Tamarix aphylla derived metabolites ameliorate indomethacin-induced gastric ulcers in rats by modulating the MAPK signaling pathway, alleviating oxidative stress and inflammation: In vivo study supported by pharmacological network analysis.

Nature has proven to be a treasure resource of bioactive metabolites. In this regard, Tamarix aphylla (F. Tamaricaceae) leaves crude extract was investigated for its gastroprotective effect against indomethacin-induced damage to the gastric mucosa. Additionally, phytochemical investigation of the methanolic extract afforded eight flavonoids' derivatives (1-8). On pharmacology networking study, the isolated compounds identified 123 unique targets where only 45 targets were related to peptic ulcer conditions, these 45 targets include 11 targets specifically correlate to gastric ulcer. The protein-protein interaction defined the PTGS2 gene as one of the highly interacted genes and the complete pharmacology network defined the PTGS2 gene as the most represented gene. The top KEGG signaling pathways according to fold enrichment analysis was the EGFR tyrosine kinase inhibitor resistance pathway. As a result, these findings highlighted the significance of using T. aphylla leaves crude extract as an anti-gastric ulcer candidate, which provides a safer option to chemical antisecretory medicines, which are infamous for their negative side effects. Our findings have illuminated the potent anti-inflammatory and antioxidant effects of T. aphylla, which are likely mediated by suppressing IL-1ß, IL-6, TNF-α, and MAPK signaling pathways, without compromising gastric acidity.

Antidiabetic and antiulcer activity of methanolic extract of Tradescantia spathacea in rats.

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.

pH-responsive bioadhesive with robust and stable wet adhesion for gastric ulcer healing.

Development of bioadhesives that can be facilely delivered by endoscope and exhibit instant and robust adhesion with gastric tissues to promote gastric ulcer healing remains challenging. In this study, an advanced bioadhesive is prepared through free radical polymerization of ionized N-acryloyl phenylalanine (iAPA) and N-[tris (hydroxymethyl) methyl] acrylamide (THMA). The precursory polymer solution exhibits low viscosity with the capability for endoscope delivery, and the hydrophilic-hydrophobic transition of iAPA upon exposure to gastric acid can trigger gelation through phenyl groups assisted multiple hydrogen bonds formation and repel water molecules on tissue surface to establish favorable environment for interfacial interactions between THMA and functional groups on tissues. The in-situ formed hydrogel features excellent stability in acid environment (14 days) and exhibits firm wet adhesion to gastric tissue (33.4 kPa), which can efficiently protect the wound from the stimulation of gastric acid and pepsin. In vivo studies reveal that the bioadhesive can accelerate the healing of ulcers by inhibiting inflammation and promoting capillary formation in the acetic acid-induced gastric ulcer model in rats. Our work may provide an effective solution for the treatment of gastric ulcers clinically.

Multiple drug-delivery strategies to enhance the pharmacological and toxicological properties of Mefenamic acid.

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.

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

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

In vivo effects of a selected thiourea derivative 1-(2-chlorobenzoyl)-3-(2,3-dichlorophenyl) against nociception, inflammation and gastric ulcerogenicity: Biochemical, histopathological and in silico approaches.

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.

The Anti-ulcer Potential of Weissella cibaria Assisted Bio-fermented Product of Citrus limetta Waste Peel in Wistar Albino Rats.

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.

Syringic acid guards against indomethacin-induced gastric ulcer by alleviating inflammation, oxidative stress and apoptosis.

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-ß (TGF-ß), expressions of COX and prostaglandin E2, 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.

Physiological healing of chronic gastric ulcer is not impaired by the hydrogen sulphide (H2S)-releasing derivative of acetylsalicylic acid (ATB-340): functional and proteomic approaches.

Gastric ulcers affect approx. 10% of population. Non-steroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid (ASA) predispose to or impair the physiologically complex healing of pre-existing ulcers. Since H2S is an endogenous cytoprotective molecule, we hypothesized that new H2S-releasing ASA-derivative (ATB-340) could overcome pathological impact of NSAIDs on GI regeneration.Clinically translational gastric ulcers were induced in Wistar rats using state-of-the-art microsurgical model employing serosal application of acetic acid. This was followed by 9 days long i.g. daily treatment with vehicle, ATB-340 (6-24 mg/kg) or equimolar ASA doses (4-14 mg/kg). Ulcer area was assessed macro- and microscopically. Prostaglandin (PG)E2  levels, indicating pharmacological activity of NSAIDs and 8-hydroxyguanozine content, reflecting nucleic acids oxidation in serum/gastric mucosa, were determined by ELISA. Qualitative and/or quantitative pathway-specific alterations at the ulcer margin were evaluated using real-time PCR and mass spectrometry-based proteomics.ASA, unlike ATB-340, dose-dependently delayed/impaired gastric tissue recovery, deregulating 310 proteins at the ulcer margin, including Ras signalling, wound healing or apoptosis regulators. ATB-340 maintained NSAIDs-specific cyclooxygenase-inhibiting capacity on systemic and GI level but in time-dependent manner. High dose of ATB-340 (24 mg/kg daily), but not ASA, decreased nucleic acids oxidation and upregulated anti-oxidative/anti-inflammatory heme oxygenase-1, 24-dehydrocholesterol reductase or suppressor of cytokine signalling (SOCS3) at the ulcer margin.Thus, ASA impairs the physiological healing of pre-existing gastric ulcers, inducing the extensive molecularly functional and proteomic alterations at the wound margin. H2S-releasing ATB-340 maintains the target activity of NSAIDs with limited impact on gastric PGE2 signalling and physiological GI regeneration, enhancing anti-inflammatory and anti-oxidative response, and providing the pharmacological advantage.

Construction of diallyltrisulfide nanoparticles for alleviation of ethanol-induced acute gastric injury.

Gastric ulcer, a significant health issue characterized by the degradation of the gastric mucosa, often arises from excessive gastric acid secretion and poses a challenge in current medical treatments due to the limited efficacy and side effects of first-line drugs. Addressing this, our study develops a novel therapeutic strategy leveraging gas therapy, specifically targeting the release of hydrogen sulfide (H2S) in the treatment of gastric ulcers. We successfully developed a composite nanoparticle, named BSA·SH-DATS, through a two-step process. Initially, bovine serum albumin (BSA) was sulfhydrated to generate BSA·SH nanoparticles via a mercaptosylation method. Subsequently, these nanoparticles were further functionalized by incorporating diallyltrisulfide (DATS) through a precise Michael addition reaction. This sequential modification resulted in the creation of BSA·SH-DATS nanoparticles. Our comprehensive in vitro and in vivo investigations demonstrate that these nanoparticles possess an exceptional ability for site-specific action on gastric mucosal cells under the controlled release of H2S in response to endogenous glutathione (GSH), markedly diminishing the production of pro-inflammatory cytokines, thereby alleviating inflammation and apoptosis. Moreover, the BSA·SH-DATS nanoparticles effectively regulate critical inflammatory proteins, including NF-κB and Caspase-3. Our study underscores their potential as a transformative approach for gastric ulcer treatment.

Ferulic acid nanoemulsion as a promising anti-ulcer tool: in vitro and in vivo assessment.

OBJECTIVE: Ferulic acid (FA) is a promising nutraceutical molecule which exhibits antioxidant and anti-inflammatory properties, but it suffers from poor solubility and bioavailability. In the presented study, FA nanoemulsions were prepared to potentiate the therapeutic efficacy of FA in prevention of gastric ulcer. METHODS: FA nanoemulsions were prepared, pharmaceutically characterized, and the selected nanoemusion was tested for its ulcer-ameliorative properties in rats after induction of gastric ulcer using ethanol, by examination of stomach tissues, assessment of serum IL-1ß and TNF-α, assessment of nitric oxide, prostaglandin E2, glutathione, catalase and thiobarbituric acid reactive substance in stomach homogenates, as well as histological and immunohistochemical evaluation. RESULTS: Results revealed that the selected FA nanoemulsion showed a particle size of 90.43 nm, sustained release of FA for 8 h, and better in vitro anti-inflammatory properties than FA. Moreover, FA nanoemulsion exhibited significantly better anti-inflammatory and antioxidant properties in vivo, and the gastric tissue treated with FA nanoemulsion was comparable to the normal control upon histological and immunohistochemical evaluation. CONCLUSION: Findings suggest that the prepared ferulic acid nanoemulsion is an ideal anti-ulcer system, which is worthy of further investigations.

Construction of Magnolol Nanoparticles for Alleviation of Ethanol-Induced Acute Gastric Injury.

Ethanol (EtOH) has been identified as a potential pathogenic factor in gastric ulcer development primarily due to its association with gastric injury and excessive production of reactive oxygen species. Magnolol (Mag), the principal active compound in Magnolia officinalis extract, is well studied for its notable anti-inflammatory and antioxidant properties. However, its limited solubility, propensity for agglomeration, and low absorption and utilization rates significantly restrict its therapeutic use. This study aims to overcome these challenges by developing a Mag nanoparticle system targeting the treatment and prevention of EtOH-induced gastric ulcers in mice. Utilizing a click chemistry approach, we successfully synthesized this system by reacting thiolated bovine serum albumin (BSA·SH) with Mag. The in vitro analysis revealed effective uptake of the BSA·SH-Mag nanoparticle system by human gastric epithelial cells (GES-1), showcasing its antioxidant and anti-inflammatory capabilities. Additionally, BSA·SH-Mag exhibited gradual disintegration and release in simulated gastric fluid, resulting in a notable reduction of oxidative stress in gastric tissues and mucosal tissue repair and effectively reducing inflammatory expression. Furthermore, BSA·SH-Mag attenuated EtOH-induced gastric inflammation by decreasing the level of NOX4 protein expression and augmenting the level of Nrf2 protein expression. In conclusion, our findings indicate that BSA·SH-Mag represents a promising candidate as an oral therapeutic for gastric ulcer treatment.

Comparison of vonoprazan and proton pump inhibitors for the treatment of gastric endoscopic submucosal dissection-induced ulcer: an updated systematic review and meta-analysis.

BACKGROUND: Both vonoprazan and proton pump inhibitors (PPIs) are currently used to treat artificial ulcers after gastric endoscopic submucosal dissection. However, evidence-based medicine proving the efficacy of vonoprazan is still lacking. Therefore, this meta-analysis aimed to compare the efficacy of vonoprazan and PPIs for the treatment of artificial ulcers after gastric endoscopic submucosal dissection. METHODS: The PubMed, EMBASE and Cochrane Library databases were searched up to September 2023 for related randomized controlled trials (RCTs). RCTs that compared the efficacy of vonoprazan and PPIs in treating artificial gastric ulcers after gastric endoscopic submucosal dissection were included. Two independent reviewers screened the included studies, extracted the data and assessed the risk of bias. The following outcomes were extracted for comparison: ulcer healing rate, ulcer shrinkage rate, delayed postoperative bleeding rate, and ulcer perforation rate. RESULTS: Nine randomized controlled trials involving 926 patients were included. The pooled results showed that vonoprazan had a significantly lower rate of delayed postoperative bleeding than did PPIs (RR = 0.46; 95% CI = 0.23-0.91; P = 0.03). No significant differences were found in terms of ulcer healing, shrinkage rates, or ulcer perforation rates between vonoprazan and PPIs. CONCLUSIONS: Compared with PPIs, vonoprazan is superior at reducing delayed postoperative bleeding after endoscopic submucosal dissection. However, further studies are needed to prove the efficacy of vonoprazan. SYSTEMATIC REVIEW REGISTRATION: Identifier CRD42024509227.

Molecular docking, characterization, ADME/toxicity prediction, and anti-ulcer activity of new quercetin derivatives on indomethacin-induced gastric ulcer in mice.

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.

Argel's stemmoside C as a novel natural remedy for mice with alcohol-induced gastric ulcer based on its molecular mechanistic pathways.

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-1ß, & 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.

The protective effects of Gamma-linolenic acid against indomethacin-induced gastric ulcer in rats.

The primary goal of the investigation was to analyse the anti-inflammatory and antioxidant properties of Gamma-linolenic acid (GLA) on rats with indomethacin (IND)-induced gastric ulcers. Thirty rats were divided into five groups: Control, IND (50 mg/kg, p.o.), IND pretreated with GLA 100 mg/kg (p.o. for 14 d), IND pretreated with GLA 150 mg/kg (p.o. for 14 d) and IND pretreated with omeprazole (20 mg/kg, p.o. for 14 d). The stomach tissues were examined to calculate the ulcer index and pH and analyse biochemical markers (prostaglandin E2 (PGE2), cyclooxygenase 1 (COX1), TNF-1, IL-6 and intercellular adhesion molecule-1 (ICAM1)) and oxidative stress parameters (malondialdehyde: (MDA), superoxide dismutase (SOD), glutathione (GSH) and CAT (catalase)) as well as undergo histopathological assessment. GLA 100 and 150 mg/kg showed a protective effect against IND-induced gastric damage. It reduced levels of COX1, TNF-1, IL-6 and ICAM and increased PGE2 levels. GLA also normalised antioxidant function by modulating MDA, SOD, GSH and CAT. GLA intervention protects against IND-induced gastric ulcers by restoring oxidant/antioxidant balance and reducing inflammation.

Fish oil ameliorates ethanol-induced gastric injury in rat by modulating gene related to apoptosis.

Gastric ulcers are a type of digestive disease that can severely affect a person's quality of life. Our study aimed to investigate the effects of fish oil on ethanol-induced gastric ulcers in rats, with the purpose of providing more comprehensive information on the topic. The study looked at various factors such as gastric ulcer index, and nitric oxide (NO) levels in stomach tissue. To investigate apoptosis, the mRNA levels of Bax, Bcl-2, and Caspase 3 were analyzed. The results showed that fish oil can reduce gastric acidity and the gastric ulcer index in cases of ethanol-induced gastric ulcers. It was found that fish oil can increase NO levels and improve the anti-apoptotic system by increasing the expression of Bcl-2 while decreasing the expression of Bax and Caspase 3. In general, the study demonstrates that fish oil can protect the stomach from ethanol-induced damage by reducing the apoptosis pathway via nitric oxide.

Banxia Xiexin decoction promotes gastric lymphatic pumping by regulating lymphatic smooth muscle cell contraction and energy metabolism in a stress-induced gastric ulceration rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine (TCM) formula Banxia Xiexin decoction (BXD) has definite therapeutic effect in treating stress-induced gastric ulceration (SIGU) and many other gastrointestinal diseases, but its effect on gastric lymphatic pumping (GLP) remains unclear. AIM OF THE STUDY: Elucidating the role of GLP in SIGU and BXD treatment, and exploring the molecular mechanisms of GLP regulation. MATERIALS AND METHODS: In vivo GLP imaging were performed on SIGU rat model, and the lymphatic dynamic parameters were evaluated. Gastric antrum tissues and serum were collected for macroscopic, histopathological and ulcerative parameters analysis. Gastric lymphatic vessel (GLV) tissues were collected for RNA-Seq assays. Differentially expressed genes (DEGs) were screened from RNA-Seq result and submitted for transcriptomic analysis. Key DEGs and their derivative proteins were measured by qRT-PCR and WB. RESULTS: GLP was significantly suppressed in SIGU rats. BXD could recover GLP, ameliorate stomach lymphostasis, and alleviate the ulcerative damage. Transcriptome analysis of GLV showed the top up-DEGs were concentrated in smooth muscle contraction signaling pathway, while the top the down-DEGs were concentrated in energy metabolism pathways especially fatty acid degradation pathway, which indicated BXD can promote lymphatic smooth muscle contraction, regulate energy metabolism, and reduce fatty acid degradation. The most possible target of these mechanisms was the lymphatic smooth muscle cells (LSMCs) which drove the GLP. This speculation was further validated by the qRT-PCR and WB assessments for the level of key genes and proteins. CONCLUSIONS: By activating the smooth muscle contraction signaling pathway, restoring energy supply, modulating energy metabolism program and reducing fatty acid degradation, BXD effectively recovered GLP, mitigated the accumulation of inflammatory cytokines and metabolic wastes in the stomach, which importantly contributes to its efficacy in treating SIGU.

Aloe vera gel confers therapeutic effect by reducing pyroptosis in ethanol-induced gastric ulcer rat model: Role of NLRP3/GSDMD signaling pathway.

BACKGROUND: Gastric ulcer (GU) is a common gastrointestinal tract illness. Aloe vera has anti-inflammatory, antioxidant, and healing characteristics. This research sought to explore the therapeutic impact of Aloe vera gel on ethanol-provoked GU in rats and to elucidate the underlying mechanisms involved. METHODS: An ethanol-induced GU rat model was constructed using forty male Wistar rats distributed at random into four groups: control, ulcer, pantoprazole, and Aloe vera. Gross evaluation of the stomach, ulcer index (UI), inhibition index, and gastric pH estimation were analyzed. Gastric malondialdehyde (MDA) and reduced glutathione (GSH) were determined using the spectrophotometric method, and serum gastrin level was measured by an enzyme-linked immunosorbent assay. Gastric nucleotide-binding domain, leucine-rich repeat, and pyrin domain PYD containing protein 3 (NLRP3) and gasdermin D (GSDMD) mRNA expression levels were estimated by quantitative real-time PCR. Finally, the histopathological examination of the glandular part of stomach tissue was done. RESULTS: The ulcer group revealed a significant increase in MDA, gastrin, NLRP3, and GSDMD and a decrease in gastric pH and GSH compared to the control group. Gross investigations of the ulcer group revealed a hemorrhagic lesion in the stomach and an increase in UI. Also, histopathological results for this group showed severe epithelial loss, haemorrhage, inflammatory cell infiltration, and blood vessel congestion. However, Aloe vera treatment improved the gross, biochemical, molecular, and histopathological alterations induced by ethanol when compared to the ulcer group. CONCLUSIONS: Aloe vera exerted antiulcer activities through modulation of oxidant/antioxidant status, anti-secretory properties, and mitigation of pyroptosis.

Clinical Impact of Proton Pump Inhibitor and Potassium-Competitive Acid Blocker for Predicting the Curability of Endoscopic Resection in Ulcerative Early Gastric Cancer.

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.