice pH and gastric mucous content justifying an anti-secretary role of this mucilage that was further confirmed by histopathological examination. Meanwhile, GC analyses of the mucilage revealed their richness with natural as well as acidic monosaccharides. It is concluded that MLM and MFM can be used therapeutically for the management of inflammation, cough and gastric ulcer.

Evaluation of Gastroprotective Effect from Phaleria macrocarpa Fruits Extract on Gastric Ulcer in Male Wistar Rats

Abstract&#x0D; &#x0D; BACKGROUND: The long-term use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) triggers gastric mucosal damage and causes ulcers. Meanwhile, studies showed that God's crown fruit (Phaleria macrocarpa) contains secondary metabolites of flavonoids and tannins that can protect the gastric mucosa.&#x0D; AIM: This study aims to determine the gastroprotective effect of P. macrocarpa ethanolic extracts against gastric ulcers in rats induced with acetosal and ethanol. The extracts were obtained by maceration method using 96% ethanol as solvent.&#x0D; METHODS: The male rats used were divided into 7 groups for each test with ethanol and acetosal induction. Each group consisted of 5 rats, namely normal control, induction, carrier, positive control (sucralfate 360 mg/kg BW and omeprazole 3.6 mg/kg BW), and extract doses 100, 200, and 400 mg/kg body weight. All groups were given treatment for 7 days except normal and induction controls. On day 6, rats were fasted for 36 hours and induced with acetosal/ethanol. In ethanol induction, the animal was sacrificed after 10 hours of immersion while in acetosal, the animal was sacrificed 6 hours later. The stomach section was taken for macroscopic, microscopic parameters and gastric acid secretion examination.&#x0D; RESULTS: The results of phytochemical screening showed that the extract contained flavonoids, tannins, saponins, alkaloids, and glycosides. In acetosal-induced ulcers, the administration of one dose of the extract reduced the number and score of ulcers, repair epithelial cells, increase pH, and total gastric acidity. Furthermore, the percentage of ulcer inhibition at the extract dose of 400 mg/kg BW was 91.91±3.74% in ethanol induction, and 59±13.08% in acetosal.&#x0D; CONCLUSION: The ethanolic extract of P. macrocarpa has a gastroprotective effect on acetosal-induced gastric ulcer rats.&#x0D; &#x0D; Keywords: Phaleria macrocarpa, Mahkota Dewa fruit, gastroprotective, gastric ulcers, extract

The ameliorative effects of cinnamon oil against ethanol-induced gastric ulcer in rats by regulating oxidative stress and promoting angiogenesis.

Cinnamonis one of the herbal resources belonging to the Lauraceae family, is commonly used in traditional medicine and as a flavoring agent. It has antioxidant and anti-inflammatory activities. Therefore, the present study was performed to evaluate the gastroprotective effect of cinnamon on ethanol-induced gastric ulcer in comparison to omeprazole. In Wistar rats, gastric ulcers were induced using one oral dose of 70% ethanol (5ml/kg b. w.) Cinnamon oil at doses of 2.5ml/kg body weight and omeprazole (a reference drug) at a dose of 20mg/kg body weight were orally administrated daily for 7days before ulcer induction. 1 h after ethanol administration blood samples were collected and then the stomachs of sacrificed rats were subjected to biochemical, macroscopic and histological, and immunohistochemical studies. Oral administration ofcinnamon oil significantly attenuated gastric ulcer as revealed by a significant increase in the gastric levels of enzymatic and non-enzymatic antioxidants namely CAT, SOD, GSH-Px, and GSH with a concomitant reduction in MDA level compared with those in the ethanol group. Pre-treatment ofcinnamon oil markedly improved the level of TNF-α and PGE content. Furthermore,cinnamon oilpre-treatment significantly increased the immunoreactivity of VEGF while decreasing the immunoreactivity of COX-II. These results were further supported by histopathological findings which revealed the curing effect ofcinnamon oilon the microscopic changes induced by ethanol toxicity. Cinnamon oil showed a potential gastroprotective effect on ethanol-induced gastric ulcer comparable to the gastroprotective effect of omeprazole, and its effect may be mediated through suppression of oxidative stress and gastric inflammation and promotion of angiogenesis.

Gastroprotective effect of an active ingredients group of Lindera reflexa Hemsl. On Ethanol-Induced gastric ulcers in Rats: Involvement of VEGFR2/ERK and TLR-2/Myd88 signaling pathway

Lindera reflexa Hemsl. (LR) has been used for the treatment of gastrointestinal disorders. The present study was carried out to investigate the gastroprotective effect of an active ingredients group of Lindera reflexa Hemsl. (LRG) on ethanol-induced gastric ulcer in rats and its possible mechanisms. The ulcer area was measured, and samples of gastric tissue were taken for histochemical, pathological, and biochemical analyses. Pretreatment with LRG protected the gastric mucosa as seen by reduction the GUI and gastric juice volume, regulated gastric acid secretion. LRG counteracted the ethanol-induced oxidative stress by increasing the levels of depleted SOD and CAT as well as significantly attenuating the lipid peroxidation by reducing the levels of MDA and MPO. LRG also reduced release of inflammatory mediator TNF-α, increased the content of PGE2 and inhibited MTL secretion. Immunofluorescence and Western blot analyses confirmed that the co-localization of TLR-2 and MyD88 protein in the gastric mucosa of LRG-treated rats was significantly lower than that of rats with gastric ulcers. Furthermore, LRG also modulated the expression of Ki-67 antigens. LRG markedly increased the expression of phosphorylated form of extracellular signal-regulated kinaseVEGFR2, ERK1/2, AKT and p38, thereby protecting the gastric mucosa. These findings indicated that the gastroprotective effect of LRG is attributable to its antioxidant, anti-inflammatory, and antisecretory properties. In addition, LRG can ameliorate ethanol-induced gastric ulcers in rats by regulating the VEGFR2/ERK and TLR-2/MyD88 signaling pathways.

Effect and mechanism of Jingqi Yukui Capsules on gastric ulcer mucosa healing quality: based on network pharmacology and animal experiment

This study aims to identify the active components and the mechanism of Jingqi Yukui Capsules(JQYK) in the treatment of gastric ulcer based on network pharmacology, and verify some key targets and signaling pathways through animal experiment. To be specific, first, the active components and targets of JQYK were retrieved from a Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM) and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the targets of gastric ulcer from GeneCards and Online Mendelian Inheritance in Man(OMIM) with the search term &quot;gastric ulcer&quot;. The common targets of the two were the potential targets of the prescription for the treatment of the di-sease. Then, protein-protein interaction(PPI) network of key targets were constructed based on STRING and Cytoscape 3.7.2, followed by Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment by matescape database and pathway visualization by Omicshare. For the animal experiment, the improved method of Okabe was used to induce gastric ulcer in rats, and the model rats were classified into the model group, JQYK high-dose(JQYK-H), medium-dose(JQYK-M), and low-dose(JQYK-L) groups, Anweiyang Capsules(WYA) group, and Rabeprazole Sodium Enteric Capsules(RBPZ) group. Normal rats were included in the blank group. Rats in the blank group and model group were given distilled water and those in the administration groups received corresponding drugs. Then gastric ulcer healing in rats was observed. The changes of the gastric histomorphology in rats were evaluated based on hematoxylin-eosin(HE) staining, and the content of inducible nitric oxide synthase(iNOS) in rat gastric tissue was detected with Coomassie brilliant blue method. The mRNA and protein levels of some proteins in rat gastric tissue were determined by real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot(WB) to further validate some key targets and signaling pathways. A total of 206 active components and 535 targets of JQYK, 1 305 targets of gastric ulcer, and 166 common targets of the disease and the drug were yielded. According to PPI analysis and KEGG pathway enrichment analysis, multiple key targets, such as interleukin-6(IL-6), tumor necrosis factor(TNF), mitogen-activated protein kinase 1(MAPK1), MAPK3, and MAPK14, as well as nuclear factor kappa-B(NF-κB) signaling pathway, IL-17 signaling pathway, and leukocyte transendothelial migration in the top 20 key signaling pathways were closely related to inflammation. The key protein p38 MAPK and NF-κB signaling pathway were selected for further verification by animal experiment. The gastric ulcer in the JQYK-H group recovered nearly to the level in the blank group, with significant decrease in the content of iNOS in rat gastric tissue and significant reduction in the mRNA and phosphorylation levels of p38 MAPK and the mRNA and protein levels of NF-κB p65 in rat gastric tissue. The results indicated that JQYK can inhibit the phosphorylation of the key protein p38 MAPK and the expression of NF-κB p65 in the NF-κB signaling pathway, thereby exerting the anti-inflammatory effect and effectively improving the quality of gastric ulcer healing in rats. Thus, the animal experiment result verifies some predictions of network pharmacology.

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.

Emblica officinalis Fruit Pulp Extract Protects against Naproxen-Induced Gastric Ulcer in Rats: Anti-inflammatory and Antioxidant Machinery

Background: The use of non-steroidal anti-inflammatory drugs (NSAIDs) is one of the leading causes of peptic ulcers. There is a rising interest and demand for nontoxic, antiulcer remedies derived from medicinal plants to treat NSAID-induced gastric ulcers (GU). Aim: This study is a comparative assessment of the possible gastro-protective role of Emblica officinalis fruit pulp extract (EOFPE) and Omeprazole (Omepra) against Naproxin (Naprox)-induced GU. Methodology: Five groups of rats (8 rats each) represent control, Naprox, Omepra (20 mg/kg), EOFPE (700 mg/kg), and EOFPE + Omepra. Omepra and EOFPE were ingested orally for 17 days. Naprox was ingested orally on day 15 for three consecutive days. Results: Pretreatment with EOFPE and/or Omepra caused significant increases in gastric pH and gastric mucin content. Besides, significant decline in the total gastric acidity and gastric mucosal lesion relative to the Naprox group. Pretreatment with EOFPE and/or Omepra markedly improved the examined gastric pathologic features in Naprox-pretreated groups. Besides, EOFPE and/or Omepra overcome the gastric inflammation and oxidative stress markers induced by Naprox ingestion. Pretreatment with both EOFPE + Omepra leads to the best antiulcer impact and lesion inhibition percent relative to the Naprox groups pretreated with either EOFPE or Omepra alone. Conclusion: EOFPE protected against Naprox-induced GU across anti-inflammatory and antioxidant mechanisms. Keywords: Antioxidant, Anti-inflammatory, Emblica officinalis, Gastric ulcer.

Ginkgolide protects against ethanol-induced gastric ulcer in rats through NLRP3 related pathway

Ginkgolide protects against ethanol-induced gastric ulcer in rats through NLRP3 related pathway

Antiulcer activity of proanthocyanidins is mediated via suppression of oxidative, inflammatory, and apoptotic machineries.

Gastric ulcer (GU) is a lesion in the gastric mucosa associated with excessive oxidative damage, inflammatory response, apoptotic events, and irritation which may develop into cancer. However, medications commonly used in GU treatment cannot normalize gastric mucosa, while causing several adverse effects. Proanthocyanidins (PAs) are dietary flavonoids with numerous biological and pharmacological activities. In the current investigation, we studied the potential anti-ulcerative activity of PAs against acidified ethanol (HCl/ethanol)-caused gastric ulceration. Fifty male albino Wistar rats were allocated into five equal groups: control, HCl/ethanol (3mL/kg), lansoprazole (LPZ, 30mg/kg)+HCl/ethanol, and PAs (100 and 250mg/kg)+HCl/ethanol. LPZ and PAs were applied one week before gastric ulcer induction. PAs pretreatment notably reduced gastric mucosal macroscopic and microscopic pathological changes in a dose-dependent manner. Additionally, PAs activated the innate antioxidant molecules including glutathione and its derived antioxidants (glutathione peroxidase and glutathione reductase), along with superoxide dismutase and catalase, while attenuating pro-oxidant formation, including malondialdehyde and nitric oxide. Interestingly, PAs supplementation at a higher dose suppressed gastric inflammatory and apoptotic responses, as demonstrated by the reduced levels of interleukin-1β, interleukin-6, tumor necrosis factor alpha, high-mobility group box 1, cyclooxygenase 2, prostaglandin E2, nuclear factor kappa-B, Bcl-2-associated X protein, and caspase-3, while B cell lymphoma 2 was elevated. Hence, PAs could exhibit antiulcer activity by protecting gastric tissue from the development of oxidative damage, inflammatory responses, and apoptosis events associated with ulceration. PRACTICAL IMPLICATIONS: Gastric ulcer is a lesion in the gastric mucosal layer associated with excessive inflammatory response, apoptotic events, oxidative damage, and irritation, and may develop into cancer with about 5%-10% morbidity rate. However, medications commonly used in GU treatment cannot normalize gastric mucosa, while causing several adverse effects. Therefore, new therapeutic approaches are needed to treat or prevent gastric ulceration. Proanthocyanidins (PAs, condensed tannins) are dietary flavonoids found in abundance in different plant species, including their fruits, bark, and seeds. Due to their potent antioxidative activity, PAs have been applied to prevent or treat oxidative stress-related diseases, including cancer, as well as metabolic, neurodegenerative, cardiovascular, and inflammatory disorders. Here, we examine the potential therapeutic role of proanthocyanidins (PAs) against acidified ethanol-induced gastric ulcer in rats through evaluating oxidative challenge, inflammatory response, apoptotic events, and histopathological changes in the gastric tissue.

Protective effect of chrysin on indomethacin induced gastric ulcer in rats: role of multi-pathway regulation

ABSTRACT We investigated the potential gastroprotective effects of chrysin on indomethacin induced gastric ulcers in rats. We used six groups of animals: control; indomethacin (Indo); reference (Ulcuran®); indomethacin + 25 mg/kg chrysin (Indo + CHR25); indomethacin + 50 mg/kg chrysin (Indo + CHR50); indomethacin + 100 mg/kg chrysin (Indo + CHR100). All doses of chrysin were given orally to rats before indomethacin. Gastric lesions were examined macroscopically and microscopically. The effects of treatment with chrysin were assessed versus a single dose of 30 mg/kg Ulcuran® (generic ranitidine) as reference standard. We also investigated gastric mucosal superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), malonaldehyde (MDA) and arginase activities, and COX-2, PGE2, iNOS, TNF-α, IL-1β, NFκB, MPO, Bax, caspase-3 and 8-OHdG levels. We assessed caspase-3 and Bax levels using immunohistochemistry. Compared to the control and reference groups, SOD, CAT, GPx and arginase activities and GSH levels decreased, and MDA levels increased in the indomethacin induced gastric ulcer group. iNOS, TNF-α, IL-1β, NFκB, MAPK-14, MPO, Bax and 8-OHdG levels were increased in the indomethacin treated gastric group, while COX-2 activity and PGE2 levels were decreased. The three doses of chrysin co-administered with indomethacin increased COX-2 activity and PGE2 levels in rats with ulcers. Chrysin exhibited gastroprotective effects on indomethacin induced gastric ulcer due to its antioxidant, anti-inflammatory and anti-apoptotic activities.

Protective Effect of Nigella sativa Seeds Extract against Ethanol-Induced Gastric Ulcer in Rats: Possible Soluble Epoxide Hydrolase Inhibition

Nigella sativa seeds methanolic extract was prepared by a simple maceration process. The extract was subjected to preliminary phytochemical screening and high-performance thin-layer chromatography for linoleic and linolenic acid and tested for in vitro soluble epoxide hydrolase inhibition activity. Then the extract (100, 150 and 200 mg/kg) was evaluated against ethanol-induced stomach ulcer in rats using 1-(1-propanoylpiperidin-4-yl)-3-(4-trifluoromethoxy)phenyl) urea (1 mg/kg) and omeprazole (20 mg/ kg) as reference standards. The plant extract contains flavonoids, alkaloids, proteins, free amino acids, tannins, flavonoids and linoleic acid. The in vitro soluble epoxide hydrolase inhibition test results reveal that Nigella sativa seeds methanolic extract inhibit human soluble epoxide hydrolase enzyme (half maximal inhibitory concentration=2.619 μg/ml). The Nigella sativa seeds methanolic extract reversed macroscopic and microscopic alteration and attenuated the levels of myeloperoxidase, tumour necrosis factor-alpha, interleukin-6, 5-hydroxyeicosatetraenoic acid in ulcer rats. These results were comparable with standard control. In conclusion, Nigella sativa seeds methanolic extract has a protective action against ethanolinduced ulcers in rats.

Healing effect of hydroalcoholic extract of Humulus lupulus L. (Hops) aerial parts on indomethacin-induced gastric ulcer in rats

Healing effect of hydroalcoholic extract of Humulus lupulus L. (Hops) aerial parts on indomethacin-induced gastric ulcer in rats

Gastroprotective and Antioxidative Effects of the Traditional Thai Polyherbal Formula Phy-Blica-D against Ethanol-Induced Gastric Ulcers in Rats.

Phy-Blica-D is a traditional Thai polyherbal formula that has reduced oxidative stress in non-communicable diseases. However, evidence supporting the gastroprotective effects of Phy-Blica-D has not been previously reported. Therefore, this study aimed to evaluate the gastroprotective effects of Phy-Blica-D against gastric ulcers in rats and investigate the potential underlying mechanism. To estimate the possible mechanisms of action, we examined the levels of oxidative stress markers, such as reactive oxygen species (ROS) and malondialdehyde (MDA), as well as antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH). According to our results, rats treated with only 80% ethanol (vehicle group) exhibited significant increases in their ulcer area and ulcer index (UI). Moreover, the levels of ROS and MDA markedly increased in the vehicle group compared with the normal control group. Daily oral administration of Phy-Blica-D (500 and 1000 mg/kg) for 7 days not only significantly decreased the ulcer area and UI, but also remarkably decreased the ROS and MDA levels in gastric tissue. Gastric ulcers induced by ethanol had significantly decreased antioxidant enzyme activities (CAT and SOD) and non-enzymatic antioxidant (GSH), whereas pretreatment with Phy-Blica-D significantly improved the activities of CAT, SOD, and GSH. Moreover, after exposure to ethanol, the rats exhibited a significantly increased level of inducible nitric oxide synthase (iNOS), which was reduced after treatment with Phy-Blica-D. These findings suggest that Phy-Blica-D potentially exerts its gastroprotective effects by suppressing oxidative stress and stimulating antioxidant enzymes, which is one of the causes of destruction of cell membranes, and it is involved in the pathogenesis of acute gastric ulcers induced by ethanol.

Redox-Based Theranostics of Gastric Ulcers Using Nitroxyl Radicals.

Significance: Redox-based theranostics involves redox monitoring and therapeutics that normalize redox imbalance. It may be a promising approach to markedly improve a patient's quality of life through streamlined treatment. Nitroxyl radicals are useful for both redox monitoring and treating gastric ulcers in rodents. Recent Advances: Redox monitoring using in vivo electron paramagnetic resonance (EPR) spectroscopy in a gastric ulcer rat model showed the production of reactive oxygen species in the whole stomach. A combination of Overhauser-enhanced magnetic resonance imaging (MRI) and nitroxyl radicals provided high-resolution images of redox imbalance in the stomach of rats with a gastric ulcer. Treatment with nitroxyl radicals was effective to treat ulcers that were formed using model experiments of Helicobacter pylori and mental stress as well as nonsteroidal anti-inflammatory drugs. Critical Issues: For redox monitoring using Overhauser-enhanced MRI, the EPR irradiation power that is delivered to subjects must be within the range of the specific absorption rate regulation to protect against microwave damage regardless of a decrease in image contrast. The effect of long-term treatment with a nitroxyl radical in patients with a gastric ulcer remains unclear. Future Directions: Further research on redox-based theranostics in redox-related diseases, including gastric ulcers, would be accelerated by improving the redox imager and by developing functional nitroxyl radicals that localize in the target organ, tissue, or cell and that have specific reactivity for the redox-related biomolecule.

Preventive Activity of Muntingia calabura Fruits Extract in Aspirin-induced Gastric Ulcer Rat

Gastric ulcer can be affected people at any age. One cause of this disease is NSAID usage. The aim of this study is to determine Muntingia calabura L. fruit activity for prevent ulcer using aspirin-induced gastric ulcer in rat model. Thirty male Wistar rats were divided become six groups: normal (CMC 0.5%), negative control (CMC 0.5%), positive control (omeprazole 20 mg/kg), treatment group (ethanol M . calabura L. fruit extract): I (100 mg/kg), II (200 mg/kg), and III (300 mg/kg) and given orally once a day for 9 days. On the 10th day, aspirin at a dose of 500 mg/kg was given to all groups except the normal group. Four hours after induction, all animals were sacrificed. Preventive effect against stomach ulcer were determined by calculating the index of ulcer and histopathological examination. Index ulcer of M. calabura fruit extract at all dose were different than negative group, although not significant (p&lt;0.05). Histopathological examination of M. calabura extract at a dose of 300 mg/kg showed few inflammatory cells and congestion compared with the other treatment group. Therefore, ethanol M . calabura L. fruit extract at a dose 300mg/kg gave best activity in preventive of gastric ulcer. Keywords: aspirin, gastric ulcer, Muntingia calabura fruit

Antimicrobial Activity of Brassica rapa L. Flowers Extract on Gastrointestinal Tract Infections and Antiulcer Potential Against Indomethacin-Induced Gastric Ulcer in Rats Supported by Metabolomics Profiling.

IntroductionThe gastrointestinal tract (GIT) is vulnerable to various diseases. In this study, we explored the therapeutic effects of Brassica rapa flower extract (BRFE) on GIT diseases.MethodsLiquid chromatography–electrospray ionization–tandem mass spectrometry (LC-ESI-MS/MS) was used for phytochemical identification of the compounds in BRFE. The antibacterial activity of BRFE was investigated, and its impact on the bacterial outer and inner membrane permeability and membrane depolarization (using flow cytometry) was studied. In addition, the immunomodulatory activity of BRFE was investigated in vitro on lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Furthermore, the anti-inflammatory activity of BRFE was investigated by histopathological examination and qRT-PCR on indomethacin-induced gastric ulcers in rats.Results and DiscussionLC-ESI-MS/MS phytochemically identified 57 compounds in BRFE for the first time. BRFE displayed antibacterial activity against bacteria that cause GIT infections, with increasing outer and inner membrane permeability. However, membrane depolarization was unaffected. BRFE also exhibited immunomodulatory activity in LPS-stimulated PBMCs by attenuating the upregulation of cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa B (NF-κB) gene expression compared with untreated LPS-stimulated PBMCs. In addition, BRFE exhibited anti-inflammatory activity required for maintaining gastric mucosa homeostasis by decreasing neutrophil infiltration with subsequent myeloperoxidase production, in addition to an increase in glutathione peroxidase (GPx) activity. Histopathological findings presented the gastroprotective effects of BRFE, as a relatively normal stomach mucosa was found in treated rats. In addition, BRFE modulated the expression of genes encoding IL-10, NF-κB, GPx, and myeloperoxidase (MPO).ConclusionBRFE can be a promising source of therapeutic agents for treatment of GIT diseases.

Commiphora myrrh Supplementation Protects and Cures Ethanol-Induced Oxidative Alterations of Gastric Ulceration in Rats.

Gastric ulceration is a multifactorial disease defined as a defect in the gastric wall that extends through the muscularis mucosae into the deeper layers of the wall. The most common cause of gastric ulceration is alcohol consumption. In the current study, rats were gavaged by ethanol to investigate the protective (before ethanol) and curative (after ethanol) ability of Commiphora myrrh (myrrh) oil and extract against gastric ulcer oxidative alterations induced by ethanol. Myrrh significantly improved ulcer index, histomorphology, and periodic acid Schiff (PAS) impaired by ethanol. In addition, myrrh improved the antioxidant potential of gastric mucosa through enhancement of nuclear factor related to erythroid 2 (Nrf2), total glutathione (GSH), reduced GSH, and oxidized glutathione (GSSG), along with significant reduction in malondialdehyde (MDA) levels. Amelioration of gastric oxidative stress by myrrh enables gastric mucosa to counteract the ethanol’s inflammatory and apoptotic processes leading to improved gastric proliferation and healing. Interestingly, myrrh extract showed better protective and curative effects than myrrh oil against gastric ulceration.

Therapeutic Potency of Gallium verum Extract on Ethanol-Induced Gastric Ulcer in Rats

Gallium verum, lady's bedstraw is an herbaceous annual plant belonging to the genus Rubiaceae; it possessed antioxidant, cytotoxic for cancer cells, antimicrobial, protective and endocrine effects. This work aimed to investigate the curative effects of G. verum extract on gastric ulcers following absolute ethanol administration in the healthy rat. Eighteen rats were randomly divided into three main groups; rats were fastened for 24 hours before ethanol administration. All groups except control administered ethanol (5 ml/kg body weight; orally). The rats were administrated distilled water (Ulcer group) or G. verum extract (100mg/kg) one hour later. G. verum extract caused a significant decrease in ulcer index, gastric juice volume, malondialdehyde, and nitric oxide, while gastric juice pH, glutathione, glutathione-S-transferase, and catalase increased significantly. The histological lesion score showed a significant enhancement in group G. verum compared to the ulcer group that scored the highest pathological destruction score. Immunohistochemical markers of NF-κB p65 and TNF-α showed a significant decrease in G. verum group. G. verum extract is a promising treatment modality against gastric injury through its powerful antioxidant, acid neutralizing, healing promotion, and ant-inflammation effects.

Olmesartan niosomes ameliorates the Indomethacin-induced gastric ulcer in rats: Insights on MAPK and Nrf2/HO-1 signaling pathway.

Gastric ulcer is a continuous worldwide threat that inquires protective agents. Olmesartan (OLM) has potent anti-oxidant and anti-inflammatory characters, yet having limited bioavailability. We targeted the gastro-protective potential and probable mechanism of OLM and its niosomal form against indomethacin (IND) induced-gastric ulcer in rats. we prepared OLM niosomes (OLM-NIO) with different surfactant: cholesterol molar ratios. We evaluated particle size, zeta-potential, polydispersity, and entrapment efficiency. In-vitro release study, Fourier transform infrared spectroscopy, differential scanning calorimetry, and transmission electron microscopy were performed for selected niosomes. In-vivo, we used oral Omeprazole (30mg/kg), OLM or OLM-NIO (10mg/kg) for 3days before IND (25mg/kg) ingestion. We assessed gastric lesions, oxidative and inflammatory markers. OLM-NIO prepared with span 60:cholesterol ratio (1:1) showed high entrapment efficiency 93 ± 2%, small particle size 159.3 ± 6.8nm, low polydispersity 0.229 ± 0.009, and high zeta-potential -35.3 ± 1.2mV, with sustained release mechanism by release data. In-vivo macroscopical and histological results showed gastro-protective effects of OLM pretreatment, which improved oxidative stress parameters and enhanced the gastric mucosal cyclooxygenase-1 (COX-1) and prostaglandin E2 (PGE2) contents. OLM pretreatment suppressed interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) contents and translocation of p38 mitogen-activated protein kinase (p38-MAPK). Besides, OLM substantially promoted the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) protective pathway. OLM-NIO furtherly improved all previous outcomes. We explored OLM anti-ulcerative effects, implicating oxidative stress and inflammation improvement, mediated by the Nrf2/HO-1 signaling pathway and p38-MAPK translocation. Meanwhile, the more bioavailable OLM-NIO achieved better gastro-protective effects compared to conventional OLM form.

Comparative Evaluation of Gastroprotective Potential of Dypsis lutescens (H. Wendl.) and Caryota Urens(L.) on Experimentally Induced Gastric Ulcer in Rats

The present study was carried out to find out the gastroprotective effects of the leaves extracts of Dypsis lutescens (H.Wendl.) and Caryota Urens (L.) in aspirin-induced gastric ulcer in rats. The ethanolic and aqueous extracts were prepared from the leaves of Dypsis lutescens and Caryota Urens and were used for this study. All procured animals were divided into seven groups. Each group contain n = 6, all groups except the normal control treated with aspirin 150 mg/kg oral. Group, I served as the normal control group which received normal saline, group II served as negative control and group III as standard group receiving 20 mg/kg omeprazole and 4th to 7th groups treated with leaves extracts of Dypsis lutescens and Caryota urens respectively. Treatment was given to group II to group VII rats in every 24 h for seven days. After 24 h fasting, on the 8th-day stomach contents were aspirated under anaesthetic condition to check free and total acidity. Stomachs were opened in all sacrificed animals along the greater curvature to estimate ulcer index, percentage protection and histopathology studies.&#x0D; The results of the present study revealed that the severity of aspirin-induced ulceration was significantly (P &lt; 0.05) decreased in Dypsis lutescens extracts treated groups in comparison with the control and Caryota urens treated groups. It was observed that the free and total acidity significantly decreased in the aqueous extract of Dypsis lutescens treated group when compared with the negative control and Caryota urens treated groups.