Gastro protective natural polymer aided triple drug therapy to eradicate Helicobacter pylori.

The core intent of the existing effort was to explore a triple therapy to eradicate Helicobacter pylori. A hard gelatin capsule filled with metronidazole (MNZ) floating microspheres aided with Plantago ovata seed mucilage (POSM) and Clarithromycin (CMN) floating microspheres aided with Abelmoschus esculentus fruit mucilage (AEFM). These mucilages were adopted as they have gastro-protective actions. These microspheres were designed by a central composite design. The influence of polymers used was checked towards the drug entrapment efficacy and floating time was tallied as a response. The capsule also contains Pantoprazole sodium (PZS) enteric-coated mini-tablets. These mini-tablets were checked for the coating thickness as a response (Design Expert). The microspheres and the mini-tablets were gauged for tests and a positive response was reported. The study summarizes that microspheres of MNZ & CMN and PZS enteric-coated mini-tablets can be used to eradicate H. pylori effectively. POSM and AEFM can aid MNZ and CMN microspheres formulations and have ulcer-curing and gastric-protective abilities.

Gastroprotective role of a flavonoid-rich subfraction from Fridericia chica (Bonpl.) L. G. Lohmann: a medicinal plant used in the Amazon region.

Fridericia chica is an Amazonian plant used to treat stomach disorders. However, the pharmacological activity of flavonoids in the extract has yet to be investigated. Therefore, we considered that a flavonoid-rich F. chica subfraction (FRS) has gastroprotective functions. For this, before the induction of gastric ulcers with ethanol or piroxicam, the rats received vehicle (water), omeprazole (30 mg/kg), or FRS (30 mg/kg), and the ulcer area was measured macro and microscopically, and the antisecretory action was investigated in pylorus-ligated rats. In addition, the roles of nitric oxide (NO) and nonprotein sulfhydryl compounds (NP-SH) in the gastroprotective effects of FRS were studied. FRS reduced ethanol- and piroxicam-induced ulcerations by 81% and 77%, respectively, as confirmed histologically. Antioxidant effects were observed for FRS through the maintenance of GSH and LPO levels, and the SOD and CAT activity similar to those found in the nonulcerated group. Moreover, FRS avoided the increase in MPO activity and TNF, IL-6, IL-4 and IL-10 levels. Moreover, mucin staining increased in ulcerated rats receiving FRS, and the pharmacological mechanism gastroprotective seems to involve the NO and NP-SH in addition to antisecretory actions. The chemical study by mass spectrometry confirmed the presence of flavonoids in FRS, and molecular docking studies have shown that these compounds interact with cyclooxygenase-1 and NO synthase. Furthermore, there was no indication that FRS had cytotoxic effects. Our results support the popular use of F. chica, and we conclude that the gastroprotection effect promoted by FRS can be attributed to the combined effect of the flavonoids.

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 472.39 µg/mL in the tests ABTS and DPPH. In the nociceptive test, EOEf showed a 72.05% reduction in nociception at a dose of 100 mg/kg. In evaluating the anti-inflammatory effect, the essential oil inhibited paw edema by 95.50% and 97.69% at doses of 50 and 100 mg/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.

Rosuvastatin repurposing for prophylaxis against ethanol-induced acute gastric ulceration in rats: a biochemical, histological, and ultrastructural perspective.

Ethanol (EtOH) consumption is frequently associated with acute and chronic gastrointestinal disorders. Rosuvastatin (RSV), a third-generation statin, has demonstrated certain biological functions beyond its lipid-lowering properties. This study is designed to explore the gastroprotective impact of RSV in a rat model of EtOH-induced gastric ulceration in a dose-dependent manner through the evaluation of oxidant/antioxidant biomarkers, inflammatory myeloperoxidase (MPO) enzyme activity, and prostaglandin E2 (PGE2) levels in gastric tissues, along with histopathological examination of the gastric tissues. Therefore, 40 adult male rats were randomly divided into five equal groups as control, EtOH (gastric ulcer), RSV-low dose plus EtOH and RSV-high dose plus EtOH. The EtOH rat model of gastric ulceration was achieved by intragastric administration of a single dose of EtOH. Seven days before EtOH administration, rats were orally administered either omeprazole (20 mg/kg/day) or RSV (10 mg/kg/day or 20 mg/kg/day). RSV administration enhanced the antioxidant glutathione reduced, countered oxidative malondialdehyde, augmented cytoprotective PGE2, suppressed inflammatory MPO enzyme activity in gastric tissues, decreased ulcer index scoring, increased the percentage of ulcer inhibition, and reversed the associated histological and ultrastructural abnormalities, additionally, RSV treatment resulted in weak positive nuclear staining for the inflammatory nuclear factor kappa B in a dose-dependent manner. It is concluded that RSV demonstrates gastroprotective potential, attributable at least in part, to its antioxidant and anti-inflammatory properties, as well as its ability to promote ulcer protection through the maintenance of mucosal content and PGE2 levels. Thus, RSV therapy emerges as a safe option for patients with gastric ulcers.

Pharmacodynamics Between a Dual Delayed-Release Formulation of Low-Dose Esomeprazole and Famotidine in Healthy Korean Subjects.

PURPOSE: Gastritis, one of the most common clinically diagnosed conditions, is defined as the infiltration of inflammatory cells into the gastric mucosa. Drugs for gastritis include histamine-2 receptor antagonists and proton pump inhibitors (PPIs), which reduce acidity in the stomach, and antacids, which neutralize acid. Esomeprazole is a PPI for gastroesophageal reflux disease and gastric and duodenal ulcers that has been shown to be safe and effective at a 10 mg dose. Dual-release drugs have not yet been approved for the treatment of gastritis domestically or internationally. In this study, a dual delayed-release (DR) esomeprazole (10 mg), was compared to famotidine (20 mg) to determine its effectiveness in the treatment of gastritis. METHODS: This study was a randomized, open-label, multiple-dose, 2-treatment, 2-period, 2-sequence crossover study with a 7-day washout between periods. In each period, the subjects were administered one dose of esomeprazole (10 mg) or famotidine (20 mg) for 7 days at each period. The 24-hour gastric pH was recorded after single and multiple doses. The percentage of time (duration%) that the pH was maintained above 4 in the 24 hours after 7 days of repeated dosing was evaluated. FINDINGS: The mean percentages of time that the gastric pH was above 4 after multiple doses over 7 days of a dual DR esomeprazole (10 mg) and famotidine (20 mg) was 47.31% ± 14.85% and 23.88% ± 10.73%. IMPLICATIONS: Multiple doses of a dual DR esomeprazole (10 mg) showed effective gastric acid secretion suppression compared to famotidine with comparable safety and tolerability. These results provide evidence supporting the clinical use of a dual DR esomeprazole (10 mg) to treat gastritis. CLINICALTRIALS: gov identifier: NCT04967014.

Targeting TRPV1 signaling: Galangin improves ethanol-induced gastric mucosal injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Galangin, a bioactive compound extracted from Alpinia officinarum Hance (Zingiberaceae), a plant with significant ethnopharmacological importance, has been used for thousands of years as a spice, condiment, and medicinal agent for various conditions, including gastrointestinal disorders. Although there is evidence suggesting its potential to improve gastric ulcers, the molecular mechanisms underlying its anti-ulcer properties are not fully understood. OBJECTIVE: of the Study: This study aimed to investigate the effects of galangin on ethanol-induced acute gastric mucosal injury (AGMI) in mice and elucidate its molecular mechanisms. MATERIALS AND METHODS: Sixty BALB/c mice were randomly assigned into two main groups: a normal control group (n = 10) and an ethanol-induced group (n = 50). After establishing the AGMI model in mice using a combination of 40% ethanol and anhydrous ethanol, the ethanol-induced group was further subdivided into five subgroups (n = 10): an omeprazole control group (20 mg/kg), an untreated ethanol group, and three treatment groups receiving high-dose (50 mg/kg) or low-dose (25 mg/kg) galangin or capsazepine (CPZ, 2 mg/kg). The protective effects of galangin were evaluated through mucosal injury indices, hematoxylin and eosin staining, and quantification of inflammatory markers (IL-1ß, IL-6, IL-8, and TNF-α). Oxidative stress levels and matrix metalloproteinase activity were measured using specific assay kits. Molecular docking was conducted to assess the binding affinity of galangin to key proteins within the transient receptor potential vanilloid 1 (TRPV1) pathway. Real-time fluorescence quantitative PCR (qPCR) was used to determine mRNA expression levels of TRPV1, calmodulin (CaM), substance P (SP), and CGRP in gastric tissues. Protein expression levels of TRPV1, nerve growth factor (NGF), tropomyosin receptor kinase A (TRKA), transforming growth factor beta (TGF-ß), cyclooxygenase-2 (COX-2), and nuclear factor kappa B (NF-κB) were assessed through Western blot analysis. In cellular experiments, Culture of Human Gastric Epithelial Cells (GES-1) were treated with various concentrations of galangin after 7% ethanol induction. Cell proliferation, apoptosis, and migration were evaluated using Hoechst 33258 staining and transwell migration assays. TRPV1 protein expression was detected using immunofluorescence, and the expression levels of Bcl-2, BCL2-Associated X (BAX), and Caspase-3 were quantified by qPCR. Additionally, specific probe kits were used to measure intracellular calcium ions (Ca2+) and mitochondrial membrane potential. RESULTS: The findings indicate that galangin significantly improved mucosal pathology by reducing ulcer indices and inflammatory levels, while enhancing superoxide dismutase (SOD) activity and decreasing malondialdehyde (MDA) concentration. Galangin also reduced matrix metalloproteinase-2 (MMP-2), m metalloproteinase-9 (MMP-9) levels, promoting mucosal repair. At the cellular level, galangin decreased intracellular calcium ion concentration and mitigated the decline in mitochondrial membrane potential, enhance the restoration of mucosal cells, increased migration and proliferation, and reduced apoptosis. Molecularly, galangin demonstrated favorable binding to TRPV1, NGF, TRKA, TGF-ß, COX-2, and NF-κB, and reversed the elevated expression of these proteins. Additionally, galangin downregulated the mRNA expression of TRPV1, CaM, SP, CGRP, BAX, and Caspase-3 in gastric tissues/cells, while upregulating Bcl-2 mRNA expression. CONCLUSION: Galangin mitigates AGMI by inhibiting the overactivation of the TRPV1 pathway, thereby blocking aberrant signal transduction. This study suggests that galangin has therapeutic potential against ethanol-induced AGMI and may be a viable alternative for the treatment of alcohol-induced gastric mucosal injuries.

In vivo anti-gastric ulcer activity of 7-O-methyl aromadendrin and sakuranetin via mitigating inflammatory and oxidative stress trails.

ETHNOPHARMACOLOGICAL RELEVANCE: Eucalyptus genus has been used for a very long time in conventional treatment as an anti-ulcer remedy. AIM OF THE STUDY: The study aimed to explore the gastroprotective potential of 7-O-methyl aromadendrin (7-OMA), and sakuranetin (SKN) in comparison with omeprazole. The study tackled the contribution of their anti-inflammatory, antioxidant, and antiapoptotic capabilities to their anti-gastric ulcer effects. MATERIALS AND METHODS: An ethanol-induced gastric ulcer model in rats was adopted and the consequences were confirmed by a molecular docking study. RESULTS: The oral pretreatment of rats 1 h before ethanol using omeprazole (20 mg/kg) or 7-OMA (20 or 40 mg/kg) or SKN (20 or 40 mg/kg) exhibited gastroprotective and anti-inflammatory properties to different extents. These amendments witnessed as restorations in the stomach histological architecture in H and E-stained sections, mucus content in periodic acid-Schiff (PAS) stained sections with increased cellular proliferation, as demonstrated by increased immunohistochemical staining of PCNA, and increments in stomach COX-1 activity and eNOS. The highest dose of SKN showed the best corrections to reach 4.8, 1.8, and 2.1 folds increase in PAS, COX-1 and eNOS, respectively as compared to the untreated ethanol-induced gastric ulcer group; effects that were comparable to that of omeprazole. Moreover, reductions in COX-2 activity, and the protein expression of NF-κB, IL-6, TNF-α and NOx, in addition to the gene expression of inducible iNOS were also noted. Moreover, the antioxidant and antiapoptotic capabilities of omeprazole, 7-OMA, and SKN were perceived. SKN (40 mg/kg) succeeded to show the unsurpassed results to reach 293.6%, 237.1%, 274.7%, 248.2%, and 175.4% in total and reduced GSH, catalase, SOD, and Bcl2, respectively, as well as 50.0%, 46.8%, and 52.1 % in oxidized GSSG, TBARS and caspase-3, respectively. The gastroprotective potential of the tested compounds can be assigned to their anti-inflammatory, antioxidant and antiapoptotic properties.7-OMA and SKN were studied using molecular docking into the binding sites of the most significant inflammatory targets, including COX-2, TNF-α, iNOS, and NF-κB. Pharmacokinetic and physicochemical parameters in silico were appropriate. CONCLUSION: The prophylactic use of 7-OMA and SKN could be considered as an add-on to recurrent gastric ulcers and might influence its therapeutic approaches.

Evaluation of Synergistic Activity of Ethanolic Leaf Extracts of Tephrosia Purpurea and Bacopa Monnieri in Ulcer Induced Rats.

OBJECTIVE: To evaluate synergistic antiulcer activity of ethanolic extracts of Tephrosia purpurea and Bacopa monnieri in ulcer induced rats. METHODS: Ethanolic leaf extracts of both the plants were administered individually and in combination at a dose of 200mg/kg to ulcer induced male albino rats. Omeprazole 10mg/kg was used as standard. Pylorus ligation method, ethanol and indomethacin induced gastric ulcer models were the different gastric ulcer models selected for the induction of ulcer in rats. Ulcer index, ulcer score, total acidity, pH, percentage protection, volume of gastric juice were the parameters evaluated and compared in different groups in all the models. RESULTS: Decrease in the ulcer score, ulcer index, total acidity was observed and percentage protection was significant(*p<0.05 and p<0.01) with the combination extract compared to group received individual plant extracts. CONCLUSION: Our results suggested that combination of two medicinal plants showed synergistic anti ulcer activity and decreased the formation of ulcer lesions in rats.

The Gastroprotective Effects of Anisomeles indica against Ethanol-Induced Gastric Ulcer through the Induction of IκB-α and the Inhibition of NF-κB Expression.

Anisomeles indica (L.) Kuntze is a traditional herb with multiple medicinal properties and with potential for preventing or treating various diseases. Acteoside, one of the active ingredients in A. indica, is prepared into commercially available products of A. indica HP813 powder. In this study, the gastroprotective effects of A. indica HP813 powder were evaluated. Wistar rats were treated with A. indica HP813 powder at doses of 0, 207.5, 415, and 830 mg/kg body weight for 28 days. Then, gastric ulcers were induced by the oral administration of 70% ethanol (10 mL/kg body weight) on day 28. The rats were sacrificed at the end of the trial, and stomach tissues were collected. These stomach tissues were then used for macroscopic, microscopic, and immunohistochemical analyses. The results indicated that the area of gastric ulcer was 48.61%, 35.30%, and 27.16% in the ethanol-induced group, 415 mg/kg A. indica HP813 powder group, and 830 mg/kg A. indica HP813 powder group, respectively. In addition, the lesion scores were 2.9, 2.4, and 2.3 in the ethanol-induced group, 415 mg/kg A. indica HP813 powder group, and 830 mg/kg A. indica HP813 powder group, respectively. The immunochemical staining of the gastric tissue revealed that A. indica HP813 powder reduced the expressions of TNF-α and NF-κB proteins in the gastric tissue, which had been induced by ethanol. Finally, A. indica HP813 powder protected the gastric ulcer from ethanol damage through IκB-α induction. The present results demonstrated that A. indica HP813 powder has protective effects against ethanol-induced gastric ulcer.

Concomitant Effects of Metformin and Vitamin C on Indomethacin-Induced Gastric Ulcer in Rats: Biochemical and Histopathological Approach.

INTRODUCTION: Gastric ulcer is one of the most common and serious conditions in the gastrointestinal tract. One of the main causes of gastric ulcers is using of non-steroidal anti-inflammatory drugs (NSAIDs) which have limited their use in clinical practice. Several studies have revealed that metformin and Vitamin C (Vit C) exhibit protective effects against gastric mucosal damage in different animal models. However, no studies indicate their combination's effect on gastric ulcer models. Therefore, this study aims to investigate the protective effects of metformin and Vit C combination on indomethacin-induced gastric ulcers. MATERIAL AND METHODS: In total, thirty rats were divided into six groups, including the control group, rats received indomethacin (50 mg/kg, i.p.), rats received indomethacin and pretreated with ranitidine (100 mg/kg), metformin (100 mg/kg, i.p.), Vit C (100 mg/kg), or metformin combined with Vit C. Four hours after indomethacin administration, rats were euthanized, and gastric tissues were removed for macroscopic, histopathologic, and biochemical examinations. RESULTS: All therapeutics used in this study were found to alleviate gastric mucosal injury caused by indomethacin, as observed in histopathologic and macroscopic evaluations. Both Vit C and metformin were observed to significantly decrease lipid peroxidation and enhance the activity of anti-oxidative enzymes, SOD, GPx, and catalase. However, a more significant effectiveness was observed in catalase and GPx activities when Vit C was co-administered with metformin. CONCLUSIONS: In conclusion, the present study revealed that metformin and Vit C combination therapy could potentially treat gastric ulcers associated with indomethacin.

Wood calamint ameliorates ethanol-induced stomach injury in rats by augmentation of hsp/bax and inflammatory mechanisms.

Clinopodium menthifolium (wood calamint) is a folkloric medicinal plant ingested as a treatment for many human disorders including gastric disorders. Our study evaluates the anti-ulcer potentials of Clinopodium menthifolium ethanol extracts (CMEE) in induced gastric ulcers in rats. Thirty Dawley male rats were divided into 5 groups: normal and ulcer controls, treated orally with Tween 20%; reference rats treated with Omeprazole 20 mg/kg, and the remaining two groups received 250 and 500 mg/kg CMEE for 2 weeks. After that, food was taken away for 24 h, and then, rats received ethanol-induced gastric ulceration (except normal control), 80% (1 ml/rat). After anesthetization and sacrificing, the ulcer index, mucus content, and other ulcer measurements were obtained from dissected rat stomachs. Stomach tissues were also analyzed by different histology procedures and homogenized stomach tissues were assessed for their antioxidant contents. The toxicity trial showed the absence of any toxic signs in rats supplemented with 2 and 5 g/kg of CMEE. The gastroprotective results showed a significantly lower ulcer index and higher gastric mucin content in CMEE-ingested rats compared to ulcer controls. Furthermore, CMEE treatments significantly increased the intensity of periodic acid Schiff stained (PAS), HSP 70 protein, and down-regulation of Bax protein expression in the stomach epithelium. Rats supplemented with 500 mg/kg revealed noticeable changes in their serum inflammatory cytokines along with positive regulations of antioxidant enzymes. The outcomes provide a scientific backup behind the gastroprotective potential effect of CMEE that could serve as a natural resource against peptic ulcers.

Pharmacological insight of rutin as a potential candidate against peptic ulcer.

Peptic ulcer is a sore on the stomach lining that results from the erosion of the gastrointestinal tract mucosa due to various influencing factors. Of these, Helicobacter pylori infection and non-steroidal anti-inflammatory drugs (NSAIDs) stand out as the most prominent causes. This condition poses a significant global health concern due to its widespread impact on individuals worldwide. While various treatment strategies have been employed, including proton pump inhibitors and histamine-2 receptor antagonists, these have notable side effects and limitations. Thus, there is a pressing need for new treatments to address this global health issue. Rutin, a natural flavonoid, exhibits a range of biological activities, including anti-inflammatory, anticancer, and antioxidant properties. This review explores the potential anti-ulcer effect of rutin in experimental models and how rutin can be a better alternative for treating peptic ulcers. We used published literature from different online databases such as PubMed, Google Scholar, and Scopus. This work highlights the abundance of rutin in various natural sources and its potential as a promising option for peptic ulcer treatment. Notably, the anti-inflammatory properties of rutin, which involve inhibiting inflammatory mediators and the COX-2 enzyme, are emphasized. While acknowledging the potential of rutin, it is important to underscore the necessity for further research to fully delineate its therapeutic potential and clinical applicability in managing peptic ulcers and ultimately improving patient outcomes. This review on the anti-ulcer potential of rutin opened a new door for further study in the field of alternative medicine in peptic ulcer management.

The gastroprotective effect of Yucca filamentosa standardized crude leaves extract versus its nano-cubosomal formulation in ethanol-induced gastric injury.

Yucca filamentosa (YF) is widely used in folk medicine for its anti-inflammatory effects. Our study aimed to evaluate the chemical profile of YF extracts. Additionally, the gastroprotective efficacy of its crude leaf extract and nano-cubosomal formulation was assessed in a rat model of ethanol-induced gastric injury by altering the HMGB-1/RAGE/TLR4/NF-κB pathway. The phytochemical composition of YF was investigated using FTIR spectroscopy and LC-MS/MS techniques. Standardization was further accomplished using HPLC. Rats were treated orally with yucca crude extract or its nano-cubosomal formulation at doses of 25, 50, and 100 mg/kg. Famotidine (50 mg/kg, IP) was used as a reference drug. After 1 h, rats were administered ethanol (1 ml, 95 %, orally). One hour later, the rats were sacrificed, and the serum was separated to determine TNF-α and IL-6 levels. Stomachs were excised for the calculation of the ulcer index and histopathological examinations. Stomach tissue homogenate was used to determine MDA and catalase levels. Additionally, the expression levels of HMGB-1/RAGE/TLR4/NF-κB were assessed. Phytochemical analysis confirmed the predominance of steroidal saponins, sucrose, organic and phenolic acids, and kaempferol. The nano-cubosomal formulation demonstrated enhanced gastroprotective, anti-oxidant, and anti-inflammatory efficacy compared to the crude extract at all tested doses. The most prominent effect was observed in rats pretreated with the YF nano-cubosomal formulation at a dose of 100 mg/kg, which was similar to normal control and famotidine-treated rats. Our results highlighted the enhanced gastroprotective impact of the yucca nano-cubosomal formulation in a dose-dependent manner. This suggests its potential use in preventing peptic ulcer recurrence.

Echinophora tournefortii Jaub. & Spach: Evaluation of the effect on indomethacin-induced gastric ulser in rats and phytochemical analyses by LC-HRMS.

E. tournefortii has wound healing properties in folk medicine and 5% infusions are used for stomach ulcers. It is also used in colds, abdominal pain, digestive problems, as an appetite enhancer and antispasmodic. For this purpose, in the study biochemical and histopathological evaluation of the ulcer protective effect of the extract obtained from the E. tournefortii in the indomethacin-induced gastric ulcer model in rats was aimed to develop new strategies in the treatment of ulcers. The phytochemical profile of the plant was elucidated for the first time by LC-HRMS in this study. The results indicate that, in terms of TNF-α, IL-1ß, IL-8, IL-6, PGE2, NF-κB, VEGF, NO, COX-1 and COX-2 biochemical parameters, E. tournefortii protects the gastric mucosa to the inflammation, and also modulates the PGE2 pathway, and has a similar effect or even a more positive effect than the reference substance lansoprazole. According to LC-HRMS analysis results, chlorogenic acid, genistein and quinic acid were the main constituents of E. tournefortii extract with 1397.081, 1014.177 and 992.527µg/g extract, respectively. Considering the anti-inflammatory and antioxidant effects of these phenolic components, it is thought that the major components are responsible for the anti-ulcer activity of the E. tournefortii extract.

Parthenolide alleviates indomethacin-induced gastric ulcer in rats via antioxidant, anti-inflammatory, and antiapoptotic activities.

Parthenolide (PTL) is a sesquiterpene lactone that occurs naturally. It demonstrates a variety of beneficial effects, such as antioxidant, anti-inflammatory, and antiapoptotic properties. The study investigated the potential protective impact of PTL on indomethacin (INDO) induced stomach ulcers in rats. The rats were classified into 5 distinct categories. Group 1 served as the "control" group. Rats in the second group received a single oral dosage of INDO (50 mg kg-1). Rats in Groups three and four received 20 and 40 mg kg-1 oral PTL 1 h before INDO. Omeprazole (30 mg kg-1) was given orally to Group 5 rats 1 h before INDO. Pretreatment with PTL increased stomach pH and decreased gastric volume as well as reduced the morphological and histological changes induced by INDO. Analysis of probable pathways showed that pre-treatment with PTL successfully reduced oxidative, inflammatory, and apoptotic consequences caused by INDO. The ingestion of PTL leads to a notable increase in the levels of glutathione reduced (GSH) and the activities of superoxide dismutase (SOD) and catalase (CAT). Furthermore, PTL decreased the concentration of malondialdehyde (MDA). In contrast, it was shown that PTL increased both cyclooxygenase-1 (COX-1) and prostaglandin E2 (PGE2). PTL shows a significant decrease in the expression of interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), inducible nitric oxide synthase (iNOS), and nuclear factor kappa B (NF-κB). PTL therapy resulted in a decrease in Bcl-2-associated X protein (Bax) levels and an increase in B-cell lymphoma 2 (Bcl2) levels. In conclusion, PTL offers gastroprotection by its antioxidant, anti-inflammatory, and anti-apoptotic qualities.

Investigating the pharmacological potential of phytol on experimental models of gastric ulcer in rats.

Phytol is a diterpene constituent of many essential oils, belonging to the group of unsaturated acyclic alcohols. Although phytol possesses antimycobacterial and anti-inflammatory effects, no reports of a gastrointestinal action are available from the literature. Due to the well-known shortcomings of classical anti-ulcer drugs (e.g. side effects or relapses), natural products may offer an attractive alternative. In this study, a potential gastroprotective activity of phytol was evaluated using acute and chronic ulcer models in rats. Phytol 12.5, 25 and 50 mg/kg, administered orally 1 h prior to induction of gastric lesions by absolute ethanol, inhibited the lesion area by 96, 90 and 95%, respectively. When lesions were induced by ischemia and reperfusion, phytol 12.5 and 25 mg/kg per os decreased the lesion areas by 89 and 46%, respectively. In the third acute ulcer model (lesions induced by ibuprofen), phytol 12.5 mg/kg reduced the lesion area by 55%. Phytol restored the decreased level of reduced glutathione, the increased levels of myeloperoxidase and malondialdehyde and the decreased levels of catalase and superoxide dismutase in rats with gastric ulcer induced by ethanol to levels obtained in vehicle group. Finally, in a chronic model in which gastric ulcer was induced by acetic acid directly instilled into the stomach, phytol administered orally over a time period of 7 days at 12.5, 25, 50 and 100 mg/kg reduced lesion areas by 84, 81, 83 and 68%. Our data suggest a gastroprotective and cicatrizing effect of phytol, possibly associated with its antioxidant effect.

Anti-inflammatory, anti-oxidant and anti-ulcer activities of aqueous lyophilizate of Markhamia lutea (Bignoniaceae).

OBJECTIVES: This work was carried out with a view to determining the antioxidant, anti-inflammatory and anti-ulcer properties of the aqueous lyophilized extract of Markhamia lutea. METHODS: In vitro proteinases inhibition, albumin denaturation, hemolysis of red blood cells by heat, inhibition of the proton pump H+/K+ATPase, FRAP (Ferric reducing antioxidant power) and DPPH (1,1-diphenyl-2-picrylhydrazyl) assays were performed. In vivo, cold water immersion-induced ulceration and methylene blue-induced ulceration was used to determine the anti-ulcer properties of the lyophilizate (100, 200 and 300 mg/kg). RESULTS: In vitro, the lyophilizate (400 µg/mL) significantly inhibited protein denaturation (66.65 %), hemolysis of red blood cells (56.54 %), proteinase activity (69.22 %); then the IC50 was 26.31 µg/mL on proton pump activity. It has also developed a strong ferric reducing antioxidant power (EC50=52.96 mmol FeSO4/g) as well as free radicals scavenging activity (EC50=22.38 µg/mL). In vivo, the aqueous lyophilizate (200 and 300 mg/kg) protected the gastric mucosa (70.68 and 79.00 % protection respectively) and reduced (p<0.05) acetylcholine, calcium and corticosterone concentrations. A decrease in malondialdehyde level, an increased glutathione level and an increased in catalase and SOD activities were recorded. In the methylene blue test, it significantly increased gastric fluid pH, while reducing gastric volume and improving hematological parameters in ulcer animals. In addition, the histological sections show that the aqueous lyophilizate of M. lutea protected the gastric mucosa from the deleterious effects of stress. CONCLUSIONS: The aqueous lyophilizate of M. lutea has anti-ulcer properties thanks to its anti-inflammatory, antioxidant and anti-secretory properties.

Aibika Flower Flavonoid Extract Exhibits Antiulcer Activity in a Murine Model of Ethanol-Induced Acute Gastric Injury.

Aibika (Abelmoschus manihot (L.) Medic) is a garden vegetable whose flower has been shown to have various bioactivities. This study investigated the protective effect of aibika flower flavonoid extract (AFF) on ethanol-induced gastric injury in mice. The experimental results showed that pre-feeding 125 and 250 mg AFF/kg BW for 1 week significantly reduced the gastric injury area in the negative control group from 19.2% to 6.7% and 0.6%, respectively. The results of the pathological sections staining also showed that AFF had a protective ability against alcohol-induced injury of gastric tissue and liver tissue. When the mice were exposed to high concentrations of ethanol, AFF pretreatment significantly upregulated the expression of antioxidant enzymes. The pretreatment also promoted the production of the intracellular antioxidant, reduced glutathione, in both gastric tissue and serum. On the contrary, AFF delayed the lipid peroxidation process, which, in turn, reduced the damage to the gastric mucosa. When acute inflammation was induced by ethanol stimulation, AFF significantly downregulated the proinflammatory cytokines and mediators such as TNF-α, IL-1ß, IL-6, NF-κB, COX-2, and iNOS. Furthermore, AFF pretreatment greatly promoted the production of healing factors, such as matrix metalloproteinase (MMP)-2, MMP-7, and MMP-9, in the gastric tissue. In addition, AFF significantly reduced gastric cell apoptosis induced by ethanol stimulation. These results demonstrate that AFF has a good protective effect on alcohol-induced gastric ulcer and has the potential to be used in gastrointestinal health care.

Gastroprotective effects of polysaccharides from purple sweet potato (Ipomoea batatas (L.) Lam) on an ethanol-induced gastric ulcer via regulating immunity and activating the PI3K/Akt/Rheb/mTOR pathway.

The study aimed to investigate the alleviation of an ethanol-induced gastric ulcer in mice by apolysaccharide (PSP) from purple sweet potato (Ipomoea batatas (L.) Lam) and explore the mechanism. The anti-ulcer activity was determined by histopathological evaluation, total gastric acidity, pepsin activity, gastric ulcer index and gastric ulcer inhibition rate. The expression levels of inflammatory factors were detected using ELISA. A special protein meter was used to detect the content of immunoglobulin lgM, immunoglobulin lgG, and complements C3 and C4 in the serum of mice. The expression of CD4+/CD8+ lymphocyte subsets of mice was detected using flow cytometry. Western blot analysis was used to examine the effect of PSP on the PI3K/Akt/Rheb/mTOR pathway. The results showed that PSP could effectively reduce the total gastric acidity, pepsin activity, and the index and inhibition rate of gastric ulcers. At the same time, PSP could significantly increase the levels of immunoglobulins (lgG and lgM) and complements (C3 and C4). It could also increase the activity of peritoneal macrophages in mice and the expression of CD4+/CD8+ in the spleen. ELISA analysis showed that the contents of TNF-α, IL-1ß and IL-6 were significantly decreased and the content of IL-10 was significantly increased in the PSP group. The western blot analysis showed that PSP could upregulate the relative protein expressions of MUC5AC, PI3K, p-Akt, Rheb and mTOR. These results indicate that PSP can activate the PI3K/Akt/Rheb/mTOR signaling pathway to improve the immunity of mice and maintain the balance of the immune system, thereby protecting the gastric mucosa and improving stress gastric ulcers.

Evaluation of Gastroprotective Activity of the Methanolic Extract of Justicia pectoralis Jacq. (Acanthaceae).

INTRODUCTION: Justicia pectoralis Jacq. is traditionally applied in folk medicine in Brazil and in several Latin American countries. The leaves are used in tea form, especially in the treatment of respiratory disorders, acting as an expectorant. It also has activity in gastrointestinal disorders, and it is anti-inflammatory, antioxidant, sedative, and estrogenic, among others. AIMS: To investigate the gastroprotective activity of the methanol extract of the leaves of Justicia pectoralis Jacq. (MEJP) in different experimental models of gastric ulcers. MATERIALS AND METHODS: The adult leaves of Justicia pectoralis Jacq. were collected and cultivated in beds, with an approximate spacing of 40 × 40 cm, organic fertilization, irrigation with potable water and without shelter from light. The MEJP was prepared from the dried and pulverized leaves and concentrated under reduced pressure in a rotary evaporator. For the experimental model of gastric ulcer, Swiss male albino mice were used. The inputs used in the experiment were MEJP at three different concentrations (250, 500 and 1000 mg/kg p.o.), cimetidine (50 mg/kg p.o.), indomethacin (50 mg/kg s.c.) and vehicle (10 mL/kg p.o.). RESULTS: MEJP (250, 500 and 1000 mg/kg p.o.) demonstrated gastroprotective activity, with levels of protection of 45.65%, 44.80% and 40.22%, respectively, compared to the control (vehicle). Compared with cimetidine (48.29%), MEJP showed similar gastroprotective activity. CONCLUSIONS: This study demonstrated the gastroprotective activity of MEJP and contributes to validate the traditional use the species for gastric disorders and provides a pharmacological basis for its clinical potential.