Gastric Lesion Model Research Articles

Chemical characterization of the essential oil from the leaves of Eugenia flavescens DC. (Myrtaceae) and its potential in the treatment of pain, inflammation, and ethanol- and ethanol/HCL-induced gastric ulcers in mice.

Eugenia flavescens is a species cultivated in Brazil for food purposes. Given the potential application of essential oils from plants of the genus Eugenia, this study was carried out to investigate the chemical composition, acute toxicity, antioxidant, antinociceptive, gastroprotective activities, and possible mechanisms of action of the essential oil from the leaves of E. flavescens (EOEf). The EOEf was extracted by hydrodistillation, and the chemical composition was obtained using gas chromatography-mass spectrometry. The antioxidant activity was evaluated, as well as the acute toxicity and the antinociceptive and anti-inflammatory effects in mice. In addition, the gastroprotective effect was investigated using an acute gastric lesion model, considering possible mechanisms of action. The major components found in the EOEf were guaiol (19.97%), germacrene B (12.53%), bicyclogermacrene (11.11%), and E-caryophyllene (7.53%). The EOEf did not cause signs of toxicity in the acute oral toxicity test and showed in vitro antioxidant activity with IC50 ranging from 247.29 to 472.39µg/mL in the tests ABTS and DPPH. In the nociceptive test, EOEf showed a 72.05% reduction in nociception at a dose of 100mg/kg. In evaluating the anti-inflammatory effect, the essential oil inhibited paw edema by 95.50% and 97.69% at doses of 50 and 100mg/kg. The results showed that EOEf has a gastroprotective effect, acting through the sulfhydryl compounds (-SH), nitric oxide (NO), and synthesis PGE2 pathways. The results suggested that EOEf is a promising source of constituents with antioxidant, antinociceptive, anti-inflammatory, and gastroprotective properties with application in the food and pharmaceutical industries.

Synergistic Antinociceptive Effect of β-Caryophyllene Oxide in Combination with Paracetamol, and the Corresponding Gastroprotective Activity.

Pain is the most frequent symptom of disease. In treating pain, a lower incidence of adverse effects is found for paracetamol versus other non-steroidal anti-inflammatory drugs. Nevertheless, paracetamol can trigger side effects when taken regularly. Combined therapy is a common way of lowering the dose of a drug and thus of reducing adverse reactions. Since β-caryophyllene oxide (a natural bicyclic sesquiterpene) is known to produce an analgesic effect, this study aimed to determine the anti-nociceptive and gastroprotective activity of administering the combination of paracetamol plus β-caryophyllene oxide to CD1 mice. Anti-nociception was evaluated with the formalin model and gastroprotection with the model of ethanol-induced gastric lesions. According to the isobolographic analysis, the anti-nociceptive interaction of paracetamol and β-caryophyllene oxide was synergistic. Various pain-related pathways were explored for their possible participation in the mechanism of action of the anti-nociceptive effect of β-caryophyllene oxide, finding that NO, opioid receptors, serotonin receptors, and K+ATP channels are not involved. The combined treatment showed gastroprotective activity against ethanol-induced gastric damage. Hence, the synergistic anti-nociceptive effect of combining paracetamol with β-caryophyllene oxide could be advantageous for the management of inflammatory pain, and the gastroprotective activity should help to protect against the adverse effects of chronic use.

Novel beagle model of gastric local fibrotic target lesions for the evaluation and training of endoscopic techniques

BackgroundNovel endoscopic techniques used in the treatment of gastric lesions with local submucosal fibrosis need preclinical evaluation and training due to safety limitations. Therefore, the purpose of our study was to establish an animal model of gastric local fibrotic target lesions and assess its feasibility in the evaluation and training of endoscopic techniques.MethodsIn six experimental beagles, a 50% glucose solution was injected into three submucosal areas of the fundus, body, and antrum of the stomach to create gastric local fibrotic target lesions (experimental group). On post-injection day (PID) 7, the injection sites were assessed endoscopically to confirm the presence of submucosal fibrosis formation, and the dental floss clip traction assisted endoscopic submucosal dissection (DFC-ESD) procedure was performed on the gastric local fibrotic target lesions to confirm its feasibility after endoscopic observation. The normal gastric mucosa of six control beagles underwent the same procedure (control group). All the resected specimens were evaluated by histological examination.ResultsAll 12 beagles survived without postoperative adverse events. On PID 7, 16 ulcer changes were observed at the injection sites (16/18) under the endoscope, and endoscopic ultrasonography confirmed the local submucosal fibrosis formation in all ulcer lesions. The subsequent DFC-ESD was successfully performed on the 32 gastric target lesions, and the mean submucosal dissection time in the ulcer lesions was greater than that in the normal gastric mucosa (15.3 ± 5.6 vs. 6.8 ± 0.8 min; P < 0.001). There was no difference in rates of en bloc resection, severe hemorrhage, or perforation between the two groups. Histological analysis of the ulcer lesions showed the absence of epithelial or muscularis mucosae and extensive submucosal fibrous tissue proliferations compared with normal gastric mucosa. Overall, endoscopists had high satisfaction with the realism and feasibility of the animal model.ConclusionWe developed a novel animal model of gastric local fibrotic target lesions to simulate difficult clinical situations, which strongly appeared to be suitable for the preclinical evaluation and learning of advanced endoscopic techniques.

Gastroprotection of Riparin III in the Acute Model of Ethanol-Induced Gastric Lesion in Mice

Gastroprotection of Riparin III in the Acute Model of Ethanol-Induced Gastric Lesion in Mice

Ximenia americana L.: Chemical Characterization and Gastroprotective Effect

Ximenia americana L., popularly known in Brazil as “ameixa do-mato, ameixa-brava, and ameixa-do-sertão,” is widely used in folk medicine to treat several intestinal disorders. The present study assessed the potential mechanisms of action underlying the gastroprotective activity of the hydroethanolic extract of Ximenia americana L. (EHXA) stem bark. The acute toxicity of EHXA was estimated, and later, the gastroprotective effect in mice was assessed through acute models of gastric lesions induced by acidified or absolute ethanol and indomethacin, where the following mechanisms were pharmacologically analyzed: the involvement of prostaglandins (PG), histamine (H2) receptors, ATP-dependent potassium channels, sulfhydryl groups (SH), α2 adrenergic receptors, nitric oxide (NO), myeloperoxidase (MPO), gastric mucus production, and acetylcholine-mediated intestinal motility. Regarding toxicity, EHXA did not cause deaths or signs of toxicity (LD50 greater than or equal to 2000 mg/kg/p.o.). When the gastroprotective effect was assessed, EHXA (50, 100, and 200 mg/kg/p.o.) reduced the rate of lesions induced by acidified ethanol by 65.63; 53.66, and 58.02% in absolute ethanol at 88.91, 78.82, and 74.68%, respectively, when compared to the negative control group. In the indomethacin-induced gastric injury model, the reductions were 84.69, 55.99, 55.99, and 42.50%, respectively. The study revealed that EHXA might stimulate mucus production and reduce intestinal motility through SH groups, NO production, and activation of α2 adrenergic receptors. The results indicated that EHXA had significant gastroprotective activity in the evaluated models. However, further investigation is required to elucidate the cellular and molecular events underlying the action of EHXA components and to correlate them with the modulation of the signaling pathways, as demonstrated by the current pharmacological approach. Therefore, the results demonstrated in the present study, as well as previously reported findings, support the recommendation of using this species in traditional communities in Brazil.

Phenolic-rich extract of Nopalea cochenillifera attenuates gastric lesions induced in experimental models through inhibiting oxidative stress, modulating inflammatory markers and a cytoprotective effect.

Nopalea cochenillifera (Cactaceae), popularly known as "palma" or "palma doce", is from Mexico, but it was widely introduced in Brazil through crops. It has been used as food and in traditional medicine and is a good source of phenolic compounds. In this study the phytochemical profile and gastroprotective activity of phenolic-rich extract of N. cochenillifera in acute gastric lesion models induced by ethanol and indomethacin were evaluated. High-performance liquid chromatography coupled with mass spectrometry (HPLC/ESI/MSn) allowed the characterization of 12 compounds such as sugars, phenolics and flavonoids. Among polyphenols, the main peak was assigned to isorhamnetin-3-O-(2'',3''-O-di-rhamnose)-glucoside. The TPC and TFC in the dry extract were 67.85 mg of gallic acid equivalent per g/extract and 46.16 mg quercetin equivalent per g/extract, respectively. In the in vitro MTT assay, the extract showed no cytotoxicity and suppressed ROS levels in LPS-treated RAW 264.7 cells. Preclinical models in rats showed that a dose of 100 mg kg-1 (p < 0.0001) in the ethanol model and doses of 100 mg kg-1 (p < 0.5) and 200 mg kg-1 (p < 0.01) in the indomethacin model reduced the gastric lesions. Also, the extract reduced the MPO, MDA, TNF-α and IL-1β levels and increased the GSH and IL-10 levels. The pre-treatment with the extract led to the upregulation of SOD and the downregulation of COX-2 by immunohistochemical analysis. It also showed a cytoprotective effect in the histopathological analysis and stimulated the restoration of the mucus content as observed in the periodic acid-Schiff analysis without modifying the pH, volume or total acidity of the gastric juice. Taken together, N. cochenillifera extract can be applied as a novel gastroprotective ingredient for food or pharmaceutical products.

Gastroprotective effect methanol extract of Caesalpinia coriaria pods against indomethacin- and ethanol-induced gastric lesions in Wistar rats

Ethnopharmacological relevanceCaesalpinia coriaria (Jacq.) Willd is widely used as a traditional medinal plant in Mexico for protective and healing purposes and the treatment of gastrointestinal diseases. Aim of the studyTo investigate the gastroprotective effect of extract of Caesalpinia coriaria pods against ethanol-induced and indomethacin-induced gastric lesion models, its anti-inflammatory and antioxidative activities, and its main compounds through LC-MS analysis. Materials and methodsMale Wistar rats were orally administered a methanol extract obtained from the pods of C. coriaria at doses of 10, 30, 100, and 300 mg/kg prior to inducing gastric lesions with ethanol or indomethacin. Gastric mucosal lesions were evaluated by macroscopic and histopathological alterations. Determination of prostaglandin E2 (PGE2), alpha tumor necrosis factor (TNF-α), leukotriene B4 (LTB4), nitrites/nitrates, superoxide dismutase (SOD), and H2S gastric levels were investigated. Its main compounds of the active extract through LC-MS analysis. ResultsPhenolic compounds were identified as major components of methanol extract. LC-MS analysis identified 15 constituents, and the significant compounds were gallic acid, 3-O-galloylquinic acid, digalloylglucose, tetragalloylglucose, valoneic acid dilactone, pentagalloylglucose, digalloylshikimic acid, and ellagic acid. Pretreatment with the extract at doses of 100 and 300 mg/kg significantly reduced gastric ulcer lesions in both models. Compared with the reference drugs (omeprazole or ranitidine, respectively), no significant difference was found (p < 0.05). The extract's gastroprotective effect was accompanied by significant decreases in leukocyte recruitment, and gastric levels of TNF-α and LTB4 by two to fourfold (p < 0.05). Also, gastric levels of PGE2 gastric levels were maintained and the antioxidant enzyme activities of SOD and nitrate/nitrite in the gastric tissue were improved (p < 0.05). The LC-MS analysis indicated the presence of hydrolyzable tannins (mainly gallic acid derivatives). ConclusionThe results suggest that the gastroprotective effect of the methanol extract of C. coriaria pods occurs through anti-inflammatory, antioxidant, and NO modulation properties, and gallic acid derivatives may be the main possible compounds responsible for its actions.

Antiulcerogenic and healing activity of hecogenin acetate in rodents.

Peptic ulcers are lesions in the gastric and duodenal mucosa generated by an imbalance between protective factors (gastroduodenal mucus secretion, bicarbonate production, adequate blood flow) and harmful factors (excess pepsin or hydrochloric acid). Some drugs used in peptic ulcer therapy are associated with adverse effects. The aim of this study was to evaluate the antiulcerogenic and healing activity of hecogenin acetate (HA) in acute and chronic models of gastric lesions in rodents. The antiulcerogenic activity of HA was evaluated in models of gastric lesions induced by absolute ethanol and in acidified ethanol with HA (5, 10, and 20mg/kg). For the model of gastric lesions induced by ischemia and reperfusion, rats were pre-treated with HA (5, 10, 20mg/kg). After that, they were submitted to 30min of ischemia, followed by 1h of reperfusion. To evaluate the healing activity was induced gastric ulcer using acetic acid (80%) in rats. After 24h, they were treated for 7 consecutive days with HA (10 and 20mg/kg). They were evaluated the possible signs of toxicity, measurement of the lesions, collagen deposition, and histological analysis. HA significantly reduced the area of the lesion in models of gastric lesions induced by absolute and acidified ethanol, ischemia-induced gastric lesions and reperfusion, and regarding healing. In the collagen deposition, the presence and increase of collagen demonstrate the healing effect. The AH has antiulcerogenic and healing potential demonstrated by the decrease in gastric injury and presence of collagen fibers, respectively.

COMPARATIVE CHARACTERISTICS OF ANTIULCER ACTIVITY OF PLACENTAL CRYOEXTRACT UNDER DIFFERENT MODES OF APPLICATION IN THE EXPERIMENT

Peptic ulcer disease is one of the most common diseases of the gastrointestinal tract worldwide. Among the causes of disability in the adult population, diseases of the digestive tract occupy the 5th place, and about 20.0–30.0% of them is peptic ulcer disease, which leads to permanent disability in more than 50.0% of patients. According to scientific reports, the prevalence of this pathology is due to its polyetiology, which leads to clinical heterogeneity and recurrent course. The aim of this study is to conduct a comparative assessment of the antiulcer effect of placental cryoextract in prophylactic, therapeutic and therapeutic-prophylactic regimens in models of ethanol-prednisolone gastric lesions. The study was performed on 84 nonlinear laboratory male rats weighing 200–220 g. To simulate damage to the gastric mucosa, rats were administered a single ethanol-prednisolone mixture: prednisolone (20 mg/kg) dissolved in 80.0% ethyl alcohol (0.6 ml / 100 g of animal body weight). The rats were killed in 24 h after the administration of ethanol-prednisolone mixture. The drug "Cryocell-cryoextract of the placenta" was used in three modes: for prophylactic purpose – once a day for 5 days before the ethanol-prednisolone administration; for therapeutic purpose – once in 60 min after the administration of ethanol-prednisolone mixture; for the therapeutic and prophylactic purposes – once in 3 days before the administration of ethanol-prednisolone mixture and 60 min following the administration of ethanol-prednisolone mixture. The effect of the studied drug on the condition of the gastric mucosa was assessed macroscopically by L. V. Yakovleva scale. Macroscopic evaluation of the gastric mucosa showed that after 24 h following the administration of the ethanol-prednisolone mixture, the severity of damage averaged 3.7±0.37 points out of the five maximal points, and the ulcer index was 3.9 SU, respectively. The prophylactic five-day administration of esomeprazole resulted in an antiulcer activity in 45.9% of cases that was 1.8 times lower than that of the cryoextract rats. Erosive-ulcerative lesions of the gastric mucosa under the therapeutic-and-prophylactic modes of placental cryoextract were observed in only 28.6% of rats that corresponded to the value of the ulcer index equalled 0.3 units, and antiulcer activity was 92.3%. Under this regimen, the antiulcer activity of the cryoextract was practically comparable to the efficacy of esomeprazole (97.4%). Conclusion. The administration of cryoextracted placenta for the therapeutic purpose (once after ethanol-prednisolone mixture) is accompanied by the lowest antiulcer activity that was 22.2% and in 4.1 times lower than the effectiveness of esomeprazole. Therapeutic and prophylactic application of cryoextracted placenta led to a statistically significant (p&lt;0.05) attenuation of the damaging effects of ethanol-predniolone mixture, and antiulcer activity was 92.3%, respectively.

Proteomics and Metabolomics Unveil Codonopsis pilosula (Franch.) Nannf. Ameliorates Gastric Precancerous Lesions via Regulating Energy Metabolism.

Objective: This study aimed to systematically evaluate the efficacy of Codonopsis pilosula (Franch.) Nannf. (Codonopsis Radix, CR) and reveal the mechanism of its effects on suppressing Gastric Precancerous Lesions. Methods: First, we established the GPL rat model which was induced by N-methyl-N′-nitro-N-nitrosoguanidine, a disordered diet, and 40% ethanol. The CR’s anti-Gastric Precancerous Lesions effect was comprehensively evaluated by body weight, pathological section, and serum biochemical indexes. Then, quantitative proteomics and metabolomics were conducted to unveil the disturbed protein-network and pharmacodynamic mechanism. Furthermore, serum pharmacology was employed to confirm that CR’s anti-gastritis and anti-cancer phenotype in cell models. Results: In animal models, CR had been shown to control inflammation and ameliorate Gastric Precancerous Lesions. Considering the combination of proteomics and metabolomics, we found that CR could significantly reverse the biological pathways related to energy metabolism which were disturbed by the Gastric Precancerous Lesions model. Furthermore, the results of serum pharmacology indicated that the Codonopsis Radix containing serum could ameliorate gastritis injury and selectively inhibit the proliferation of gastric cancer cells rather than normal cells, which was closely related to ATP production in the above mentioned cells. Conclusion: In summary, CR exerted anti-Gastric Precancerous Lesions effects by ameliorating gastritis injury and selectively inhibiting the proliferation of gastric cancer cells rather than normal cells. Proteomics and metabolomics unveiled that its efficacy was closely related to its regulation of the energy-metabolism pathway. This research not only provided new ideas for exploring the mechanism of complex systems such as Chinese herbals but also benefited the treatment strategy of Gastric Precancerous Lesions via regulating energy metabolism.

EVALUATION OF ANTIULCEROGENIC EFFECT OF CRYOCONSERVATED PLACENTA EXTRACT ON THE MODEL OF ETHANOL-PREDISONOLIC LESIONS OF THE GASTRIC MUCOSA

Relevance. Gastric and duodenal ulcers occur in 6-10% of the adult population, and mortality from peptic ulcers ranges from 5 to 15%. Conservative treatment of this disease almost always involves the use of antisecretory and antibacterial drugs. Existing treatment regimens for peptic ulcer disease, focused on key pathogenetic mechanisms, do not take into account the individual adaptive and trophological characteristics of patients. As a potential antiulcer agent, our attention was drawn to the cryopreserved placenta extract ("Cryocell-cryoextract placenta"). It eliminates the ulcerogenic effect of anti-inflammatory drugs of non-steroidal nature, without affecting their therapeutic efficacy.&#x0D; Objective: to characterize the anti-ulcerogenic effect of therapeutic and prophylactic use of cryopreserved placenta extract in the model of alcohol-prednisolone gastric lesions in rats.&#x0D; Methods. The study was performed on 28 male rats weighing 200-220 g. they were randomized into four groups: I (n = 7) – intact rats, II (n = 7) – control – rats with model pathology (alcohol-prednisolone gastric lesion) without treatment, III (n = 7) – rats with alcohol-prednisolone gastric lesions, which were injected with cryoextract placenta (0.16 ml / kg body weight, intramuscularly), IV (n = 7) – rats with alcohol-prednisolone gastric lesions, which were administered the reference drug esomeprazole, proton pump inhibitor (50 mg / kg , intragastric). Gastric lesions in rats were simulated by intragastric single administration of prednisolone (20 mg/kg) dissolved in 80.0% ethanol (0.6 ml/100 g body weight). Cryoextracts of the placenta were administered intravenously in a prophylactic mode – 1 time per day for 4 days before and 1 time 60 minutes after the introduction of ethanol-prednisolone mixture. In 24 h. after administration of the mixture, rats were removed from the experiment and the size of the stomach (bloating) and the presence of adhesions with adjacent organs were evaluated macroscopically by the following criteria: erosions and hemographies, hyperemia, edema and mucosal fold disorders. For each group, the percentage of experimental animals was calculated according to these characteristics and the average value of their severity. The values ​​of the ulcer index were calculated for each group.&#x0D; Results. The study showed that the introduction of placental cryoexact as well as the reference drug esomeprazole led to a statistically significant (p&lt;0.05) reduction of three times the prevalence of gastric ulcers in rats after administration of alcohol-prednisolone mixture. The use of placental cryoextract in the treatment-and-prophylactic regimen led to a statistically significant (p&lt;0.05) decrease in the value of the ulcer index in 13 times relative to the control rats, and the average score of macroscopic assessment of gastric mucosa was 3.5 times lower and was 1.1±0.24 and 3.9±0.26, respectively. In animals treated with esomeprazole 2 times more moderate (2 [0.5; 3] points) hyperemia of the central nervous system (57.1% and 28.6%, respectively) and several times more moderate (2 [0; 2]). points) edema of the secondary school. In addition, edema of the central nervous system in rats administered esomeprazole led to a clear (3 [2; 3] points) violation of the folding of the central nervous system in 71.4% of rats. In contrast to the use of esomeprazole, placental cryoextract more significantly leveled the hyperemia induced by the introduction of alcohol-prednisolone mixture and edema of the gastric mucosa, which were observed in only 28.6% and 14.3% of rats, respectively.&#x0D; Conclusions. Therapeutic and prophylactic use of placental cryoextract was accompanied by statistically significant (p &lt;0.05) comparable to esomeprazole antiulcer efficacy in the model of ethanol-prednisolone gastric lesion and amounted to 92.3%.

Гастропротективна дія кріоконсервованого екстракту плаценти за профілактичного режиму застосування

Introduction. Timely treatment and prevention of peptic ulcer of the stomach and duodenum is not only medical but also social. As a potential gastroprotective agent, our attention was drawn to the cryopreserved extract of human placenta, because the literature convincingly demonstrated that this cryoextract eliminates the ulcerogenic action of nonsteroidal anti-inflammatory drugs, which has a mechanism similar to peptic ulcer disease. The aim of the study was to characterize the gastroprotective activity of cryopreserved placenta extract under the prophylactic regimen of use in the model of ethanol-prednisolone gastric lesions in rats. Materials and methods. The study was performed on 28 male rats weighing 200–220 g. Gastric lesions in rats were simulated by intragastric single administration of prednisolone (20 mg/kg) dissolved in 80.0% ethanol (0.6 ml/100 g body weight). Cryoextracts of the placenta were administered intravenously in a prophylactic mode – 1 time per day for 5 days before the introduction of ethanol-prednisolone mixture. In 24 h. after administration of the mixture, rats were removed from the experiment and the size of the stomach (bloating) and the presence of adhesions with adjacent organs were evaluated macroscopically by the following criteria: erosions and hemographies, hyperemia, edema and mucosal fold disorders. For each group, the percentage of experimental animals was calculated according to these characteristics and the average value of their severity. The values of the ulcer index were calculated for each group. Research results and their discussion. The introduction of ethanol-prednisolone mixture causes erosive ulcerative lesions of the gastric mucosa in 100% of rats The introduction of cryoextract placenta significantly reduced the damaging effect of ulcerogenic mixture on the mucous membrane, advice on the performance of control rats. The severity of antiulcer activity of the studied cryoextract in the prophylactic mode of use is statistically significantly (p&lt;0.05) exceeds the similar effect of esomeprazole. Conclusions. Prophylactic five-day administration of cryopreserved placenta extract is accompanied by a statistically significant (p&lt;0.05) marked gastroprotective effect in a model of ethanol-prednisolone gastric lesions in rats.

Robert's Intragastric Alcohol-Induced Gastric Lesion Model as an Escalated General Peripheral and Central Syndrome, Counteracted by the Stable Gastric Pentadecapeptide BPC 157.

We redefined Robert’s prototypical cytoprotection model, namely the intragastric administration of 96% alcohol in order to generate a general peripheral and central syndrome similar to that which occurs when major central or peripheral veins are occluded in animal models. With this redefinition, we used Robert’s model to examine the cytoprotective effects of the stable gastric pentadecapeptide BPC 157. The intragastric administration of alcohol induced gastric lesions, intracranial (superior sagittal sinus) hypertension, severe brain swelling and lesions, portal and vena caval hypertension, aortal hypotension, severe thrombosis, inferior vena cava and superior mesenteric vein congestion, azygos vein failure (as a failed collateral pathway), electrocardiogram disturbances, and heart, lung, liver and kidney lesions. The use of BPC 157 therapy (10 µg/kg or 10 ng/kg given intraperitoneally 1 min after alcohol) counteracted these deficits rapidly. Specifically, BPC 157 reversed brain swelling and superior mesenteric vein and inferior vena caval congestion, and helped the azygos vein to recover, which improved the collateral blood flow pathway. Microscopically, BPC 157 counteracted brain (i.e., intracerebral hemorrhage with degenerative changes of cerebral and cerebellar neurons), heart (acute subendocardial infarct), lung (parenchymal hemorrhage), liver (congestion), kidney (congestion) and gastrointestinal (epithelium loss, hemorrhagic gastritis) lesions. In addition, this may have taken place along with the activation of specific molecular pathways. In conclusion, these findings clarify and extend the theory of cytoprotection, offer an approach to its practical application, and establish BPC 157 as a prospective cytoprotective treatment.

Comparison of the preventive effects of Murraya exotica and Murraya paniculata on alcohol-induced gastric lesions by pharmacodynamics and metabolomics

Ethnopharmacological relevanceMulti-source phenomenon is very common for traditional Chinese medicine (TCM). Both Murraya exotica L. (ME) and Murraya paniculata (L.) Jack (MP) are used as the source plants of Murrayae Folium et Cacumen (MFC), a traditional Chinese medicine recorded in Chinese Pharmacopoeia for promoting qi and relieving pain, mainly for the treatment of stomach pain, rheumatism and arthralgia. However, up to now, there has been no comparative study of these two plants on their efficacies and mechanisms, thus, further research is needed to evaluate their similarity and difference in order to judge the reasonability for their common usage.Aim of the study: This study aims to compare the effects and potential mechanisms of ME and MP, the two source plants of MFC on gastric lesions in rats by pharmacodynamics and metabolomics. Materials and methodsA rat model of gastric lesions induced by 70% aqueous ethanol and 150 mmol/L HCl was established and adopted to evaluate the gastric protective effects of ME and MP by analysis of the lesion index, histopathological changes (observed by H&E staining and TUNEL staining) and cytokine levels (IL-1β, IL-6, TNF-α, MTL, and GAS). The potential mechanisms were investigated by LC-MS metabolomic analysis of the rat plasma. ResultsME and MP showed the similar effects on improving the lesions of rat stomachs and reducing the cytokine levels related to inflammation and digestion of rats. The metabolomics results showed that the metabolism of rats with gastric lesions was abnormal mainly in lipid metabolism, energy metabolism, and amino acid metabolism. ME and MP demonstrated a similar metabolic modulation for gastric lesions by acting on the similar pathways and metabolites. Also, PLA2 pathway was proved as an important pathway for ME and MP modulation of glycerophospholipid metabolism in gastric lesions. ConclusionsOur results proved that it is feasible and reasonable to use both of ME and MP as the source plants of MFC, at least for the treatment of gastric lesions, due to their similar pharmacodynamics and metabolic modulation ability. Moreover, the combination of pharmacodynamics and metabolomics is an efficient means for multi-source TCM study.

Microencapsulation of green tea extract (Camellia sinensis var assamica) to increase the bioaccessibility of bioactive compounds and gastroprotective effects

Green tea has polyphenols and flavonols as its main bioactive constituents, nonetheless, these compounds present sensitivity to external factors. Microencapsulation is a technique that can be used to protect the main bioactive constituents of green tea. This research was carried out aiming to obtain scientific evidence on the in vitro simulated gastrointestinal digestion (SGD) of the green tea extract (Camellia sinensis var assamica) microencapsulated with cashew gum and maltodextrin and the gastroprotective action of these microcapsules in an experimental model of gastric lesion induced by ethanol in mice. The microencapsulation (GTM) process was able to increase the bioaccessible percentage of polyphenols and antioxidant activity of green tea after SGD in vitro, resulting in values equal to 28.2 and 24.2%, respectively. On the other hand, the bioaccessible percentage obseverd for green tea extract (GTE) was equal to 25.9 and 14% for the phenolic compounds and antioxidant activity, respectively. It was verified an action dose-way dependent related to the administration of GTE and GTM and their gastroprotective effects. The concentration of 10 mg/kg presented effective protection of the gastric mucosa, providing the maintenance of glutathione in the tissues after the alcoholic induced lesion and in the same concentration, the samples were able to avoid the lipidic peroxidation due to the reduction of malonaldehyde levels in the tissues. In general, GTM presented a great potential to contribute to the obtention of new products enriched with green tea, presenting also gastroprotective effect being beneficial to the consumer's health.

Cashew apple byproduct: Gastroprotective effects of standardized extract

Ethnopharmacological relevanceThe incidence of gastric mucosa lesions in the adult population has increased mainly due to the continued use of nonsteroidal anti-inflammatory drugs (NSAIDs). The cashew (Anacardium occidentale L.) is a tropical tree, cultivated in several countries, whose barks, leaves and pseudofruit (cashew apple) are popularly used in traditional medicine for the treatment of many diseases, including gastric ulcer. AimOur study evaluated the potential gastroprotective effect of the carotenoid and anacardic acids-enriched aqueous extract (CAE), prepared from cashew apple pomace, in the dose-repeated acetylsalicylic acid (ASA)-induced gastric lesions model in rats. Material and methodsAfter randomly distribution into five group (G1 – G5, n = 8 animals/group), male Wistar rats were daily treated with ASA solution (200 mg/kg, 5 ml/kg, G2 - G5) or potable water (Satellite group, G1) during 14 days. From 8th to 14th experimental day, rats in G3 - G5 groups were orally treated with CAE (50, 100 and 500 mg/kg, 5 ml/kg, respectively). Body weight was measured on 0, 7th and 14th day. On the 14th experimental day, all surviving animals were euthanized for macroscopic evaluation of the inner organs and stomach removal. After weighting, each stomach was properly prepared for biochemical analysis [myeloperoxidase activity (MPO), reduced glutathione analysis (GSH), IL-1β, CXCL2/MIP-2, TNF-α and IL-10 levels]. ResultsAt the most efficient dose (100 mg/kg, p.o.), CAE-treated animals showed a slight improvement in the macroscopic aspect of gastric mucosa associated with significant (p < 0.05) reduced levels of IL-1β, CXCL2/MIP-2, and MPO activity besides increased levels of GSH (partially), and IL-10 in stomach tissues. ConclusionsThe present study demonstrated that the carotenoid and anacardic acids-enriched extract obtained from cashew apple pomace is a promising raw material for the development of herbal medicine and/or functional food supplements for the adjuvant treatment of NSAIDs-induced gastric ulcers.

Sildenafil attenuates nonsteroidal anti-inflammatory-induced gastric ulceration in mice via antioxidant and antigenotoxic mechanisms.

Sildenafil (SIL) has potential as an interesting gastroprotective drug. However, the pathways of its protective effect still needs to be clarified, and its use as a potential gastroprotective agent validated. This study aims to evaluate the effects of SIL via modulation of oxidative stress in a NSAID-induced gastric lesion model. Male Swiss mice were divided into six groups: control (CON, water), nonsteroidal anti-inflammatory drug (NSAID, water), proton pump inhibitor (PPI, 30mg/kg of lansoprazole), SIL 5 (5mg/kg), SIL 25 (25mg/kg) and SIL 50 (50mg/kg). The animals were treated by gavage (a single dose) after 24hours of fasting, and gastric lesions were performed after 30minutes, with indomethacin (40mg/kg, by gavage). After 6h, the animals were killed and the stomach was removed to evaluate reactive oxygen species (ROS) production, oxidation of macromolecules, quantification of antioxidant enzymes, DNA fragmentation, apoptosis and macroscopic and histologic analysis of gastric lesions. SIL exerts a dose-dependent gastroprotective effect against NSAID-induced mucosal injury, also reducing cytoplasmic levels of ROS and consequent oxidative damage to macromolecules. In addition, SIL increases nitric oxide bioavailability, antioxidant enzymes and gastric cellular viability, as well as restoring important factors involved in gastroprotection. Our results demonstrate that different doses of SIL prevent indomethacin-induced gastric ulcer in mice via different, but complementary antioxidant, antigenotoxic and antiapoptotic mechanisms.

Gastroprotective and cicatrizing activity of the Ziziphus joazeiro Mart. leaf hydroalcoholic extract.

Ziziphus joazeiro Mart., popularly known as 'juazeiro', is a species used in popular medicine for the treatment of bronchitis, gastric ulcers, skin wounds, and in the manufacture of cosmetic and food products. The objective of this study is to evaluate the gastroprotective and cicatrizing activity of the Z. joazeiro Mart. leaf hydroalcoholic extract (EHFZJ). The acute pre-clinical toxicity was determined by the single administration of the EHFZJ (2000 mg/kg/p.o.) and by assessing clinical signs of toxicity, according to established criteria by Malone, or mortality. Gastroprotective activity was identified through classical models of acute gastric lesions induced by indomethacin, absolute and acidified ethanol (100, 200 and 400 mg/kg/per os) and the physical barrier mechanism (400 mg/kg/per os or intraperitoneally). The cicatrizing activity of the EHFZJ was investigated by measuring the speed of wound closure and the percentage of contraction. The acute pre-clinical toxicity of EHFZJ showed no signs of toxicity and mortality. The EHFZJ demonstrated a gastroprotective effect at the 400 mg/kg dose in the classical models of acute gastric injury induced by indomethacin, absolute and acidified ethanol. The EHFZJ administration (orally) demonstrated significant inhibition, suggesting a possible physical barrier mechanism exists. The EHFZJ showed no significant differences in terms of percentage of contraction or the speed of wound closure during the observation times (0, 3, 7, 11 and 14 days). The results obtained in this study provide evidence of a potential gastroprotective activity for the Ziziphus joazeiro Mart. Leaf hydroalcoholic extract.

Evaluation of Antiulcer Activity of Ethanol Extract of Leaves of Lactuca sativa

In this modern era, gastrointestinal disorders are the universal problem. Peptic ulcer is one of the major diseases affecting the human population. It develops due to the imbalance between aggressive factors like acid, pepsin, H. pylori and bile salts and defensive factors like mucous, bicarbonate, blood flow, epithelial cell restoration and prostaglandins. The anti-ulcer activity of Ethanol extract of leaves of Lactuca sativa (EELS) was estimated using the experimental models of acute gastric lesions induced by ethanol, pylorus ligation and cold restraint stress in Wistar albino rats. Animals pre-treated with doses of 250 mg/kg, 500 mg/kg of EELS were statistically analyzed and compared to the standard and control group with the parameters like volume of gastric secretion, total acidity and ulcer index. The results suggested that EELS significantly decreased volume of gastric acid secretion, total acidity and ulcer index in comparison with standard drug Omeprazole. EELS shown significant reduction in lesion index, total affected area and percentage of lesion in comparison with control group in Ethanol induced ulcer in experimental models. The gastric mucosal protective effect of EELS is brought by inhibiting the gastric secretion, which shows it may act like a proton pump inhibitor. Thus the present study indicates that EELS has anti-ulcerogenic potency in Ethanol induced, pylorus ligation and cold restraint stress induced ulcers in rats.&#x0D; Keywords: Antiulcer, ulcer index, cold stress, peptic ulcer, pylorus ligation

Gastroprotective activity of punicalagin and Lafoensia pacari in mice

Lafoensia pacari A. St.-Hil., Lythraceae, is used in Brazilian folk medicine to treat ulcer and gastritis; thus, it is important to conduct research so as to better understand its medicinal properties. The aim of this study was to assess the antisecretory and antiulcerogenic activities of lyophilized aqueous fraction and punicalagin isolated from leaves of L. pacari. Antisecretory gastric acid activity and antiulcerogenic activity were investigated by pyloric ligation-induced and indomethacin-induced gastric lesion models, respectively. Results show that the lyophilized aqueous fraction of L. pacari and punicalagin reduced the volume of gastric secretion, free acidity, and total acidity in mice 4 h after pyloric ligation, as well as the rate of gastric damage following the indomethacin administration model. Reduction percentages varied according to the dose of each treatment and showed statistical difference. This finding indicates that the lyophilized aqueous fraction of L. pacari and punicalagin exert an antiulcerogenic effect due to their acid antisecretory activity.