Search

Aberration of the gastric mucosal barrier homeostasis circuit is one of the key features linked to the onset of gastric ulcers (GU). This work aimed to inspect the gastroprotective influence of dimethyl fumarate (DMF) on ethanol-induced GU in rats and to decipher the possible mechanisms entailed. Rats were pretreated with either DMF (80 mg/kg) or omeprazole (OMP) (20 mg/kg) by oral gavage for 2 weeks. After 24 h of starvation, ethanol (5 ml/kg, oral) was employed to trigger GU in rats, while carboxymethyl cellulose (CMC) was used as a control. Ethanol notably elevated both macroscopic and microscopic gastric damage. DMF and OMP exhibited similar effects on gastric ulcer healing. DMF intervention led to a substantial improvement in gastric insults. DMF significantly reduced ethanol-triggered gastric lesions, as manifested by decreased gastric secretion, acidity, ulcer surface area percent, reduced leukocyte incursion, and increased mucus percent. DMF upregulated miR-34a-5p expression concomitant with the suppression of high mobility group box1 (HMGB1) and inflammatory responses in gastric mucosal homogenate. DMF improved GU by restoring reduced antioxidant defense mechanisms through the coactivation of nuclear factor erythroid 2-related factor-2 (Nrf2), peroxisome proliferator-activated receptor gamma (PPARγ), and sirtuin1 (SIRT1), indicating the protective role of the PPARγ/SIRT1/Nrf2 pathway. Intriguingly, DMF mitigated apoptosis in ethanol-elicited GU. Taken together, this research implies the potential for the repurposing of DMF as an innovative gastroprotective medication to reestablish the balance of the gastric mucosal barrier via the attenuation of gastric inflammation, oxidative stress, and apoptosis., Competing Interests: Declaration of competing interest The authors declare no conflicts of interests relevant to this study., (Copyright © 2024. Published by Elsevier Inc.)

Gastric ulcer is a highly prevalent digestive tract disease across the world, which is recurrent and hard to cure, sometimes transforming into gastric cancer if left untreated, posing great threat to human health. To develop new medicines for gastric ulcer, we ran a series of screens with ethanol stress model in GES-1 cells, and we uncovered that lamivudine rescued cells from ethanol toxicity. Then, we confirmed this discovery using the well-established ethanol-induced gastric ulcer model in mice and our findings suggest that lamivudine can directly activate phosphoglycerate kinase 1 (PGK1, EC 2.7.2.3), which binds and stimulates superoxide dismutase 1 (SOD1, EC 1.15.1.1) to inhibit ferroptosis and ultimately improve gastric ulcer. Moreover, AAV-PGK1 exhibited comparable gastroprotective effects to lamivudine. The findings are expected to offer novel therapeutic strategies for gastric ulcer, encompassing both lamivudine and AAV-PGK1., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: We have applied for a patent based on the findings in the report, and we plan to benefit from the commercialization of the technology., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Equine Gastric Ulcer Syndrome (EGUS) occurs with variable prevalence in horses, donkeys, and mules. Due to the particularities of the mucous membranes, the syndrome is made up of Squamous Gastric Disease (ESGD) and Glandular Gastric Disease (EGGD). Given the multifactorial nature and multiple classification systems of the syndrome, significant differences have been reported between prevalence studies performed ante mortem, which are even more remarkable when compared with postmortem evaluations. This study aimed to determine the presence and grade of squamous gastric disease in horses, donkeys and mules immediately after slaughter. The postmortem examination considered the inspection of the squamous region (cardia, dorsal fundus, and margo plicatus) and the classification of the observed lesions. The general prevalence of ESGD in the entire population of study was 83.3 % (78 %, 89 %, and 83 % for horses, donkeys, and mules, respectively), compromising the margo plicatus in all cases. 75 % had more than 5 lesions and 50 % had deep lesions, lesions of varying severity and/or evidence of recent/active bleeding. The prevalence of ESGD was similar in horses, donkeys, and mules subjected to similar handling conditions prior to slaughter, including long-distance traveling, fasting, and stress factors., Competing Interests: Declaration of competing interest The authors declare that they have no know competing financial interest or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Gastric ulcer is a disturbing disease that impacts many people worldwide. Pioglitazone (Piog), a thiazolidinedione, and ligustrazine (Ligu), a natural component of Ligusticum chuanxiong possess gastroprotective properties. However, the underlying mechanism is not well elucidated. The present study aimed to investigate the gastroprotective effects of Piog (15 mg/kg, p.o.), Ligu (15 mg/kg, p.o.), and their combination against ethanol-induced gastric ulcer in rats. Omeprazole (10 mg/kg) was used as a standard. Pre-treatment for 7 days with Piog, Ligu, and (Piog+Ligu) effectively alleviated ethanol-predisposed oxidative stress and inflammation through restoring HO-1, GSH, and SOD tissue levels and decreasing elevated MDA, TNF-α, ICAM, I-NOS, and IL-1β contents. Moreover, Piog, Ligu, and (Piog+Ligu) markedly inhibited the ethanol-induced increase of gastric NF-KB and BAX. In contrast, this pre-treatment regimen significantly accelerated protein expression of SIRT1, Nrf2, and Bcl-2, along with autophagic proteins, ATG5 and Beclin. Interestingly, macroscopic, histopathological examination and mucin content were in harmony with previous results, where pre-treatment with Piog, Ligu, and (Piog+Ligu) showed a declined mucosal injury as evidenced by the remarkable decrease of the ulcer area percentage by 62.3%, 38.7%, and 91.2%, respectively, compared to the ethanol-ulcerated group. In conclusion, Piog and Ligu exhibited remarkable gastroprotective properties. Our study was the first to show that Piog, Ligu, and (Piog+Ligu) ameliorated oxidative stress, inflammation, and apoptosis and accelerated the autophagic process via the upregulation of the upstream SIRT1 protein. It is worth mentioning that future studies are needed to pave the way for the clinical use of Piog and Ligu as gastro-protective agents., (© 2024. The Author(s).)

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., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

We evaluate the value of oral contrast-enhanced gastric ultrasonography (OCUS) by comparing it with conventional gastroscopy in diagnosing and staging benign peptic ulcer. From July 2018 to December 2020, 44 patients with gastroscopy-confirmed benign peptic ulcers (a total of 45 ulcers were detected), who also received OCUS, were retrospectively reviewed. Each patient's ultrasound images were compared with gastroscopy and pathology findings. The characteristics of ultrasonic images of different stages of ulcer were analysed. A total of 43 ulcers were detected by OCUS in 44 patients with benign peptic ulcers. There were no false positive results among the OCUS exams, but two ulcers were misdiagnosed. OCUS for benign peptic ulcer staging also shows acceptable clinical practice results. OCUS is useful for detecting and staging benign peptic ulcer, and may be considered an alternative method for conventional gastroscopy. OCUS is especially useful in the follow-up of BPU treatment, but futher study is needed to improve the diagnostic accuracy of benign and malignant ulcers., (© 2024. The Author(s).)

Purpose: This study aimed to evaluate the morbidity associated with excisional biopsy in patients with spontaneous gastric perforation., Methods: A retrospective, single-center, observational study was performed. All consecutive patients with spontaneous gastric perforation who underwent surgical therapy were included. Outcomes were assessed concerning the performance of excisional biopsy., Results: A total of 135 adult patients were enrolled. Of these, 110 (81.5%) patients underwent excisional biopsy, while 17 (12.6%) did not. The remaining eight (5.9%) patients who underwent gastric resection were excluded from the analysis. Patients undergoing excisional biopsy developed significantly higher rates of postoperative complications (p = 0.007) and experienced more severe complications according to the Clavien-Dindo classification, particularly type III and above (p = 0.017). However, no significant differences were observed regarding in-hospital mortality, reoperation, suture dehiscence, or length of hospital stay., Conclusion: Excisional biopsy for gastric perforation has been shown to be associated with increased morbidity. Surgical closure followed by early endoscopic biopsy may be a superior approach for gastric perforation management to rule out malignancy., (© 2024. The Author(s).)

We studied the effect of enteral administration of GABA on the gastric mucosa in male Wistar rats (n=47) with modeled metabolic stress (food deprivation for 9 days with free access to water). The relative weights of the adrenal glands and thymus were determined, and histological examination of the stomach was performed. In control rats, modeling the metabolic stress was accompanied by the development of erosive damage to the gastric mucosa related to blood supply disturbances. Administration of GABA prevented erosions and exhibited a pronounced gastroprotective effect. Thus, administration of GABA can be a promising method for the prevention and treatment of erosive gastric lesions associated with metabolic stress., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

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., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

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., Competing Interests: Declaration of Competing interest We wish to confirm that there are no known conflicts of interest associated with this publication of “In vivo antiulcer activity of 7-O-methyl aromadendrin and sakuranetin isolated from Eucalyptus torquata L. via mitigating inflammatory and oxidative stress trails.” to be published in Journal of Ethnopharmacology. With the submission of this manuscript, I would like to undertake that the above-mentioned manuscript has not been published elsewhere, accepted for publication elsewhere or under editorial review for publication elsewhere; and that my Institute's (Faculty of Pharmacy, Cairo University) representative is fully aware of this submission., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Zingiberis rhizoma recens-/wine-/euodiae fructus-processed Coptidis Rhizoma (CR, zCR/wCR/eCR) are the commonly used processed products of CR in clinic. After being processed with different excipients, the efficacy of CR will change accordingly. I.e., wCR could resolve excessive heat of the upper energizer, zCR could eliminate gastric heat and harmonize the stomach, eCR could smooth the liver and harmonize the stomach. However, the underlying mechanisms were still unclear., Aim of the Study: To further verify the differential efficacy of the three processed CR products and compare the mechanisms on gastric ulcer., Material and Methods: First, a GU model, whose onset is closely related to the heat in stomach and the disharmony between liver and stomach, was established, and the therapeutic effects of zCR/wCR/eCR/CR were evaluated by pathologic observation and measurement of cytokine levels. Second, metabolomics analysis and network pharmacology were conducted to reveal the differential intervening mechanism of zCR/eCR on GU. Third, the predicted mechanisms from metabolomics analysis and network pharmacology were validated using western blotting, flow cytometry and immunofluorescence., Results: zCR/wCR/eCR/CR could alleviate the pathologic damage to varying degrees. In metabolomics research, fewer metabolic pathways were enriched in serum samples, and most of them were also present in the results of gastric tissue samples. The gastroprotective, anti-inflammatory, antioxidant, and anti-apoptotic effects of zCR/wCR/eCR/CR might be due to their interference on histidine, arachidonic acid, and glycerophospholipids metabolism. Quantitative results indicated that zCR/eCR had a better therapeutic effect than wCR/CR in treating GU. A comprehensive analysis of metabolomics and network pharmacology revealed that zCR and eCR exerted anti-GU effects via intervening in five core targets, including AKT, TNF, IL6, IL1B and PPARG. In the validation experiment, zCR/eCR could significantly reverse the abnormal expression of proteins related to apoptosis, inflammation, oxidative stress, gastric function, as well as the PI3K/AKT signaling pathways., Conclusion: zCR and eCR could offer gastroprotective benefits by resisting inflammation and apoptosis, inhibiting gastric-acid secretion, as well as strengthening gastric mucosal defense and antioxidant capacity. Integrating network pharmacology and metabolomics analysis could reveal the acting mechanism of drugs and promote the development of medications to counteract GU., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Gastric ulcer is a common disease affecting pigs worldwide, with a prevalence reported as high as 93%. The cause of porcine gastric ulcer is multifactorial, with Helicobacter suis (H. suis) being considered as the primary pathogenic factor. To date, prevalence of H. suis resulting in porcine gastric ulcer in Taiwan has not been investigated. In this study, we collected 360 pig stomachs from the slaughterhouses. In addition, stomach tissues from the 88 diseased pigs submitted for necropsy were divided into symptomatic and asymptomatic groups. Gastric lesions were scored, and polymerase chain reaction was used to determine the occurrence of gastric ulcer and the prevalence of H. suis. The positive rate of H. suis in the samples from slaughtered pigs was 49.7%, and both infection of H. suis and the presence of gastric lesions were prone to occur in autumn. The positive rates of H. suis infection in the symptomatic and asymptomatic groups were 59.1% and 31.8%, respectively. Moreover, the proportion of the samples with gastroesophageal ulcer in the symptomatic group was 68.2%, predominantly observed in growing pigs. The incidence of the samples from the slaughterhouses with gastroesophageal erosion to ulceration revealed a significant difference between H. suis -infected and H. suis -uninfected pigs; however, there is no significant difference in the samples of diseased pigs. In conclusion, H. suis infection was associated with gastric ulcer in slaughtered pigs, but it was not the primary cause of gastroesophageal ulcer in diseased pigs with clinical symptoms.

Background: Vanillic acid (VA; 4-hydroxy-3-methoxybenzoic acid) is a flavouring agent found in various natural sources such as olives, fruits, and green tea. While VA exhibits numerous pharmacological effects, its potential protective effects against gastric injury warrants further investigation. Therefore, the primary objective of this study is to elucidate investigate the gastroprotective properties of VA against ethanol-induced gastric injury., Methods and Results: Rats were orally administered either saline or VA at different doses (50, 100, and 200 mg/kg/day), with omeprazole (20 mg/kg) serving as a positive control, for fourteen consecutive days before ethanol administration. Blood and gastric tissue samples were collected one hour after ethanol administration for biochemical, molecular, and histological analyses. Pre-treatment with VA before ulcer induction alleviated both macroscopic and microscopic damage. It also increased antioxidant glutathione levels and decreased malondialdehyde and myeloperoxidase activity, along with reducing inflammatory markers such as tumour necrosis factor (TNF)-α, interleukin (IL)-6, and nuclear factor kappa B (NF-κB). Additionally, VA pre-treatment reversed the elevation of Bax mRNA expression and gastric caspase-3 levels induced by gastric damage. It also mitigated the reduction in Bcl-2 mRNA expression., Conclusion: These findings suggest that VA exerts protective effects against ethanol-induced gastric injury in rats. It achieves this by augmenting gastric antioxidant capacity and mitigating oxidative, inflammatory, and apoptotic damage., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Ethnopharmacological Relevance: Solenostemma argel is widely distributed in Africa & Asia with traditional usage in alleviating abdominal colic, aches, & cramps. This plant is rich in phytochemicals, which must be explored for its pharmacological effects., Purpose: Peptic Ulcer Disease (PUD) is the digestion of the digestive tube. PUD not only interferes with food digestion & nutrient absorption, damages one of the largest defensive barriers against pathogenic micro-organisms, but also impedes drug absorption & bioavailability, rendering the oral route, the most convenient way, ineffective. Omeprazole, one of the indispensable cost-effective proton-pump inhibitors (PPIs) extensively prescribed to control PUD, is showing growing apprehensions toward multiple drug interactions & side effects. Hence, finding a natural alternative with Omeprazole-like activity & limited side effects is a medical concern., Study Design: Therefore, we present Stemmoside C as a new gastroprotective phytochemical agent isolated from Solenostemma argel to be tested in upgrading doses against ethanol-induced gastric ulcers in mice compared to negative, positive, & reference Omeprazole groups., Methods: We carried out in-depth pharmacological & histopathological studies to determine the possible mechanistic pathway., Results: Our results showed that Stemmoside C protected the stomach against ethanol-induced gastric ulcers parallel to Omeprazole. Furthermore, the mechanistic studies revealed that Stemmoside C produced its effect using an orchestrated array of different mechanisms. Stemmoside C stimulates stomach defense by increasing COX-2, PGE-2, NO, & TFF-1 healing factors, IL-10 anti-inflammatory cytokine, & Nrf-2 & HO-1 anti-oxidant pathways. It also suppresses stomach ulceration by inhibiting leucocyte recruitment, especially neutrophils, leading to subsequent inhibition of NF-κBp65, TNF-α, IL-1β, & iNOS pro-inflammatory cytokines & JAK-1/STAT-3 inflammation-induced carcinogenicity cascade in addition to MMP-9 responsible for tissue degradation., Conclusion: These findings cast light on Stemmoside C's clinical application against gastric ulcer progression, recurrence, & tumorigenicity & concurrently with chemotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To improve the biological and toxicological properties of Mefenamic acid (MA), the galactosylated prodrug of MA named MefeGAL was included in polymeric solid dispersions (PSs) composed of poly(glycerol adipate) (PGA) and Pluronic® F68 (MefeGAL-PS). MefeGAL-PS was compared with polymeric solid formulations of MA (MA-PS) or a mixture of equal ratio of MefeGAL/MA (Mix-PS)., Methods: The in vitro and in vivo pharmacological and toxicological profiles of PSs have been investigated. In detail, we evaluated the anti-inflammatory (carrageenan-induced paw edema test), analgesic (acetic acid-induced writhing test) and ulcerogenic activity in mice after oral treatment. Additionally, the antiproliferative activity of PSs was assessed on in vitro models of colorectal and non-small cell lung cancer., Results: When the PSs were resuspended in water, MefeGAL's, MA's and their mixture's apparent solubilities improved due to the interaction with the polymeric formulation. By comparing the in-vivo biological performance of MefeGAL-PS with that of MA, MefeGAL and MA-PS, it was seen that MefeGAL-PS exhibited the same sustained and delayed analgesic and anti-inflammatory profile as MefeGAL but did not cause gastrointestinal irritation. The pharmacological effect of Mix-PS was present from the first hours after administration, lasting about 44 hours with only slight gastric mucosa irritation. In-vitro evaluation indicated that Mix-PS had statistically significant higher cytotoxicity than MA-PS and MefeGAL-PS., Conclusions: These preliminary data are promising evidence that the galactosylated prodrug approach in tandem with a polymer-drug solid dispersion formulation strategy could represent a new drug delivery route to improve the solubility and biological activity of NSAIDs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Proton-pump inhibitors (PPIs) prevent aspirin-associated gastric and duodenal mucosal damage. However, long-term use of PPIs can lead to various adverse reactions, such as gastric polyps and enterochromaffin-like cell hyperplasia. Current research indicates that the abovementioned adverse reactions are mainly related to hypergastrinemia. We investigated whether low-frequency administration of omeprazole could effectively repair aspirin-induced mucosal damage and reduce the increase in gastrin levels associated with long-term use of PPIs., Methods: Sprague‒Dawley rats were divided into four treatment groups: daily aspirin, daily aspirin and omeprazole once every day (qd), daily aspirin and omeprazole once every other day (qod), and daily aspirin and omeprazole once every three days (1/d3). After 15 days of feeding, blood samples were collected, and the stomachs of sacrificed rats were subjected to macroscopic, histological, and immunohistochemical studies. Moreover, in clinical practice, patients with peptic ulcers caused by aspirin took a standard dose of omeprazole (20 mg) every other day. Two months later, gastroscopy was performed to examine the healing of the ulcers., Results: Both the omeprazole qd and omeprazole qod administrations effectively prevented aspirin-induced gastric peptic ulcers, with no significant difference between the two groups in the inhibition of parietal cell secretion of gastric acid and cell apoptosis. However, omeprazole 1/d3 failed to completely prevent aspirin-induced gastric mucosal injury. Notably, the gastrin levels, cell proliferation ability and cholecystokinin B receptor expression of the omeprazole qd group were significantly higher than those of the omeprazole qod group. In clinical work, patients with peptic ulcers caused by aspirin were given a standard dose of omeprazole every other day, and their ulcers healed after 2 months, as observed by gastroscopy., Conclusions: Omeprazole administration once every other day can effectively prevent aspirin-induced peptic ulcers and reduce hypergastrinemia, which may reduce the long-term adverse effects of PPI treatment., (© 2024. The Author(s).)

Background: Indomethacin is an anti-inflammatory drug that causes ulcers on the gastric mucosa due to its use. Probiotic bacteria are live microorganisms, and it has been stated by various studies that these bacteria have antioxidant and anti-inflammatory effects. In this study, we investigated the possible protective effect of various types of probiotic bacteria (Lactobacillus rhamnosus, Lactobacillus fermentum, and Lactobacillus brevis) against acute gastric mucosal damage caused by indomethacin., Methods: Control group - Physiological saline was administered daily for 10 days. Indo group-Physiological saline was administered daily for 10 days. Ranitidine + Indo group 5 mg/kg ranitidine dose was administered daily for 5 days. On day 11, a single dose of 100 mg/kg of indomethacin was given to the same group. Probiotic + Indo group 1 ml/kg of oral probiotic bacteria was administered daily for 10 days. On day 11, a single 100 mg/kg dose of indomethacin was given. After the application, the rats were anesthetized with ketamine xylazine, killed under appropriate conditions, the abdominal cavity was opened and the stomach tissues were removed. The obtained gastric tissues were used in the biochemical and histopathological analyses discussed below. All data were statistically evaluated by one-way ANOVA using SPSS 20.00, followed by Duncan Post hoc test. The data were expressed as mean ± SD. P < 0.05 was considered statistically significant., Results: As a result, the administration of indomethacin caused gastric damage, stimulating oxidative stress, inflammation, and apoptosis. We found that the use of probiotic bacteria reduces oxidative stress (TOC), increases the activity of antioxidant enzymes (TAC), suppresses inflammation (IL-6 and Tnf-α), and inhibits apoptosis (Bax and Bcl-2) (P < 0.05)., Conclusion: Probiotic treatment can mitigate gastric damage and apoptosis caused by indomethacin-induced gastric damage in rats. Probiotic also enhances the restoration of biochemical oxidative enzymes as it has anti-inflammatory, antioxidant, and antiapoptotic properties., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The current study was designed to investigate the potential of a synthetic therapeutic agent for better management of pain and inflammation, exhibiting minimal to non-existent ulcerogenic effects. The effect of 1-(2-chlorobenzoyl)-3-(2,3-dichlorophenyl) thiourea was assessed through model systems of nociception and anti-inflammatory activities in mice. In addition, the ulcerogenic potential was evaluated in rats using the NSAID-induced pyloric ligation model, followed by histopathological and biochemical analysis. The test was conducted on eight groups of albino rats, comprising of group I (normal saline), groups II and III (aspirin® at doses of 100 mg/kg and 150 mg/kg, respectively), groups IV and V (indomethacin at doses of 100 mg/kg and 150 mg/kg, respectively), and groups VI, VII, and VIII (lead-compound at 15 mg/kg, 30 mg/kg and 45 mg/kg doses, respectively). Furthermore, molecular docking analyses were performed to predict potential molecular target site interactions. The results showed that the lead-compound, administered at doses of 15, 30, and 45 mg/kg, yielded significant reductions in chemically and thermally induced nociceptive pain, aligning with the levels observed for aspirin® and tramadol. The compound also effectively suppressed inflammatory response in the carrageenan-induced paw edema model. As for the ulcerogenic effects, the compound groups displayed no considerable alterations compared to the aspirin® and indomethacin groups, which displayed substantial increases in ulcer scores, total acidity, free acidity, and gastric juice volume, and a decrease in gastric juice pH. In conclusion, these findings suggest that our test compound exhibits potent antinociceptive, anti-inflammatory properties and is devoid of ulcerogenic effects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Antidepressant duloxetine has been shown protective effect on indomethacin-induced gastric ulcer, which was escorted by inflammation in the gastric mucosa. Cytokines are the principal mediators of inflammation. Thus, by screening the differential expression of cytokines in the gastric mucosa using cytokine array at 3 h after indomethacin exposure, when the gastric ulcer began to format, we found that indomethacin increased cytokines which promoted inflammation responses, whereas duloxetine decreased pro-inflammatory cytokines increased by indomethacin and increased RANTES expression. RANTES was consistently increased by pretreated with both 5 mg/kg and 20 mg/kg duloxetine at 3 h and 6 h after indomethacin exposure in male rats. Selective blockade of RANTES-CCR5 axis by a functional antagonist Met-RANTES or a CCR5 antagonist maraviroc suppressed the protection of duloxetine. Considering the pharmacologic action of duloxetine on reuptake of monoamine neurotransmitters, we examined the serotonin (5-HT), norepinephrine and dopamine contents in the blood and discovered 20 mg/kg duloxetine increased 5-HT levels in platelet-poor plasma, while treatment with 5-HT promoted expression of RANTES in the gastric mucosa and alleviated the indomethacin-induced gastric injury. Furthermore, duloxetine activated PI3K-AKT-VEGF signaling pathway, which was regulated by RANTES-CCR5, and selective inhibitor of VEGF receptor axitinib blocked the prophylactic effect of duloxetine. Furthermore, duloxetine also protected gastric mucosa from indomethacin in female rats, and RANTES was increased by duloxetine after 6 h after indomethacin exposure too. Together, our results identified the role of cytokines, particularly RANTES, and the underlying mechanisms in gastroprotective effect of duloxetine against indomethacin, which advanced our understanding in inflammatory modulation by monoamine-based antidepressants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Gastric ulcers are one of the most prevalent gastrointestinal disorders. The current study investigated the antioxidant and anti-inflammatory effects of selenium (Se) and lecithin (Lec) alone and in combination against ethanol-induced gastric ulcers in mice, and their ability to modulate insulin-like growth factor-1 (IGF-1)/ Phosphatase and tensin homologue deleted on chromosome 10 (PTEN)/ Protein kinase B (Akt)/ Forkhead box O3a (FoxO3a) signaling. The mice were divided into normal, ethanol, Se + ethanol, Lec + ethanol, Se + Lec + ethanol, and omeprazole + ethanol groups. Treatment with the selected doses was continued for 14 days before a single dose of absolute ethanol (5 ml/kg body weight) was administered to induce gastric ulcers in mice. The results showed that pretreatment with Se and Lec combination effectively decreased both the macro- and microscopic gastric lesions and increased the protection index compared to the ethanol group. Remarkably, the Se and Lec combination decreased the levels of reactive oxygen species, malondialdehyde, and cytochrome c and increased glutathione, glutathione peroxidase, and thioredoxin reductase activities in gastric tissues. The Se and Lec combination increased prostaglandin E2 and interleukin-10 levels but decreased tumor necrosis factor-α, interleukin-6 and interleukin-1β levels compared to either treatment alone. Interestingly, this combination decreased the expression of IGF-1, p-Akt, and FoxO3a proteins and increased PTEN expression in gastric tissues. The gastric tissues examination by hematoxylin and eosin staining confirmed these results. Therefore, the Se and Lec combination showed superior protective effects against ethanol-induced gastric ulcers in mice, compared to either treatment alone, through antioxidant, and anti-inflammatory activities, in addition to modulating IGF-1/PTEN/Akt/FoxO3a pathway signaling., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Recently, Enterococcus has been shown to have gastric protective functions, and the mechanisms by which Enterococcus modulates gastric function are still being investigated. Herein, we investigated how Enterococcus faecium (Efm) and E. faecium -derived extracellular vesicles (EVs) (EfmEVs) exert protective effect against ethanol-induced gastric injury by investigating the effect of EfmEVs on gastric mucosal ulcer scoring, histological lesion, mucosal glycoprotein production, acidity, anti-oxidative function, and inflammatory responses in rat. Pretreatment with Efm showed significant reduction of ethanol-induced gastric injury, as evidenced by the lowering of ulcer index, histological lesion, gastric pH, and inflammatory responses and the enhancement of mucosal glycoprotein production and anti-oxidative function. Further functional studies on three bioactive components [inactivated Efm, EfmEVs (EVs), and EV-free supernatants] of the bacterial culture showed that EVs are mostly responsible for the gastroprotective effect. Moreover, EV secretion is beneficial for the gastroprotective effect of Efm. Hence, EVs mediated the protective effect of Efm against ethanol-induced gastric injury by lowering inflammatory responses and enhancing anti-oxidative function and may be a potent anti-inflammatory and anti-oxidative strategy to alleviate hyperinflammatory gastrointestinal tract conditions.IMPORTANCEThis study indicated that Enterococcus faecium provided a protective effect against rat gastric injury, which involved improvement of the mucosal glycoprotein production, anti-oxidative function, and inflammatory responses. Furthermore, we confirmed that three bioactive components (inactivated Efm, extracellular vesicles, and EV-free supernatants) of E. faecium culture also contributed to the gastroprotective effect. Importantly, E. faecium -derived EVs showed an effective impact for the gastroprotective effect., Competing Interests: The authors declare no conflict of interest.

Background: Caustic ingestion is associated with long-term sequelae like esophageal stricture, gastric cicatrization, and long-term risk of dysplasia or even carcinoma. However, only a few small studies have explored histopathological aspects of caustic-induced esophageal/gastric injury., Materials and Methods: We retrospectively evaluated specimens of patients undergoing surgery due to caustic ingestion-related complications from 2008 to 2020. Pathological examination was conducted by two independent gastro-pathologists to evaluate the extent and depth of the caustic injury, presence or absence of tissue necrosis, type and degree of inflammation, or presence of any dysplastic cells., Results: A total of 54 patients underwent surgical exploration during the inclusion period and complete details of 39 specimens could be retrieved. The mean age of the included patients was 28.66 ± 9.31 years and 25 (64.1%) were male. The majority of patients (30; 76.9%) had a history of caustic ingestion more than three months before the surgery and the presence of long or refractory stricture was the most common indication for the surgery (20; 51.28%). In the resected specimen, a majority of patients had superficial esophageal or gastric ulcer (90.6%; 60.0%), transmural inflammation (68.8%; 65.6%), transmural fibrosis (62.5%; 34.4%), and hypertrophied muscularis mucosa (78.13%; 53.3%). However, none of the patients had dysplasia in the resected esophageal or gastric specimens., Conclusion: Caustic ingestion leads to mucosal ulceration, transmural inflammation, and transmural fibrosis which might be the reason for refractory stricture in such patients., (Copyright © 2024 Copyright: © 2024 Indian Journal of Pathology and Microbiology.)

The purpose of this study was to evaluate the effects of syringic acid, an anti-oxidant, on indomethacin induced gastric ulcers in rats. Experimental groups were control, ulcer, ulcer treated with 20 mg/kg esomeprazole (a proton pump inhibitor that reduces acid secretion), and ulcer treated with 100 mg/kg syringic acid. Rats were pretreated with esomeprazole or syringic acid two weeks before ulcer induction. Our histopathological observations showed that either syringic acid or esomeprazole attenuated the severity of gastric mucosal damage. Moreover, syringic acid and esomeprazole pretreatments alleviated indomethacin-induced damage by regulating oxidative stress, inflammatory response, the level of transforming growth factor-β (TGF-β), expressions of COX and prostaglandin E 2 , cell proliferation, apoptosis and regulation of the NF-κB signaling pathway. We conclude that either esomeprazole or syringic acid administration protected the gastric mucosa from harmful effects of indomethacin. Syringic acid might, therefore be a potential therapeutic agent for preventing and treating indomethacin-induced gastric damage.

The study presents a significant advancement in drug delivery and therapeutic efficacy through the successful synthesis of Gliricidia sepium(Jacq.) Kunth. ex. Walp., stem zinc oxide nanoparticles(GSS ZnONPs). The phenolic compounds present in Gliricidia sepium stem (GSS) particularly vanillic acid, apegnin-7-O-glucoside, syringic acid, and p-coumaric acid which were identified by HPLC. These compounds shown antioxidant and anti-inflammatory properties. GSS ZnONPs demonstrate pronounced gastroprotective effects against ethanol-induced gastritis, evidenced by the reduction in gastric lesions and mucosal injury upon its treatment. Histopathological evaluation and immunohistochemical analysis of nuclear factor erythroid 2-related factor 2 (Nrf2) expression further validate these results, revealing the amelioration of ethanol-induced gastritis and improved gastric tissue condition due to their treatment. Noteworthy is the dose-dependent response of GSS ZnONPs, showcasing their efficacy even at lower doses against ethanol-induced gastritis which is confirmed by different biomarkers. These findings have substantial implications for mitigating dosage-related adverse effects while preserving therapeutic benefits, offering a more favorable treatment approach. This study aims to investigate the potential gastroprotective activity of GSS ZnONPs against gastritis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The present study was designed to assess Tradescantia spathacea's antidiabetic ability, as well as the antiulcer activity of the entire plant extract. The diabetic condition was evaluated using Streptozotocin's oral glucose tolerance test, diabetes-alloxan and diabetes-models. Antiulcer activities were observed in rats where gastric ulcers were either caused by oral administration of ethanol, or pyloric ligation. Standards include ranitidine, glibenclamide and sucralfate. In all models, the blood glucose levels of animals treated with the test extract were found to be significantly lower compared to diabetic care. Similarly, in all models, the ulcer index in the animals treated with the test extract was found to be significantly lower relative to the animals under vehicle supervision. Our findings say T. Spathacea extract has essential anti-diabetic properties, as well as antiulcer properties.

Gastric ulcer (GU) is a serious upper gastrointestinal tract disorder that affects people worldwide. The drugs now available for GU treatment have a high rate of relapses and drug interactions, as well as mild to severe side effects. As a result, new natural therapeutic medications for treating GU with fewer negative side effects are desperately needed. Because of quercetin's (QCT) diverse pharmacological effects and unique structural features, we decided to semi-synthesize new QCT derivatives and test them for antiulcer activity. Docking assays were performed on the synthesized compounds to determine their affinity for TLR-4/MD-2, MyD88/TIR, and NF-κB domains, an important inflammatory pathway involved in GU development and progression. Mice were given oral famotidine (40 mg/kg/day), QCT, QCT pentamethyl (QPM), or QCT pentaacetyl (QPA) (50 mg/kg/day) for 5 days before GU induction by a single intraperitoneal injection of indomethacin (INDO; 18 mg/kg). QPM and QPA have a stronger binding affinity for TLR-4/MD-2, MyD88/TIR and NF-κB domains than QCT. In comparison, they demonstrated the greatest reduction in ulcer score and index, gastric MDA and nitric oxide (NO) contents, MyD88 and NF-κB expressions, and gastric TLR-4 immunostaining. They also enhanced the levels of GSH, CAT, COX-1, and COX-2 in the gastric mucosa, as well as HO-1 and Nrf2 expression, with histological regression in gastric mucosal lesions, with QPA-treated mice demonstrating the best GU healing. QPA is safe against all of the target organs and adverse pathways studied, with good ADME properties. However, further in vitro experiments are necessary to demonstrate the inhibitory effects of QPM and QPA on the protein targets of interest. In addition, preclinical research on its bioavailability and safety is essential before clinical management can be undertaken. Overall, the new QPA derivative could one day serve as the basis for a new class of potential antiulcer drugs., Competing Interests: Declaration of competing interest The authors declare no conflict of interest. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study investigated the role of causative infectious agents in ulceration of the non-glandular part of the porcine stomach (pars oesophagea). In total, 150 stomachs from slaughter pigs were included, 75 from pigs that received a meal feed, 75 from pigs that received an equivalent pelleted feed with a smaller particle size. The pars oesophagea was macroscopically examined after slaughter. (q)PCR assays for H. suis, F. gastrosuis and H. pylori-like organisms were performed, as well as 16S rRNA sequencing for pars oesophagea microbiome analyses. All 150 pig stomachs showed lesions. F. gastrosuis was detected in 115 cases (77%) and H. suis in 117 cases (78%), with 92 cases (61%) of co-infection; H. pylori-like organisms were detected in one case. Higher infectious loads of H. suis increased the odds of severe gastric lesions (OR = 1.14, p = 0.038), while the presence of H. suis infection in the pyloric gland zone increased the probability of pars oesophageal erosions [16.4% (95% CI 0.6-32.2%)]. The causal effect of H. suis was mediated by decreased pars oesophageal microbiome diversity [-1.9% (95% CI - 5.0-1.2%)], increased abundances of Veillonella and Campylobacter spp., and decreased abundances of Lactobacillus, Escherichia-Shigella, and Enterobacteriaceae spp. Higher infectious loads of F. gastrosuis in the pars oesophagea decreased the odds of severe gastric lesions (OR = 0.8, p = 0.0014). Feed pelleting had no significant impact on the prevalence of severe gastric lesions (OR = 1.72, p = 0.28). H. suis infections are a risk factor for ulceration of the porcine pars oesophagea, probably mediated through alterations in pars oesophageal microbiome diversity and composition., (© 2024. The Author(s).)

Equine gastric ulcer syndrome (EGUS) is currently one of the more frequent diseases in horses. We aimed to identify changes in the salivary proteome in horses with EGUS at diagnosis and after successful treatment by using gel proteomics. Saliva samples were collected from nine horses with EGUS before and after treatment and nine matched healthy controls. SDS-PAGE (1DE) and two-dimensional gel electrophoresis (2DE) were performed, and significantly different protein bands and spots were identified by mass spectrometry. Horses with EGUS had increases in proteins such as adenosine deaminase (ADA), triosephosphate isomerase, keratins and immuno-globulin heavy constant mu and decreases in carbonic anhydrase (CA), albumin and prolactin-induced protein. These changes would indicate various physiopathological mechanisms involved in this disease, such as the activation of the immune system, decreased stomach defence mechanisms and inflammation. The treated horses presented lower expression levels of thioredoxin (TRX) after a successful treatment, in proteomics analysis and also measured with a commercially available ELISA kit. Overall, horses with EGUS have protein changes in their saliva when measured with gel proteomics compared with healthy horses, and they also showed changes after successful treatment. These proteins could be potential biomarkers for detection and monitoring treatment response in EGUS., Competing Interests: Declaration of Competing Interest The authors of this manuscript have no financial or personal relationships that could potentially influence the content and findings presented in the manuscript. We confirm that there are no affiliations with organizations or entities that have a direct interest in the subject matter discussed in the article. Our commitment to transparency and integrity in research is paramount, and we assure you that the research was conducted objectively and without any external influences that could compromise the validity of the results. We adhere to the highest ethical standards in the preparation and submission of this manuscript to Research in Veterinary Science., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Ethnopharmacological Relevance: The utilization of plants with therapeutic properties in traditional medicine has a longstanding practice. Among them, the well-known Allium cepa L. commonly known as onion has been valued for its anti-inflammatory and antioxidant potential in the treatment of various ailments, including gastric ulcers., Aim of the Study: This study investigated the gastroprotective potential of red onion peel extract and its fractions in a rat model of ethanol-induced gastric ulcer. Moreover, their phytochemical profiles were compared to identify the active metabolites., Materials and Methods: Mass spectrometry-based metabolomics and chemometrics were performed for phytochemical analysis. Ethanol-induced gastric ulcer model was used to assess the gastroprotective activity. Nine groups of rats were allocated as follows: Group 1 was the normal control; Group 2 rats were used as a positive control/model and received 1 mL of absolute ethanol; and Group 3 rats were treated with famotidine at a dose of 20 mg/kg orally. Group 4 and 5 rats were treated with total acidified ethanolic extract (T1, T2). Group 6 and 7 rats were treated with anthocyanins-rich fractions (P1, P2). Groups 8 and 9 were the flavonoids-rich fraction (S1, S2) treatment. Prior to scarification, the ulcer index in mm was obtained from gastric tissues photographed beside a ruler with further analysis using ImageJ software., Results: Seventy key major and discriminatory metabolites were identified including flavonoids, anthocyanins, phenolic acids, and miscellaneous compounds. The examined extract and its fractions significantly reduced the ulcer index and inflammatory cytokines via downregulating HMGB-1/NF-κB. Also, they augmented the expression of Nrf2/HO-1 and reduced NOX1/4 mRNA expression. Moreover, there was a significant reduction in the oxidative stress and apoptotic biomarkers as well as a noticeable enhancement in histopathological changes of the stomach tissues., Conclusion: Red onion peels have a promising dose dependent gastroprotective potential in alcohol-induced ulcers via modulating Nrf2/HO-1 and HMGB-1/NF-κB trajectories. This highlights the potential of red onion peels in treating gastric ulcers., Competing Interests: Declaration of competing interest We wish to confirm that there are no known conflicts of interest associated with this publication of “Gastroprotective Potential of Red Onion (Allium cepa L.) Peel in Ethanol-Induced Gastric Injury in Rats: Involvement of Nrf2/HO-1 and HMGB-1/NF-κB Trajectories” to be published in Journal of Ethnopharmacology. With the submission of this manuscript I would like to undertake that the above mentioned manuscript has not been published elsewhere, accepted for publication elsewhere or under editorial review for publication elsewhere; and that my Institute's (Faculty of Pharmacy, Cairo University) representative is fully aware of this submission., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Huang-Qi-Jian-Zhong-Tang (HQJZT) is a canonical traditional Chinese medicine (TCM) formula that has been widely used in both the prevention and treatment of gastrointestinal diseases, including gastric ulcer, duodenal ulcer, and chronic atrophic gastritis, in China., Aim of the Study: In the present study, we investigated the gastroprotective potential of HQJZT in a rat model of indomethacin (IND)-induced gastric ulcer and explained the biochemical, cellular, and molecular mechanisms involved., Materials and Methods: Observations were conducted at the macroscopic level to ascertain the ulcer index (UI) and the curative index (CI). Histopathological examinations were conducted, and a microscopic score (MS) was computed. The gastric juice volume, total acidity, pH value, and pepsin activity were quantified. Antioxidant and oxidative parameters were assessed, namely GSH, CAT, SOD, and MDA content. The RFLSI Pro instrument was employed to measure the blood flow within the gastric mucosa continuously. The mRNA levels of the inflammatory cytokines were assessed using droplet digital PCR (ddPCR). Molecular docking was employed to examine the interaction between representative active components of HQJZT and the binding sites associated with the NF-κB and STAT signaling pathways. The protein expression and localization of p-JAK, p-STAT, p-IκBβ, and p-NF-κB were evaluated through immunofluorescence analysis., Results: The administration of HQJZT treatment demonstrated a significant reduction in gastric lesions induced by IND, leading to a notable decrease in the UI. Additionally, HQJZT treatment significantly decreased gastric juice volume, acidity, and pepsin activity, accompanied by increased pH value. IND-treated stomachs exhibited severe hemorrhagic necrosis, submucosal edema, and epithelial cell destruction. However, the administration of HQJZT effectively counteracted these pathological changes. Furthermore, HQJZT administration significantly increased blood flow to the gastric mucosa. HQJZT enhanced antioxidant defenses and modulated oxidative stress by increasing SOD, CAT, and GSH activities while reducing MDA levels. Moreover, HQJZT reversed IND-induced increases in mRNA expression levels of inflammatory cytokines. Molecular docking analysis revealed that the representative active components of HQJZT could bind to the NF-κB and STAT signaling pathways. In addition, immunofluorescence microscopy revealed that HQJZT markedly attenuated the phosphorylation of IκΒβ, NF-κB, JAK, and STAT., Conclusions: The therapeutic and protective effect of HQJZT on gastric ulcers is attributed to its ability to suppress gastric acid secretion, enhance antioxidative defenses and blood flow, mitigate proinflammatory cytokines, and inhibit the activation of NF-κB and STAT signaling pathways., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In recent times, the methods used to evaluate gastric ulcer healing worldwide have been based on visual examinations and estimating ulcer dimensions in experimental animals. In this study, the protective effect of rhodanine and 2,4-thiazolidinediones scaffolds compared to esomeprazole was investigated in an ethanol model of stomach ulcers in rats. Pretreatment with experimental treatments or esomeprazole prevented the development of ethanol-induced gastric ulcers. The severity of the lesions and injuries was significantly lower than that of vehicle (10% Tween 80) treated rats. Significant and excellent results were obtained with the compound 6 group, with inhibition percentage and ulcer area values of 97.8% and 12.8 ± 1.1 mm 2 , respectively. Synthesized compounds 2, 7 and 8 exhibited inhibition percentages and ulcer areas of 94.3% and 31.2 ± 1.1 mm 2 , 91. 3% and 48.1 ± 0. 8 mm 2 , 89. 5% and 57. 6 ± 1. 2 mm 2 , and 89. 1% and 60.3 ± 0. 8 mm 2 , respectively. These biological outcomes are consistent with the docking studies in which Compounds 7 and 8 showed remarkable binding site affinities toward human H+/K+-ATPase α protein (ID: P20648), rat H+/K+-ATPase α protein (ID: P09626), and Na+/K+-ATPase crystal structure (PDB ID:2ZXE) with binding site energies of - 10.7, - 9.0, and - 10.4 (kcal/mol) and - 8.7, - 8.5, and - 8.0 (kcal/mol), respectively. These results indicate that these test samples were as effective as esomeprazole. Likewise, immunohistochemical staining of antiapoptotic (BCL2) and tumor suppressor (P53) proteins showed strong positive marks in the10% Tween 80- treated group, opposing the mild staining results for the esomeprazole-treated group. Similarly, the staining intensity of the group treated with Compounds 2-8 was variable for both proteins., (© 2024. The Author(s).)

Introduction: Endoscopic diagnosis is essential for predicting the curability of early gastric cancer (EGC; R0 resection) before treatment, but the relationship between ulcerative lesions and clinical outcomes remains unclear. We aimed to investigate the effect of proton pump inhibitor (PPI) or potassium-competitive acid blocker (P-CAB) on the morphological changes of ulcerative EGCs and its relevance to the clinical outcomes., Methods: Altogether, 143 patients with differentiated ulcerative EGC that were resected by endoscopic submucosal dissection were retrospectively identified and divided into the following two cohorts depending on their PPI/P-CAB administration status: PPI/P-CAB (n = 76) and non-PPI/P-CAB (n = 67) cohorts. Furthermore, in each cohort, the patients were further divided into the improved and unimproved subgroups based on the ulcerative changes., Results: In the PPI/P-CAB cohort, the deep submucosal invasion and lymphovascular invasion rates were significantly higher in the unimproved subgroup than in the improved subgroup, resulting in a significantly lower R0 resection rate. Contrarily, no significant differences were found between the two subgroups in the non-PPI/P-CAB cohort. The significance of PPI/P-CAB administration was observed only in the ulcerative EGCs with open-type atrophy (R0 resection rate; improved vs. unimproved, 90.9% vs. 48.0%, p = 0.001). When the finding of improved ulcer with PPI/P-CAB administration was used as the indication of endoscopic resection in ulcerative EGCs with open-type atrophy, high sensitivity (78.9%) and accuracy (76.3%) rates for the curability were observed, which were higher than those of conventional endoscopic diagnosis alone (p = 0.021)., Conclusion: PPI or P-CAB administration might contribute to the potential selection of ulcerative EGCs, enabling endoscopic curative resection., (© 2024 S. Karger AG, Basel.)

Background: There are patents available related to fermented food and beverages which enhance to human health. Citrus limetta (Mosambi) has a high content of flavonoids and exhibits antioxidant activity, which could stimulate the digestive system and be useful for gastroprotective activity. It supports digestion by neutralizing the acidic digestive juices and reducing gastric acidity., Objective: This study explored the potential of using waste peel extract from Citrus limetta to prevent ulcers. The study specifically sought to assess the anti-ulcer properties of fermented and non-fermented extracts and compare them. Further, the study looked at the potential benefits of treating or preventing ulcers with Citrus limetta waste peels and whether fermentation affected the efficacy of the treatment., Methods: Thirty female Wistar albino rats were equally distributed into five different groups. Group 1 received distilled water (20 ml/kg/b.w); Group 2 received indomethacin (mg/kg/b.w); Group 3 received omeprazole (20 mg/kg/b.w); Group 4 received aqueous extract of Mosambi peel (400 mg/kg/b.w) and Group 5 received fermented product of extract of Mosambi peel (400 mg/kg/b.w)., Results: Findings explored that, compared to non-fermented citrus fruit juice, biofermented exhibited less gastric volume (1.58 ± 0.10 ml vs. 1.8 ± 0.14 ml), reduced MDA levels (355.23 ± 100.70 μmol/mg protein vs. 454.49 ± 155.88 μmol/mg protein), and low ulcer index (0.49 ± 0.07 vs. 0.72 ± 0.14)., Conclusion: The results suggest that the bio-fermented product of Citrus limetta peel has better anti-ulcer potential against peptic ulcer induced by indomethacin in Wistar albino rats compared to non-fermented., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Gastric ulcer healing is impaired in both hypothyroid and hyperthyroid conditions.  Thyroid hormones regulate growth, energy metabolism and mitochondrial oxidative metabolism. Xenobiotics have been documented to negatively impact the thyroid gland at high doses but the redox and cellular interactions at low doses during wound healing process remains unclear. Potassium bromate has been documented to be toxic at high doses but there is dearth of information on its activities at a low dose in varied thyroid states which was evaluated in this study. 60 male Wistar rats (g, n=10) were randomised into 2 conditions: Normal, ulcerated untreated, ulcerated treated with 12.5mg/kg p.o KBrO3 and thyroidectomised groups: thyroidectomised ulcerated, thyroidectomised ulcer treated with KBrO3 and thyroidectomised treated with thyroxine (100µg/kg) Total thyroidectomy was used to model hypothyroidism, and ischaemia-reperfusion-induced gastric ulcers were monitored for healing. Daily body weights, Levels of thyroxine, Gastric mucin content, redox and sodium pump activity were examined alongside other markers of hepatic and haematological toxicity by days 3 and 7 post ulceration. Data were analysed using descriptive statistics and ANOVA α 0.05. The bromate-exposed hypothyroid rats showed increased gastric ulcer healing potential with reduced gastric epithelial oedema and inflammation; hepatic steatosis, and periportal inflammation. Haematological variables and markers of hepatic functions were normal. There were reduced levels of gastric and hepatic malondialdehyde levels. Thyroxine and potassium bromate treatment resolved the redox and cellular toxicity possibly via increasing catalase and sulfhydryl levels and increased Na+ K+ pump activity. We conclude that potassium bromate enhanced gastric ulcer healing in hypothyroid state, similar to thyroxine treatment.

Equine glandular gastric disease (EGGD) is a common disease among athletic horses that can negatively impact health and performance. The pathophysiology of this EGGD remains poorly understood. Previous studies using controlled populations of horses identified differences in the gastric glandular mucosal microbiome associated with disease. The objective of this study was to compare the gastric microbiome in horses with EGGD and those without across multiple barns and differing management practices. We hypothesized that alterations in the microbiome of the gastric glandular mucosa are associated with EGGD. A secondary objective was to perform a risk factor analysis for EGGD using the diet and management data collected. Microbial populations of biopsies from normal pyloric mucosa of horses without EGGD (control biopsies), normal pyloric mucosa of horses with EGGD (normal biopsies) and areas of glandular mucosal disruption in horses with EGGD (lesion biopsies) were compared. Lesion biopsies had a different microbial community structure than control biopsies. Control biopsies had a higher read count for the phylum Actinomycetota compared to lesion biopsies. Control biopsies also had an enrichment of the genera Staphylococcus and Lawsonella and the species Streptococcus salivarius. Lesion biopsies had an enrichment of the genera Lactobacillus and Actinobacillus and the species Lactobacillus equigenerosi. These results demonstrate differences in the gastric glandular microbiome between sites of disrupted mucosa in horses with EGGD compared to pyloric mucosa of horses without EGGD. Risk factor analysis indicated that exercise duration per week was a risk factor for EGGD., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: HEB has previously received (greater than five years ago) other grant funding and performed consultancy work for Boehringer Ingelheim Animal Health. The other authors (LJP, FMA, ACE, ZM, MLK, MPS) have declared that no competing interests exist., (Copyright: © 2023 Paul et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Gastric lesions have several aetiologies, among which stress is the most prominent. Therefore, identification of new therapies to prevent stress is of considerable importance. Alpha-ketoglutarate (α-kg) several beneficial effects and has shown promise in combating oxidative stress, inflammation, and premature aging. Thus, this study aimed to evaluate the protective effect of α-kg in a gastric damage model by water-immersion restraint stress (WIRS). Pretreatment with α-kg decreased stress-related histopathological scores of tissue oedema, cell loss, and inflammatory infiltration. The α-kg restored the percentage of type III collagen fibres. Mucin levels were preserved as well as the structure and area of the myenteric plexus ganglia were preserved after pretreatment with α-kg. Myeloperoxidase (MPO) levels and the expression of pro-inflammatory cytokines (TNF-α and IL-1β) were also reduced following α-kg pretreatment. Decreased levels of glutathione (GSH) in the stress group were restored by α-kg. The omeprazole group was used as standard drug e also demonstrated improve on some parameters after the exposition to WIRS as inflammatory indexes, GSH and mucin. Through this, was possible to observe that α-kg can protect the gastric mucosa exposed to WIRS, preserve tissue architecture, reduce direct damage to the mucosa and inflammatory factors, stimulate the production of type III collagen and mucin, preserve the myenteric plexus ganglia, and maintain antioxidant potential. Due to, we indicate that α-kg has protective activity of the gastric mucosa, demonstrating its ability to prevent damage associated with gastric lesions caused by stress., Competing Interests: Declaration of competing interest The authors declare that there are no known competing financial interests or personal relationships that could influence the work of this article., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Gintonin, newly extracted from ginseng, is a glycoprotein that acts as an exogenous lysophosphatidic acid (LPA) receptor ligand. This study aimed to demonstrate the in vivo preventive effects of gintonin on gastric damage. ICR mice were randomly assigned to five groups: a normal group (received saline, 0.1 mL/10 g, p.o.); a control group (administered 0.3 M HCl/ethanol, 0.1 mL/10 g, p.o.) or indomethacin (30 mg/kg, p.o.); gintonin at two different doses (50 mg/kg or 100 mg/kg, p.o.) with either 0.3 M HCl/ethanol or indomethacin; and a positive control (Ranitidine, 40 mg/kg, p.o.). After gastric ulcer induction, the gastric tissue was examined to calculate the ulcer index. The expression of gastric damage markers, such as tumor necrosis factor (TNF)-α, cyclooxygenase 2 (COX-2), and LPA2 and LPA5 receptors, were measured by Western blotting. Interleukin-6 (IL-6) and prostaglandin E2 (PGE2) levels were measured by enzyme-linked immunosorbent assay. The platelet endothelial cell adhesion molecule (PECAM-1), Evans blue, and occludin levels in gastric tissues were measured using immunofluorescence analysis. Both HCl/ethanol- and indomethacin-induced gastric ulcers showed increased TNF-α, IL-6, Evans blue permeation, and PECAM-1, and decreased COX-2, PGE2, occludin, and LPA5 receptor expression levels. However, oral administration of gintonin alleviated the gastric ulcer index induced by HCl/ethanol and indomethacin in a dose-dependent manner. Gintonin suppressed TNF-α and IL-6 expression, but increased COX-2 expression and PGE2 levels in mouse gastric tissues. Gintonin intake also increased LPA5 receptor expression in mouse gastric tissues. These results indicate that gintonin can play a role in gastric protection against gastric damage induced by HCl/ethanol or indomethacin.

Background: A gastric ulcer is a painful lesion of the gastric mucosa that can be debilitating or even fatal. The effectiveness of several plant extracts in the therapy of this illness has been demonstrated in traditional pharmacopoeias., Aim: this study was aimed to see if propolis, ginseng in normal or nano form, and amygdalin might help in preventing the ulcerative effects of absolute ethanol., Methods: Gastroprotective properties of pretreatments before ethanol gavage in rats were compared to omeprazole. The ulcer and stomach parameters (ulcerated regions) were measured (mm 2 ), ulcer inhibition percentage, the stomachs were assessed macroscopically with gastric biopsy histological examinations., Results: Amygdalin, normal and nano ginseng, nano propolis followed by propolis all showed great efficacy in protecting the cyto-architecture and function of the gastric mucosa. The number of ulcerated sites was greatly reduced, and the percentage of stomach protection was increased. Histopathological examination had confirmed great protective effects of the nanoformulations followed by amygdalin. The protection and healing rate was completed to about 100% in all tested materials while ulcer areas were still partially unhealed in normal propolis and omeprazole. Quantitative assay of the m-RNA levels Enothelin 1(ET-1), leukotriene4 (LT-4), and caspase 3(Cas-3) genes and Histamine were done and revealed significant up-regulations in ethanol group and the maximum protective effect was reported with ginseng nano, moreover the histamine content was significantly decreased with nano- formulated extracts., Conclusion: Amygdalin and the nanoformulated ginseng and propolis had exhibited a marked protective effect against the ulcerative toxic effects of ethanol., (© 2023. The Author(s).)

This study demonstrated the effects of semi-solid enzymolysis on physicochemical properties of fruiting body powders and polysaccharides from Hericium erinaceus and protective effects on gastric mucosal injury. Semi-solid enzymolysis could reduce the particle size, change the microstructure of fruiting body powders, increase the contents of soluble polysaccharide (26.26-67.04 %) and uronic acid (16.97-31.12 %) and reduce the molecular weight of polysaccharides. The digestibility of fruiting body powder of H. erinaceus after semi-solid enzymolysis was increased by 31.4 %, compared with that of the fruiting body powder of H. erinaceus without enzymolysis. Semi-solid enzymolysis could enhance the protective effects of the fruiting body powders and polysaccharides on ethanol-induced human gastric mucosal epithelial cells (GES-1) cells, increase the production of superoxide dismutase (SOD, 0-37.33 %) and catalase (CAT, 2.47-18.46 %), and inhibit the production of malonaldehyde (MDA, 2.45-19.62 %), myeloperoxidase (MPO, 0-13.54 %), interleukin (IL-6, 4.39-24.62 %) and tumor necrosis factor-α (TNF-α, 5.97-12.25 %). Semi-solid enzymolysis could improve the inhibition rate of the fruiting body powder on gastric ulcer (32.70-46.26 %), inhibit oxidative stress and inflammation, and protect rats with acute gastric mucosal injury against the stimulation of ethanol on gastric mucosa. In conclusion, semi-solid enzymolysis may enhance the protective effects of the fruiting body powders and polysaccharides on gastric mucosal injury., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2023. Published by Elsevier B.V.)

Sambucus nigra (SN) berry extract is characterized by high antioxidant and anti-inflammatory activity. The current study aimed to investigate the effect of SN berry extract against indomethacin (IND)-induced gastric ulcer in rats and the mechanism involved. SN berry extract alleviated IND-induced gastric ulcers, as shown by assessing pathological manifestations in the gastric mucosa. These protective effects are attributed to attenuated oxidative damage to the gastric mucosa, correlated to increased activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), enhanced glutathione (GSH) levels, total antioxidant capacity (TAC), and upregulation of the Nrf2/HO-1 cascade. Moreover, oxidative stress markers, including malondialdehyde (MDA) and total oxidant status (TOS), were downregulated in SN-extract-treated animals. Furthermore, SN berry extract suppressed gastric mucosal inflammation by downregulating interleukin (IL)-33, IL-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) levels, and attenuating myeloperoxidase (MPO) activity. The protective effects of SN berry extract were similar to those exerted by esomeprazole (ESO), an acid-secretion-suppressive drug. In conclusion, SN berry extract has antiulcerative effects, alleviating oxidative stress and inflammation.

Alcoholic gastric ulcer is a common acute gastric injury disease. The drugs currently used in clinical practice not only cannot fundamentally treat gastric injury, but also have serious side effects. There is an urgent demand for the discovery of a mild drug to treat alcoholic gastric ulcers. Herein, the green carbon dots derived from charred Atractylodes macrocephala (CAM-CDs) were acquired and have been proven to be safe and effective in alleviating alcoholic gastric ulcers at an inhibition rate up to 60%. CAM-CDs can markedly attenuate the gastric mucosa damage such as mucosal defect, bleeding and inflammatory cell infiltration by histopathological examination. Serum and tissue inflammatory cytokine measurements, as well as immunohistochemistry results, indicate that its mechanism of gastric mucosal protection may involve the reduction of IL-1β and TNF-α by regulating inflammatory signaling pathway of the NF-κB/NLRP3 axis, as well as elevation of IL-10 levels. CAM-CDs also can reduce oxidative stress markers (MDA), increase PGE2 and mucin secretion (MUC5AC), and it simultaneously exerts slight inhibition of hydrogen potassium ATPase and pepsin activity to protect gastric mucosa, as well as increases the microbial diversity and regulates species composition of gut microbiota in rats with gastric ulcer. Our work provides a new perspective on utilizing carbon-based nanomaterials in the development of new mild drugs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The current study aimed at identifying the risk factors and initial diagnostic aids for abomasal ulcers. The risk factor analysis confirmed a significant association (P < 0.05) of abomasal ulcers with concentrate-rich diets (OR, 4.795; CI, 1.212-15.974) and concurrent disorders (OR, 2.978; CI, 0.987-8.980), while the buffaloes in early lactation (OR, 2.777; CI, 0.703-10.972) showed a higher tendency (P = 0.078) for the disorder. The depressed demeanour, dark or black manure (melena), anemia, tachycardia, decreased milk production, anorexia, tachypnea, absence of rumination, abdominal guarding, kyphosis, and tachypnea were the most frequent clinical signs. Subjecting the abomasal fluid for cultural isolation, gram staining, and stormy clot fermentation test identified the presence of clostridium perfringes, while screening through uniplex PCR detected cpa toxin. The buffaloes affected with type-3 and 4 abomasal ulcers exhibited a higher peritoneal fluid to serum ratio of total protein, albumin, and glucose with a low (P < 0.01) serum-ascites albumin gradient (SAAG) concentration compared to reference values of healthy buffaloes. The first two principal components of PCA explained 54.50% of the total variances with lymphocytes, creatine kinase, and rumen chloride levels as the top contributors to dimension I, and albumin, total protein, sodium, and methylene blue reduction time (MBRT) for rumen liquor as the major contributors to dimension II. The vector plot revealed lymphocytopenia, decreased hemoglobin, hypoalbuminemia, hypokalemia, decreased rumen pH, neutrophilia, eosinophilia, leucocytosis, greater MBRT, and higher rumen chloride, serum creatine kinase, and blood urea nitrogen as the major indicators for abomasal ulcers. Histopathological studies revealed infiltration of inflammatory cells in the mucosa along with multifocal areas of necrosis, degeneration, and eroded muscle structure. The study projected a few high-scored clinical signs and extremely variable clinical indicators as initial diagnostic aids of abomasal ulcers, which can be confirmed by ultrasonography and peritoneal fluid examination., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: To quantify phytochemicals using liquid chromatography and mass spectroscopy (LCMS) analysis and explore the therapeutic effect of Aesculus hippocastanum L. (AH) seeds ethanolic extract against gastric ulcers in rats., Methods: Preliminary phytochemical testing and LCMS analysis were performed according to standard methods. For treatment, the animals were divided into 7 groups including normal control, ulcer control, self-healing, AH seeds low and high doses, ranitidine and per se groups. Rats were orally administered with 10 mg/kg of indomethacin, excluding the normal control group (which received 1% carboxy methyl cellulose) and the per se group (received 200 mg/kg AH seeds extract). The test group rats were then given 2 doses of AH seeds extract (100 and 200 mg/kg, respectively), while the standard group was given ranitidine (50 mg/kg). On the 11th day, rats in all groups were sacrificed, and their stomach was isolated to calculate the ulcer index, and other parameters such as blood prostaglandin (PGE 2 ), tissue superoxide dismutase (SOD), catalase (CAT), malonyldialdehyde (MDA), and glutathione (GSH). All isolated stomach tissues were analyzed for histopathological findings., Results: The phytochemical examination shows that the AH seeds contain alkaloids, flavonoids, saponins, phenolic components, and glycosides. LCMS analysis confirms the presence of quercetin and rutin. The AH seeds extract showed significant improvement in gastric mucosa conditions after indomethacin-induced gastric lesions (P<0.01). Further marked improvement in blood PGE 2 and antioxidant enzymes, SOD, CAT, MDA and GSH, were observed compared with self-healing and untreated ulcer-induced groups (P<0.01). Histopathology results confirmed that AH seeds extract improved the mucosal layer and gastric epithelial membrane in treated groups compared to untreated ulcer-induced groups., Conclusions: LCMS report confirms the presence of quercetin and rutin in AH seeds ethanolic extract. The therapeutic effect of AH seeds extract against indomethacin-induced ulcer in rat model indicated the regenerated membrane integrity, with improved cellular functions and mucus thickness. Further, improved antioxidant enzyme level would help to reduce PGE 2 biosynthesis., (© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

The equine stomach consists of two separate non-glandular and glandular sections. Despite the incidence of most lesions in the non-glandular region, both stomach parts are prone to lesions. In this study, 41 hybrid-native horses, including 24 stallions and 17 mares, were examined over five years. In total, 27 horses (65.85%) that were sampled had lesions, including erosion, granuloma, or both on the glandular region of the stomach. Occurrence of gastric erosive and granulomatous lesions had no significant relationship with the age and gender of horses or the sampling season ( P >0.05). Moreover, parasites Gastrophilus and Habronema were mainly the primary cause of gastric erosive and granulomatous lesions respectively. In Periodic Acid Schiff (PAS) stained tissue sections, the inflammation severity in granulomatous lesions was higher and statistically significant, compared to erosive lesions ( P <0.05). Immunohistochemistry revealed negative expression of glial cell line-derived neurotrophic factor in gastric lesions, while its expression was relatively positive in normal stomachs. Interestingly, based on counting cells and evaluation of expression intensity, Chromogranin A expression in neuroendocrine glandular cells had a significant relationship with the increase of severity and depth of the lesions ( P <0.05). The results indicated that the glial cell line-derived neurotrophic factor does not affect the pathogenesis of equine gastric lesions while confirming the role of increment of gastric neuroendocrine cells in lesion progress. Furthermore, the increased expression of Ki67 and p53 proteins in granulomatous lesions, compared to other groups, may be associated with the proliferation and control process of the cells in measures regarding the formation and healing of the lesion., Competing Interests: The authors declare that they have no conflict of interest.

This study aimed to elucidate the gastro-protective effect of fucoidan against ethanol-induced gastric ulcer mediated via NLRP3-induced pyroptosis as an underlying mechanism, not yet assessed in prior research. Forty-eight male Albino mice were divided into six groups: Group I (normal control), group II (Ulcer/ethanol control), group III (Omeprazole + ethanol), group IV (fucoidan 25 mg + ethanol), group V (fucoidan 50 mg + ethanol) and group VI (fucoidan only). Fucoidan was administered orally for seven consecutive days followed by ulcer induction by a single oral dose of ethanol. Using colorimetric analysis, ELISA, qRT-PCR, histological assessment, and immunohistochemical studies, the results revealed that ethanol-induced ulcer exhibited an ulcer score of 42.5 ± 5.1 and a significant increase (p < 0.05) in malondialdehyde (MDA), nuclear factor kappa B (NF-κB), and interleukin 6 (IL-6) with a significant decrease in the gastro-protective mediators, prostaglandin E2 (PGE2), superoxide dismutase (SOD) and glutathione (GSH), accompanied with an increase in NLRP3, interleukin 1β (IL-1β), interleukin 18 (IL-18), caspase 1, caspase 11, gasdermin D, and toll-like receptor 4 (TLR4), compared with the normal control. Pre-treatment with fucoidan showed a comparable result with omeprazole. Additionally, pre-treatments elevated the levels of the gastro-protective mediators and lessened oxidative stress, relative to the positive control findings. Conclusively, fucoidan has a promising gastro-protective role by inhibiting inflammation and pyroptosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: In this study, we determined the gastroprotective and ulcer-healing effects of extracts (aqueous and methanolic) of Nauclea pobeguinii stem-back., Methods: Gastroprotective and healing activity were evaluated following a HCl/ethanol and an indomethacin-induced acute ulcers models; acetic acid, pylorus-ligature, pylorus ligature/histamine and pylorus ligature/acetylcholine-induced chronic ulcers models., Results: It emerges from this study that, at 100, 200 and 400 mg/kg, the extracts significantly reduced the various ulceration parameters. Compared to negative control male rats, the aqueous (100 mg/kg) and methanolic (400 mg/kg) extracts of Nauclea pobeguinii inhibited the ulcers induced by HCl/ethanol by 80.76 % and 100 % respectively, as well as ulcers induced by indomethacin by 88.28 % and 93.47 % respectively. Animals that received 200 mg/kg of both extracts showed a significant reduction in the levels of monocytes, lymphocytes, nitric oxide, MDA and a significant increase in the activities of SOD and catalase. Histological analysis showed repaired mucous epithelium at all doses of both extracts. Aqueous and methanol extracts inhibited ulceration indices by 89.33 % and 88.53 % for pylorus ligature, 83.81 % and 61.07 % for pylorus ligature/acetylcholine and 87.29 % and 99.63 % for pylorus ligature/histamine respectively. Both extracts protected the stomach lining with percentages inhibition of 79.49 % and 81.73 %, respectively in the ethanol test. The extracts induced a significant increase in mucus mass (p<0.001)., Conclusions: The aqueous and methanol extracts of Nauclea pobeguinii healed ulcers thanks to their anti-inflammatory, anti-oxidant, anti-secretory and cytoprotective properties., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Ethnopharmacological Relevance: Fridericia chica (Bonpl.) L.G. Lohmann (Bignoniaceae), is a climber native to Brazil, found in all Brazilian biomes. It is mostly known in Brazil as "carajiru," and home medicines made from the leaves have been used to cure disorders including stomach ulcers and other gastrointestinal disorders., Aim of the Study: The objective of the study was to investigate the F. chica hydroethanolic extract of leaves (HEFc) preventative and curative antiulcer gastrointestinal efficacy as well as the mechanisms of action using in vivo rodent models., Materials and Methods: F. chica was collected in the municipality of Juína, Mato Grosso, and its leaves were used to prepare the extract by maceration technique (70% hydroethanol in the 1:10 ratio, w/v) to obtain the HEFc. The chromatographic analysis of HEFc was carried out by High Performance Liquid Chromatography-Photo Diode Array-Electrospray Ionization-Mass Spectrometry (HPLC-PDA-ESI-MS)- LCQ Fleet™ system. To determine the potential antiulcer potential of HEFc (1, 5 and 20 mg/kg, p.o.), the gastroprotective activity was assessed in various animal models of stomach ulcers caused by acidified ethanol, water constraint stress, indomethacin, (acute), and acid acetic (chronic). Additionally, the prokinetic properties of the HEFC were assessed in mice. The gastroprotective underlying mechanisms were evaluated by the histopathological analysis and determination of gastric secretion (volume, free and total acidity), gastric barrier mucus, activation of PGs, NO, K  + ATP channels, α 2 -adrenoceptor, antioxidant activity (GSH, MPO and MDA), NO and mucosal cytokines (TNF-α, IL-1β, and IL-10) levels., Results: The chemical composition of HEFc was analyzed and apigenin, scutellarin, and carajurone were identified. HEFc (1, 5 and 20 mg/kg) showed effect against acute ulcers induced by HCl/EtOH with a reduction in the ulcerated area of 64.41% (p < 0.001), 54.23% (p < 0.01), 38.71% (p < 0.01), respectively. In the indomethacin experiment, there was no change in the doses tested, whereas in the water immersion restraint stress ulcer there was a reduction of lesions at doses of 1, 5, and 20 mg/kg by 80.34% (p < 0.001), 68.46% (p < 0.01) and 52.04% (p < 0.01). HEFc increased the mucus production at doses of 1 and 20 mg/kg in 28.14% (p < 0.05) and 38.36% (p < 0.01), respectively. In the pyloric ligation-induced model of gastric ulceration, the HEFc decreased the total acidity in all doses by 54.23%, 65.08%, and 44.40% (p < 0.05) and gastric secretory volume in 38.47% at dose of 1 mg/kg (p < 0,05) and increased the free acidity at the dose of 5 mg/kg by 11.86% (p < 0.05). The administration of EHFc (1 mg/kg) showed a gastroprotective effect possibly by stimulating the release of prostaglandins and activating K + ATP channels and α 2- adrenoreceptors. Also, the gastroprotective effect of HEFc involved an increase in CAT and GSH activities, and a reduction in MPO activity and MDA levels. In the chronic gastric ulcer model, the HEFc (1, 5 and 20 mg/kg) decreased the ulcerated area significantly (p < 0.001) at all doses by 71.37%, 91.00%, and 93.46%, respectively. In the histological analysis, HEFc promoted the healing of gastric lesions by stimulating the formation of granulation tissue and consequently epithelialization. On the other hand, regarding the effect of HEFc on gastric emptying and intestinal transit, it was observed that the extract did not alter gastric emptying, but there was an increase in intestinal transit at the dose of 1 mg/kg (p < 0.01)., Conclusion: These outcomes confirmed the advantages of Fridericia chica leaves for the treatment of stomach ulcers, which are well-known. HEFc was discovered to have antiulcer characteristics through multitarget pathways, which might be related to an increase in stomach defense mechanisms and a decrease in defensive factor. HEFc can be regarded as a potential new antiulcer herbal remedy because of its antiulcer properties, which may be attributed to the mixture of flavonoids, apigenin, scutellarin and carajurone., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Ginsenoside Rh4, a bioactive component extracted from Panax ginseng , exhibits various pharmacological activities, such as anti-inflammatory, anti-oxidation, anti-diabetes, anti-obesity, antitumor and immunity enhancement. However, the gastroprotective effect of ginsenoside Rh4 remains unknown. The present study evaluated the gastroprotective effect and potential mechanism of ginsenoside Rh4 in an ethanol-induced gastric ulcer model. Ginsenoside Rh4 (15, 30, and 60 mg kg -1 ) and omeprazole (30 mg kg -1 ) were administered orally for 7 days. The results showed that pretreatment with ginsenoside Rh4 reduced the gastric injury area and percentage of mucosal lesions in gastric tissue. Besides, treatment with ginsenoside Rh4 increased superoxide dismutase (SOD) activity, glutathione (GSH) and nitric oxide (NO) levels, reduced the content of malonaldehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), mediated the prostaglandin E-2-cyclooxygenase-2 (PGE2-Cox-2) pathway, and mitigated inflammation and oxidative stress via blockade of proinflammatory mitogen-activated protein kinase-nuclear factor κB (MAPK/NF-κB) signaling pathways. Furthermore, ginsenoside Rh4 significantly enhanced the protein expression of B-cell lymphoma gene 2 (Bcl-2), decreased the protein expression of Bcl-2-associated X protein (Bax) and tumor necrosis factor receptor superfamily member 6 (Fas), and inhibited the number of apoptotic cells in gastric tissues. The present work demonstrated that ginsenoside Rh4 exerted a considerable gastroprotective effect against ethanol-induced gastric ulcers in rats.