Ethanol-induced Gastric Ulcer Model Research Articles

Antioxidant and gastroprotective effects of the ethyl acetate extract from Stemodia maritima L. in ethanol-induced gastric ulcer model

Stemodia maritima L., is a shrub of the Plantaginaceae family, with some biological activities already described, such as: larvicide, antimicrobial, and anti-inflammatory. Thus, the objective of this work was to evaluate the antioxidant, and gastroprotective activities of the ethyl acetate extract from S. maritima. The phytochemical profile was investigated through the quantification of total phenolic compounds, flavonoids, and CCD analysis. The toxicity of the extract was performed through cell viability using L929 line cell, and acute toxicity by the OECD Guide 423. The antioxidant activity was analyzed by the methods of reduction of the ferric ion (FRAP), total antioxidant activity (TAA), and the gastroprotective activity by the absolute ethanol-induced gastric ulcer model, with analysis of NO, MDA, GSH and MPO levels in the stomach tissues. In the phytochemical profile it was possible to identify the presence of flavonoids, triterpenes, steroids, mono, and sesquiterpenes. The extract was not cytotoxic against L929 lineage, maintaining cell viability above 70% at the doses tested, and in acute toxicity it did not show physiological changes indicative of toxicity compared to the control group. The extract presented antioxidant activity of 157.3 ± 9.7 mg equivalent of Trolox/g of extract in the FRAP method, and 50.0 ± 1.1 % by TAA. The ethyl acetate extract of S. maritima, at the doses tested, reduced the ulcerative lesion index compared to the injured control group, increased the levels of NO and GSH, and was able to decrease the concentrations of MDA and MPO, enhancing their gastroprotective activity.

Effectiveness of the fruit of Rosa odorata sweet var. gigantea (Coll. et Hemsl.) Rehd. et Wils in the protection and the healing of ethanol-induced rat gastric mucosa ulcer based on Nrf2/NF-κB pathway regulation

Ethnopharmacological relevanceRosa odorata Sweet var. gigantea (Coll. et Hemsl.) Rehd. et Wils (Rosaceae), is also known as “GU-GONG-GUO”, the root of which has been recognized as common ethnodrug from the Yi nationality for treating inflammatory bowel disease. The aim of the present study was to investigate the preventive and curative effects of extract from the fruits of Rosa odorata Sweet var. gigantea (Coll.et Hemsl.) Rehd. et Wils (FOE) in vitro and in vivo as well as elucidate the potential mechanisms of the action involved. Materials and methodsMale Wistar rats were applied to ethanol-induced gastric ulcer model. They were divided into six groups: control, model (GU), positive (Magnesium aluminate chewable tablets, 125 mg/kg), FOE low (125 mg/kg), middle (250 mg/kg) and high (500 mg/kg) doses groups. Histopathology observation of gastric tissues was detected by hematoxylin and eosin (H&E) staining. The expression of Nrf2, HO-1, Keap1, NF-κB p65 and IKKα/β in gastric tissues were evaluated by immunohistochemistry (IHC). The levels of cytokines in serum and tissues were measured by Enzyme-linked immunosorbent assay (ELISA). The expression of Nrf2, HO-1, Keap1, NF-κB p65, IKKα/β, PCNA and COX2 proteins were ulteriorly assessed by Western blotting to elucidate the molecular mechanism of FOE's protective effect on gastric ulcer. ResultsMTT detection showed that LPS reduced RAW264.7 cell survival, and FOE blocked the inhibition of RAW264.7 cell growth induced by LPS. When RAW264.7 cells were treated with both FOE (100 μg mL−1) and LPS (5 μg mL−1) for 24 h, compared with the model group, the level of NO, TNF-α, IL-6, IL-1β and MDA significantly decreased, and the activity of SOD was significantly reduced. Obvious pathological injuries in the GU model group were observed, which was improved after treatments with FOE. The contents of pro-inflammatory factors in serum and tissues were decreased by 25% whereas prostaglandin E2 (PGE2) and epidermal growth factor (EGF) were increased by 30% in a dose-dependent manner after FOE (500 mg/kg) treatments. In addition to the promotion effects of superoxide dismutase (SOD), FOE (500 mg/kg) also attenuated the levels of nitric oxide (NO) and malondialdehyde (MDA) by 20%. Likewise, the expression of NF-κB p65, IKKα/β and Keap1 were suppressed after treatments with FOE whereas Nrf2 and HO-1 showed the opposite trend, which mechanisms were found to be associated with Nrf2/NF-κB signaling pathways. ConclusionThe study demonstrated that FOE is able to protect against GU via inhibiting NF-κB signaling pathway and activating Nrf2 signaling pathway, which might provide a stronger theoretical basis for the treatment of GU.

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 effect of snail\xa0secretion filtrate against ethanol-induced gastric ulcer in mice

Gastric ulcer or peptic ulcer is a common disease worldwide. Basically, it develops when there is an imbalance between the protective and aggressive factors, especially at the luminal surface of epithelial cells. Thus, there is a constant interest in research new drugs for treatment of gastric ulcer. The snail secretion is a dense mucous, that covers the external surface of the snails, with important functions for the survival of snails. The biological proprieties of snail Helix Aspersa Muller mucus it has been known for centuries to treat human disorders in particular for skin disease. Recently the use of snail mucus has seen a worldwide increase, as a component in cosmetic product and it has been used in particular for the management of wound and skin disorders. In this study we use a murine model of ethanol intragastric administration which has been widely used to test the drugs efficacies and to explore the underlying mechanism for gastric ulcer development. The intragastric ethanol administration causes several mucosal damages and an induction of a severe inflammatory response. Our results show a significant protective effect of snail secretion filtrate in reducing macroscopic and histological lesions, as well the protective effect on mucus content, oxidative stress and inflammatory response. In conclusion this study demonstrate the protective effect of intragastrical snail secretion filtrate, in a model of ethanol-induced gastric ulcer in mice, suggesting its possible useful use in the treatment or prevention of gastric ulcer.

Nerolidol-beta-cyclodextrin inclusion complex enhances anti-inflammatory activity in arthritis model and improves gastric protection

Rheumatoid arthritis is an autoimmune inflammatory disease with progressive degradation of cartilage and joints. Additionally, gastric ulcer affects many patients who make prolonged use of non-steroidal anti-inflammatory drugs widely used in the symptomatic treatment of rheumatoid arthritis. Nerolidol, a natural sesquiterpene, has several biological activities including anti-inflammatory and antiulcerogenic action. This study aims to develop and characterize a nerolidol ß-cyclodextrin inclusion complex and to evaluate its activity in an experimental arthritis model. Inclusion complex was prepared by the lyophilization method and characterized by NMR, term analysis, XRD and SEM. Neutrophil migration assays and histopathological analysis were performed on zymosan-induced arthritis model using Swiss mice. And the gastroprotective effect was evaluated in two models of gastric ulcers: induced by ethanol and indomethacin. Inclusion complex showed no cytotoxicity and free nerolidol at a dose of 100 mg/kg (p.o.) in the arthritis model reduced neutrophil migration in 56% in relation to vehicle, and this inhibition was more expressive in the inclusion complex (67%) at the same dose. Histopathological analysis of the joint tissue confirmed the reduction of inflammatory signs. In the ethanol-induced gastric ulcer model, free nerolidol reduced the relative ulcer area more expressively (4.64%) than the inclusion complex (21.3%). However, in the indomethacin induction model, the inclusion complex showed better results in gastric protection compared to free nerolidol. The action of nerolidol complexed in beta-cyclodextrin in reducing arthritis inflammation combined with its gastroprotective action make it a potential new drug.

Royal jelly attenuates gastric mucosal injury in a rat ethanol-induced gastric injury model.

The aim of the study was to investigate traditionally used Royal Jelly (RJ) for treating an ethanol-induced gastric ulcer model in rats. A total of 32 Wistar albino male rats were divided into 4 groups of 8: group I = Control, group II = Ethanol, group III = RJ + Ethanol, and group IV = Lansoprazole + Ethanol. In groups II, III, and IV, animals were administered 1ml of absolute ethanol orally after a 24-h fast to induce ulcer formation. The histopathological changes in the gastric mucosa were determined using hematoxylin-eosin (H&E) staining. Immunohistochemically, inducible nitric oxide (iNOS) and nuclear factor kappa beta (Nf-κβ) markings were evaluated in gastric tissue. Cell death in the gastric mucosa was determined by the TUNEL method. Oxidative status markers, superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), and myeloperoxidase (MPO) levels were determined spectrophotometrically. Expression of the interleukin - 1 beta (IL-1β) and tumor necrosis factor-α (TNF-α) genes in gastric tissues was determined by real-time PCR; and TNF-α, IL-10, and IL-1β levels were determined. RJ was found to inhibit iNOS and Nf-κβ activity in the gastric mucosa and prevent epithelial cell apoptosis. In particular, pro-inflammatory cytokines TNF-α and IL-1β levels were significantly decreased in the RJ + Ethanol group compared to the Ethanol group. In addition, a decrease in the MPO level indicated that RJ prevented tissue damage, especially by preventing inflammatory cell infiltration. The study demonstrated a possible gastroprotective effect of RJ in a rat ethanol-induced gastric ulcer model.

Natural deep eutectic solvent (NADES)-based blueberry extracts protect against ethanol-induced gastric ulcer in rats

Blueberry is a polyphenol-rich fruit bearing great bioactive potential. Natural deep eutectic solvents (NADES) emerged as putatively biocompatible solvents that could substitute for toxic organic solvents in the extraction of fruit phenolic compounds for developing nutraceuticals or functional foods. Therefore, the aim of this study was to investigate the gastroprotective effects and the biocompatibility of a blueberry crude extract (CE) obtained using NADES and of the extract fractions (anthocyanin-rich fraction – ARF; non-anthocyanin phenolic fraction - NAPF) in a model of ethanol-induced gastric ulcer in rats. CE was the NADES-containing, ready-to-use extract that was obtained using choline chloride:glycerol:citric acid NADES (0.5:2:0.5 M ratio). ARF and NAPF were the NADES-free fractions obtained by solid phase purification of CE and were investigated to identify the bioactive fraction responsible for the effects of CE. Animals were treated for 14 days with water, NADES vehicle, CE, ARF, NAPF or lansoprazole (intragastric) and then received ethanol to induce gastric ulcer. CE decreased ulcer index and preserved the integrity of gastric mucosa. The pretreatment with CE or ARF reduced glutathione depletion and the inflammatory response. All treatments, including NADES vehicle reduced protein oxidation and nitric oxide overproduction in ethanol-treated rats. Additionally, ARF increased short-chain fatty acids in feces. These findings suggest that NADES can be used to obtain biocompatible extracts of blueberry that exhibit gastroprotective effects with no need of solvent removal. The gastroprotective effects were mainly associated to ARF but NAPF and even NADES vehicle also contributed to some protective effects.

UPLC-qTOF-MS Phytochemical Profile and Antiulcer Potential of Cyperus conglomeratus Rottb. Alcoholic Extract.

Cyperus has been commonly used as a multi-use medicinal plant in folk medicine worldwide. The objectives of our study were to determine the different metabolites in the Cyperus conglomeratus Rottb. methanol extract, and to assess its in vivo gastroprotective effect in ethanol-induced gastric ulcer model in rats. Serum levels of galactin-3 and TNF-α were employed as biochemical markers. To pinpoint for active agents, comprehensive metabolites profiling of extract via UPLC-qTOF-MS/MS was employed. A total of 77 chromatographic peaks were detected, of which 70 were annotated. The detected metabolites were categorized into phenolic acids and their derivatives, flavonoids, stilbenes, aurones, quinones, terpenes, and steroids. Rats were divided into six groups; healthy control, ulcer control, standard drug group, and 25, 50, 100 mg/kg of C. conglomeratus treated rats. Pre-treatment with C. conglomeratus alcohol extract significantly reduced galactin-3, and TNF-α in ethanol-induced ulcer model at 25, 50, and 100 mg/kg. Further histopathological and histochemical studies revealed moderate erosion of superficial epithelium, few infiltrated inflammatory cells, and depletion of gastric tissue glycoprotein in the ulcer group. Treatment with the extract protected the gastric epithelial cells in a dose-dependent manner. It could be concluded that C. conglomeratus extract provides significant gastroprotective activity in ethanol-induced gastric ulcer and ought to be included in nutraceuticals in the future for ulcer treatment.

Gastroprotective Effect of Chinese Cabbage (Brassica oleracea L. var. pekinensis) Juice in Sprague Dawley Rats

Background: Chinese cabbage or Brassica oleracea L. var. pekinensis is an edible leafy green vegetable in the family of Brassicaceae. Ethnopharmacological studies have shown that the juice of cabbage leaves is commonly used in the treatment of gastrointestinal disorders, irritable bowel syndrome, minor cuts and wounds and mastitis. Objective: This study was aimed to examine the gastroprotective effect of Chinese cabbage (Family: Brassicaceae) juice in rats by using ethanol-induced gastric ulcer model. Methods: Thirty albino male Sprague Dawley rats (150 ± 20 g) were divided into 6 groups with five rats (n = 5) in each group. The normal control group was treated with distilled water while the positive control group was intragastrically administered with omeprazole (20 mg/kg). Cabbage juice at 500 mg/kg was given orally to three experimental groups for 1-day, 7-day and 14-day, respectively. Ethanol (70 % v/v) was orally treated to all rats one hour after the last dose treatment except the normal control group. Results: Results obtained showed that repeated consumption of cabbage juice for 7 days and 14 days exhibited an increase in accumulation mucus and in the levels of superoxide dismutase (SOD), glutathione- s-transferase (GST) and glutathione peroxidase (GSH-Px) as well as a reduction in gastric lesion area induced by ethanol compared with the ulceration control group. Conclusion: In conclusion, the gastroprotective effect of Chinese cabbage juice could be associated with its ability to increase endogenous antioxidant activities of SOD, GST and GSH-Px and mucus secretion in rat stomach.

Chemical profile and gastroprotective effect of Jatropha elliptica (Pohl) Oken roots

Jatropha elliptica (Pohl) Oken (Euphorbiaceae) roots are used in folk medicine to treat gastric ulcers. The purpose of this work was to evaluate the gastroprotective activity of ethanol extract (JER) and hexane fraction (ERH) of J. elliptica roots in mice, as well as to analyze the acute toxicity of the extract and identify the potential active compounds. No signs of toxicity were observed in JER. In both acidified ethanol and indometacin-induced gastric ulcer models, all doses tested of JER and ERH significantly reduced gastric lesions. Dereplication of JER was performed by HPLC-DAD-ESI-MS/MS and resulted in the annotation of compounds fraxetin, propacin, jatrophone and jatropholones A and B. GC–MS analysis of ERH revealed the diterpenes jatrophone, jatropholone A and jatropholone B as the major components. The chemical study of this fraction has led to the isolation of these compounds, in addition to the sequiterpene cyperenoic acid and the diterpene 2β-hydroxyjatrophone, both reported for the first time in J. elliptica. The isolated compounds were tested against L929 cells and only cyperenoic acid and the mixture of jatropholones A and B did not show toxicity, being then selected as good candidates for bioassays using acidified ethanol-induced gastric ulcer model. Cyperenoic acid significantly decreased gastric lesions and preserved gastric mucus layer. The mixture of jatropholones A and B caused a smaller reduction of gastric lesions, without preservation of the gastric mucus layer. The study showed that J. elliptica roots present gastroprotective activity in mice, without causing acute toxic effects. The activity is related, at least in part, to the occurrence of terpenes, mainly the sesquiterpene cyperenoic acid.

Baccharis trimera (carqueja) promotes gastroprotection on ethanol-induced acute gastric ulcer

One of the factors that can promote gastric ulcer is the acute and/or chronic consumption of ethanol. One of the most used therapeutic measures is the use of proton pump inhibitor, like omeprazole. However, these drugs have several side effects, making it necessary to search for new alternatives. To investigate the gastroprotective effect of Baccharis trimera (carqueja) we used an ethanol-induced acute gastric ulcer model. For this, gastric ulcer was induced in rats using absolute ethanol for 2 consecutive days. After analysis of the stomach, an increase in oxidative stress was observed, as well as the reduction of the antioxidant defense. In addition, we observed in histology that there was an increase in inflammatory cells, necrosis, hemorrhage and hyperemia. Treatment with B. trimera was able to decrease oxidative damage as well as improve antioxidant defense. There was also a decrease in inflammation, collagen area and hemorrhage. All the beneficial effects promoted by carqueja were similar to those found by the positive controls used in our study (vitamin C and omeprazole). Analyzing our data, we can conclude that B. trimera presents a gastroprotective effect and should be further studied for its application in gastric ulcer therapy. After 2 days of consumption of absolute ethanol, the animals' stomachs showed an increase in oxidative stress, characterized by reduction of oxidized glutathione (GSSG) and increase of TBARS and carbonylated protein. This situation led to stomach inflammation, necrosis, hemorrhage and hyperemia. These was minimized by the consumption of Baccharis trimera extracts (Bt), since it was able to decrease oxidative damage and increasing GSSG, reduced glutathione (GSH) and catalase (CAT). In addition, there was decreased inflammation, hemorrhage and collagen area after Bt consumption. GR reductase gluthione, GPx peroxidase glutathione. Bt in green: stimulation; Bt in red: inhibits.

Pre-protective effect of polysaccharides purified from Hericium erinaceus against ethanol-induced gastric mucosal injury in rats

The β-glucan H6PC20 (Mw: 2390 kDa) and α-heteropolysaccharide HPB-3 (Mw: 15 kDa) were purified from the fruiting body of Hericium erinaceus according to the previous methods. Their gastroprotective activities and corresponding structure-activity relationship were studied in the ethanol-induced gastric ulcer model of rats. After intragastric administrated with H6PC20 and HPB-3 for 14 days, macroscopic and histological evaluation of gastric mucosa was improved significantly. The defense and repair factors (EGF, bFGF and PGE2) were increased, meanwhile, the inflammatory cytokines (IL-1β and TNF-α) and MDA were reduced. These results indicated that H6PC20 and HPB-3 presented gastroprotective activities with the mechanism of activating repair and defense system, decreasing the inflammatory response and alleviating the oxidative injury. Furthermore, the structure-activity relationship showed that the macromolecular β-glucan was better for repair and defense system, while the low weight molecular α-heteropolysaccharide focused on the anti-inflammatory effect. The polysaccharides purified from H. erinaceus can be developed as a potential gastroprotective ingredient for applications in pharmaceutical field.

Fisetin attenuates gastric mucosal lesions through modulating nuclear factor-kappa B and peroxisome proliferator-activated receptor-γ in rats

Background: Nowadays, the use of plant extracts is increasing in the world for the prevention and treatment of ulcer. Objective: The objective of this study was to explore the underlying mechanism of action of fisetin on ethanol-induced gastric ulcer model. Materials and Methods: In this study, gastric mucosal lesions were induced by ethanol in rats. Five groups of rats were formed based on the treatment administered: model group (model), omeprazole (40 mg/kg) group (omeprazole), high-dose fisetin group (100 mg/kg, H-fisetin), medium-dose fisetin group (50 mg/kg, M-fisetin), and low-dose fisetin group (25 mg/kg, L-fisetin). Interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α levels were assessed in serum. The expression of peroxisome proliferator-activated receptor (PPAR)-γ, nuclear factor-kappa B (NF-κB), and p38-mitogen-activated protein kinase (p38-MAPK) in the gastric mucosa was also measured. Results: In the case of the high-dose fisetin group, the level of TNF-α, IL-1β, and IL-6 decreased from 9.57 pg/mL to 5.19 pg/mL, from 0.59 pg/mL to 0.27 pg/mL, and from 37.96 pg/mL to 21.09 pg/mL, respectively. In the case of the omeprazole group, the level of TNF-α, IL-1β, and IL-6 decreased to 4.38 pg/mL, 0.27 pg/mL, and 18.58 pg/mL, respectively. The expression of PPAR-γ protein in the high-dose fisetin and omeprazole groups was about 1.5 times higher than that in the model group. Compared with the model group, the expression of NF-κB protein reduced to 0.34 level and 0.47 level in the omeprazole and high-dose fisetin groups, respectively. Compared with the model group, the expression of p38-MAPK protein reduced to 0.55 level and 0.68 level in the omeprazole and high-dose fisetin groups, respectively. Conclusion: Fisetin might relieve the symptoms of ethanol-induced gastric ulcer in rats through the regulation of NF-κB pathway.

Gastric ulcer healing activity against acidified ethanol-induced gastric ulcer and gastroprotective mechanisms of Zingiber simaoense rhizome ethanol extract in rats

Background: Zingiber simaoense Y. Y. Qian (Zingiberaceae) rhizomes have been widely used to alleviate gastric disorders in Thai traditional medicine. Objectives: This study aimed to investigate the gastric ulcer healing activity of Z. simaoense rhizome ethanol extract (ZSE) against acidified ethanol-induced gastric ulcer and its possible gastroprotective mechanisms. Materials and Methods: The gastric ulcer healing activity of ZSE was evaluated using an acidified ethanol-induced gastric ulcer model in rats. The involvement of endogenous nitric oxide (NO) and sulfhydryl (SH) compounds in ZSE gastroprotection was also examined in addition to the determination of NO, malondialdehyde (MDA), and prostaglandin (PG) E2levels in rat gastric tissues as well as the determination of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and total phenolic content in ZSE. Results: ZSE at the dose of 240 mg/kg/day significantly accelerated gastric ulcer healing when observed on days 4 and 8 following ulcer induction. Pretreatment with either NG-nitro-L-arginine methyl ester or N-ethylmaleimide inhibited the gastroprotective activity of ZSE. Moreover, ZSE significantly increased NO and PGE2levels and decreased MDA levels in rat gastric tissues. DPPH radical scavenging activity and total phenolic compounds were also presented in ZSE. Conclusion: This study demonstrates the gastric ulcer healing activity of ZSE against acidified ethanol-induced gastric ulcer in rats. The possible gastroprotective mechanisms underlying the cytoprotective effect of ZSE might also involve gastric mucosal NO, SH compounds, and PGE2as well as its antioxidant activities.

Effectiveness of Opuntia ficus indica L. inermis Seed Oil in the Protection and the Healing of Experimentally Induced Gastric Mucosa Ulcer.

Gastric ulcer is a painful lesion of the gastric mucosa which can be disabling, or even more very serious in the case of a perforation of the stomach and internal hemorrhage. Traditional pharmacopeias have shown the efficacy of various plant extracts in the treatment of this pathology. Some extracts from Opuntia ficus indica (OFI) have been proven to have medicinal therapeutic benefits. The aim of this study was to investigate the preventive and curative effects of OFI seed oil extracted by cold pressing on an ethanol-induced gastric ulcer model in rats. Gastroprotective activities of the oil were assessed as pretreatments prior to ethanol gavage of Wistar rats compared to reference drugs. Two oil dose effects were tested. Ulcer and gastric parameters were measured (ulcerated areas (mm2), % of ulcer inhibition, gastric juice volume and pH, and mucus weight). Macroscopical and microscopical assessments of the stomachs as well as gastric biopsy histological studies were carried out. OFI oil exhibited a high efficiency in the protection of the cytoarchitecture and function of the gastric mucosa against the severe damages provoked by ethanol intake. Ulcerated areas were very significantly reduced and the % of ulcer inhibition was the highest under OFI oil pretreatment. Mucus production was stimulated, gastric juice volume was reduced, and its pH was increased. Histopathological examination of H&E-stained biopsies collected from gastric mucosae from the different experimental groups confirmed the gastroprotective efficacy of OFI oil against ethanol-induced symptoms such as inflammation and damages like bleeding, erosions, lesions, necrosis, and ulcers. Furthermore, OFI oil treatment speeded-up the reduction of the surface of ethanol-induced ulcerated areas in a dose-dependent manner, leading to a time gain in the healing process. The healing rate reached 91% on day 2 and 99% on day 3, and a complete heal was attained at the fourth day under OFI oil treatment, while ulcer areas were still partially unhealed in all the other groups. The therapeutic effects of OFI oil against gastric ulcer could be mediated by its varied bioactive compounds that we have demonstrated in the analytical study. They could act synergistically or in a delayed manner to optimize the healing process through protective antioxidant properties, as well as an antagonism against histamine H2-receptors, a stimulation of the signaling pathways necessary for mucus and bicarbonate production, and reduction of inflammatory processes in the gastric mucosa. Additionally, OFI oil fatty acids (especially unsaturated) and triacylglycerols contribute to the reconstruction and the repair of the cell membrane lipid bilayer during the gastric ulcer healing process.

Gastroprotective effects of ursolic acid isolated from Ochrosia elliptica on ethanol-induced gastric ulcer in rats

The prevention of gastric ulcer pathogenesis or its recurrence is currently one of the main goals of clinical and experimental studies. This study was conducted to investigate the gastroprotective effects of ursolic acid (UA) isolated from the dichloromethane/methanol extract of shoots of Ochrosia elliptica Labill. and investigated for its activity against an ethanol-induced gastric ulcer model in rats. Fifty-six female albino rats were divided into seven groups (eight rats per group): The first group served as control; group 2: absolute ethanol group (5 ml/kg. b.w.); group 3: ranitidine pretreated group (50 mg/kg, i.p.); group 4: UA (100 mg/kg, b.w.); and groups from 5 to 7 were pretreated with UA (25, 50, and 100 mg/kg, b.w.). Then, all animals were sacrificed, and the stomachs were excised for examination. Gastric mucosal injuries were assessed by gross examination, histopathology, immunohistochemistry of caspase-3, and biochemical parameters, including tissue malondialdehyde (MDA) and total antioxidant capacity (TAC) levels. The ethanol group showed severe mucosal injury compared with UA-treated animals, which grossly showed significant reductions of ulcer areas. Histopathologically, they showed marked reductions of mucosal necrosis, edema, and leukocyte infiltrations. Significant increased TAC levels were associated with reduced MDA levels UA-treated rats. In addition, the caspase-3 activity was downregulated. These findings indicated gastroprotective effects of UA at the administered doses comparable with that observed with the control drug ranitidine through suppression of mucosal oxidative stress and antiapoptotic activities. Molecular docking studies showed that UA binds to H+/K+ ATPase more than omeprazole and ranitidine −9.23 vs. −7.09 and 6.29 kcal/mol). In addition, the pKi value of UA was also lower than omeprazole and ranitidine (169.6 nM vs. 6.3 and 26.7 µM). The molecular docking findings suggested the protection role of UA against ethanol-induced gastric ulcer.

Gastroprotective effects of Erythrina speciosa (Fabaceae) leaves cultivated in Egypt against ethanol-induced gastric ulcer in rats.

Members of the genus Erythrina have been traditionally used in the treatment of various ailments such as inflammation and gastrointestinal disorders. Erythrina speciosa (Fabaceae) is a spiny, deciduous shrub or small tree native to Southern America in Brazil. It is cultivated in Africa and Asia. The traditional usage of E. speciosa indicated its antibacterial, analgesic, and anti-inflammatory activities. Evaluation of the phytochemical constituents, gastroprotective effects and possible mechanism of action of the ethyl acetate fraction obtained from the methanol extract of E. speciosa leaves (ESLE). Chemical characterization of ESLE was done using high performance liquid chromatography coupled to mass spectrometry (HPLC-MS). The gastroprotective activity of ESLE was evaluated using ethanol-induced gastric-ulcer model in rats. Rats were pre-treated with ESLE 25, 50 and 100 mg/kg 1 h before the administration of absolute ethanol. Histological analysis, mucin content, and total acidity were evaluated. The possible mechanism of action of ESLE was studied through the examination of oxidative stress and inflammatory markers, PGE2, and NF-κB, iNOS, COX-2, and HSP-70 immunoexpression. In vitro, anti-Helicobacter pylori activity of ESLE was also studied using micro-well dilution method. Fourteen compounds were tentatively identified including alkaloids, flavonoids, and saponins. ESLE exerted a powerful gastroprotective effect. The pre-treatment with ESLE at different doses resulted in a significant reduction in gastric lesions and significant elevation in the mucin production. These effects could be partially mediated by the potent anti-inflammatory activity of ESLE as evidenced by the significant reduction in the immunoexpression of NF-κB, COX-2, iNOS and the reduction in the pro-inflammatory marker, TNF-α. ESLE counteracted the ethanol-induced oxidative stress by increasing the levels of depleted GSH and catalase as well as significantly attenuating the ethanol-induced lipid peroxidation tissue levels. In addition, ESLE exhibited in vitro antibacterial activity against H. pylori. The chemical constituents of ESLE strongly support its potent gastroprotective effect suggesting its future potential application in the management of gastric ulcer by eliminating its symptoms and causes including H. pylori.

Gastroprotective effect of cilostazol against ethanol- and pylorus ligation-induced gastric lesions in rats.

Despite the availability of effective antiulcer medications, their suboptimal safety profile ignites the search for alternative/complementary treatments. Drug repositioning is an attractive, efficient, and low-risk strategy. Cilostazol, a clinically used phosphodiesterase 3 inhibitor, has pronounced anti-inflammatory and vasodilatory effects suggesting antiulcer activity. Using ethanol-induced and pyloric ligation-induced gastric ulcer models, we investigated the gastroprotective effect of cilostazol (5 or 10mg/kg, p.o.) in comparison with the standard antiulcer ranitidine (50mg/kg, p.o.) in rats. Gastric mucosa was examined macroscopically, histologically, and biochemically for ulcer severity, markers of oxidative stress, proinflammatory cytokines, apoptotic, and cytoprotective mediators. Gastric acidic output, peptic activity, and mucin content were measured in gastric fluids. Pretreatment with cilostazol reduced ulcer number and severity, ameliorated redox status (reduced glutathione and malonaldehyde content), and decreased levels of IL-1β, IL-6, and TNF-훼 in gastric mucosa, in parallel with increases in mucosal defensive factors nitric oxide (NO), prostaglandin E2 (PGE2), and heat-shock protein 70 (HSP70) promoting mucus secretion, tissue perfusion, and regeneration. Histological examination confirmed the beneficial effects of cilostazol in terms of reducing focal necrosis and infiltration of inflammatory cells, as well as increasing mucopolysaccharide content. These beneficial effects are likely secondary to an increase in cAMP and decrease in apoptosis regulator Bcl-2-associated X protein (BAX). Cilostazol, in a dose-dependent effect, exhibited vasodilatory, anti-inflammatory, and antiapoptotic actions in the gastric mucosa resulting in significant antiulcer activity comparable with the standard drug, ranitidine, but devoid of antisecretory activity. Therefore, its use should be dose and ulcer-inducer dependent.

The histochemical and biochemical effects of coconutmilk in Wistar rats with ethanol-induced gastric ulcer

This study aimed at investigating the histochemical and biochemical effects of coconut milk in Wistar rats’ model of ethanol-induced gastric ulcer with a view to evaluating the antiulcerogenic potential of coconut milk in the management of gastric ulcer. Thirty male Wistar rats weighing between 150-180g were recruited for the study and divided into six groups of 5 rats each. All the groups were fasted for 24-hours after which group-1 received single oral administration of normal saline at 5ml/kg, while groups 2-6 received equivalent amount of ethanol. Twenty-four hours later, Groups-3, 4, 5 received oral graded doses of coconut milk at 30, 50, 70 mg/kg respectively while group 6 received omeprazole administration at 10 mg/kg every 12-hours for a period of 21 days. The ulcer index as well as Prostalglandin-E2 and Nitric Oxide concentrations was significantly (p < 0.05) lowered following treatment with omeprazole and coconut milk, when compared with the ethanol group. Coconut milk administration also attenuated the ethanol-induced histochemical distortions of the gastric pylorus. This study concluded that coconut milk administration ameliorated ethanol-induced gastric ulcer and serves as a potential choice in the treatment of the condition.Keywords: Gastric ulcer, Ethanol, Coconut Milk, Omeprazole, Histochemical, Biochemical

Potential Gastroprotective Activity of Rice Bran (Oryza sativa L.) Extracted by Ionic Liquid-Microwave-Assisted Extraction against Ethanol-Induced Acute Gastric Ulcers in Rat Model.

The presence of gamma-oryzanol in rice bran oil can be 10⁻20-fold higher than tocopherol and tocotrienol. Gamma-oryzanol has various pharmacological properties. The objective of this study was to evaluate the effectiveness of rice bran extract as a gastroprotective in reducing lesions in ethanol-induced acute gastric ulcer models in rat, using the ionic liquid-microwave-assisted extraction (IL-MAE) method. Rice bran extract was obtained using the IL-MAE method with ionic liquid (IL), 1-butyl-3-methylimidazolium tetrafluoroborate [BMIM]BF₄ (concentration 0.7 M), and a ratio of solid/liquid of 15 g/mL, 15 min extraction time, and 10% microwave power. The rats were pretreated with rice bran extract at different doses (100, 200, and 400 mg/kg body weight; BW) for seven days and subsequently exposed to acute gastric lesions induced by 80% ethanol. Omeprazole (36 mg/kg BW) was used as a standard anti-ulcer drug. The ulcer index, gastric juice acidity, and mucus levels were measured to assess the degree of gastroprotection. The results showed that the oral administration of rice bran extract at a dose of 400 mg/kg BW significantly inhibited the development of ulcer formation by 66.75% and reduced gastric acid levels. Moreover, gamma oryzanol and omeprazole protected the gastric mucosa from ethanol-induced gastric lesions by increasing the level of gastric mucus. Rice bran extract is effective as a gastroprotective therapy sourced from natural ingredients in treating the incidence of gastric ulcers. Most likely, this is related to gamma oryzanol as a bioactive compound contained in rice bran (Oryza sativa L.).