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.

Omeprazole taken once every other day can effectively prevent aspirin-induced gastrointestinal mucosal damage in rats.

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.

Duloxetine protected indomethacin-induced gastric mucosal injury by increasing serotonin-dependent RANTES expression and activating PI3K-AKT-VEGF pathway.

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.

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.

Probiotic bacteria protect against indomethacin-induced gastric ulcers through modulation of oxidative stress, inflammation, and apoptosis.

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.

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.

Protective effect of Enterococcus faecium against ethanol-induced gastric injury via extracellular vesicles.

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.

Ipomoea carnea mitigates ethanol-induced ulcers in irradiated rats via Nrf2/HO-1 pathway: an in vivo and in silico study.

The aim of this study was to investigate the potential of Ipomoea carnea flower methanolic extract (ICME) as a natural gastroprotective therapy against ethanol-induced gastric ulcers, particularly in individuals exposed to ionizing radiation (IR). The study focused on the Nrf2/HO-1 signaling pathway, which plays a crucial role in protecting the gastrointestinal mucosa from oxidative stress and inflammation. Male Wistar rats were divided into nine groups, the control group received distilled water orally for one week, while other groups were treated with ethanol to induce stomach ulcers, IR exposure, omeprazole, and different doses of ICME in combination with ethanol and/or IR. The study conducted comprehensive analyses, including LC-HRESI-MS/MS, to characterize the phenolic contents of ICME. Additionally, the Nrf2/HO-1 pathway, oxidative stress parameters, gastric pH, and histopathological changes were examined. The results showed that rats treated with IR and/or ethanol exhibited histopathological alterations, increased lipid peroxidation, decreased antioxidant enzyme activity, and reduced expression levels of Nrf2 and HO-1. However, pretreatment with ICME significantly improved these parameters. Phytochemical analysis identified 39 compounds in ICME, with flavonoids, hydroxybenzoic acids, and fatty acids as the predominant compounds. Virtual screening and molecular dynamics simulations suggested that ICME may protect against gastric ulceration by inhibiting oxidative stress and inflammatory mediators. In conclusion, this study demonstrates the potential of ICME as a natural gastroprotective therapy for preventing gastric ulcers. These findings contribute to the development of novel interventions for gastrointestinal disorders using natural plant extracts particularly in individuals with a history of radiation exposure.

Protective effects of an alcoholic extract of Kaempferia galanga L. rhizome on ethanol-induced gastric ulcer in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The rhizome of Kaempferia galanga L., a medicinal and edible Plant, was widely distributed in many Asian and African counties. It has been traditionally used to treat gastroenteritis, hypertension, rheumatism and asthma. However, there is a lack of modern pharmacology studies regarding its anti-gastric ulcer activity. AIM OF THE STUDY: The objective of this study is to investigate the protective effects of an extract from K. galanga L. rhizome (Kge) and its active components kaempferol and luteolin on ethanol-induced gastric ulcer. MATERIALS AND METHODS: The kge was prepared by ultrasonic-assisted extraction, and the contents of kaempferol and luteolin were determined by HPLC. The mice were randomly divided into seven groups: blank control (0.5 % CMC-Na; 0.1 mL/10 g), untreatment (0.5 % CMC-Na; 0.1 mL/10 g), Kge (100, 200 and 400 mg/kg), kaempferol (100 mg/kg) and luteolin (100 mg/kg) groups. The mice were treated intragastrically once daily for 7 days. At 1 h post the last administration, the mice in all groups except the blank control group were intragastrically administrated with anhydrous alcohol (0.1 mL/10 g) once to induce gastric ulcer. Then, fasting was continued for 1 h, followed by sample collection for evaluation by enzyme-linked immunosorbent assay and real-time reverse transcription polymerase chain reaction assay. RESULTS: The contents of kaempferol and luteolin in Kge were determined as 3713 µg/g and 2510 µg/g, respectively. Alcohol induced severely damages with edema, inflammatory cell infiltration and bleeding, and the ulcer index was 17.63 %. After pre-treatment with Kge (100, 200 and 400 mg/kg), kaempferol and luteolin, the pathological lesions were obviously alleviated and ulcer indices were reduced to 13.42 %, 11.65 %, 6.54 %, 3.58 % and 3.85 %, respectively. In untreated group, the contents of Ca2+, myeloperoxidase, malondialdehyde, NO, cyclic adenosine monophosphate and histamine were significantly increased, while the contents of hexosamine, superoxide dismutase, glutathione peroxidase, and prostaglandin E2 were significantly decreased; the transcriptional levels of IL-1α, IL-1ß, IL-6, calcitonin gene related peptide, substance P, M3 muscarinic acetylcholine receptor, histamine H2 receptor, cholecystokinin 2 receptor and H+/K+ ATPase were significantly increased when compared with the blank control group. After pre-treatment, all of these changes were alleviated, even returned to normal levels. Kge exhibited anti-gastric ulcer activity and the high dose of Kge (400 mg/kg) exhibited comparable activity to that of kaempferol and luteolin. CONCLUSION: The study showed that K. galanga L., kaempferol, and luteolin have protective effects against ethanol-induced gastric ulcers. This is achieved by regulating the mucosal barrier, oxidative stress, and gastric regulatory mediators, as well as inhibiting the TRPV1 signaling pathway and gastric acid secretion, ultimately reducing the gastric ulcer index.

Effects of the protective and therapeutic effect of yogurt enriched with Citrus sinensis essential oil against ibuprofen-induced gastric ulcer in elderly rats.

The aim of this study was to evaluate the effect of Citrus sinensis essential oil (EO) on the proximate composition of yogurt over a 28-day shelf life and to investigate the therapeutic and prophylactic effects of functional yogurt on ibuprofen-induced gastric ulcers in a rat model. It was observed that the yogurt group containing C. sinensis EO had higher acidity, total solids, and ash values. Histologic evaluation of the stomachs of rats with gastric ulcers revealed that rats fed with functional yogurt had fewer lesions compared to the control group. The treatment group had fewer lesions than the positive control (p > 0.05). Lesions in the glandular mucosa of the prophylactic group were significantly lower than those in the positive control group (p < 0.05). Yogurt with C. sinensis EO may be beneficial in reducing the severity of ulcers and improving overall health.

Anti H. pylori, anti-secretory and gastroprotective effects of Thymus vulgaris on ethanol-induced gastric ulcer in Sprague Dawley rats.

The objectives of the present study were to evaluate the acute toxicity, gastroprotective, therapeutic, anti-inflammatory and anti H. pylori activities of T. vulgaris total plant extract against ethanol-induced gastric ulcers in Sprague Dawley rats. Animals were divided into five groups i.e G-1 (Normal Control), Group 2 (ulcer control) were administered orally with 0.5% Carboxymethylcellulose (CMC), Group 3 (omeprazole treated) was administered orally with 20 mg/kg of omeprazole and Groups 4 and 5 (Low dose and High dose of the extract) were administered orally with 250, and 500 mg/ kg of Thymus vulgaris extract, respectively. After 1 hour, the normal group was orally administered with 0.5% CMC (5 ml/kg), whereas absolute alcohol (5ml/ kg) was orally administered to the ulcer control group, omeprazole group, and experimental groups. Stomachs were examined macroscopically and microscopically. Grossly, rats pre-treated with T. vulgaris demonstrated significantly decreased ulcer area and an increase in mucus secretion and pH of gastric content compared with the ulcer control group. Microscopy of gastric mucosa in the ulcer control group showed severe damage to gastric mucosa with edema and leukocytes infiltration of the submucosal layer. However, rats pretreated with omeprazole or Thyme vulgaris exhibited a mild to moderate disruption of the surface epithelium and lower level of edema and leukocyte infiltration of the submucosal layer. The T. vulgaris extract caused up-regulation of Hsp70 protein, down-regulation of Bax protein, and intense periodic acid Schiff uptake of the glandular portion of the stomach. Gastric mucosal homogenate of rats pre-treated with T. vulgaris exhibited significantly increased superoxide dismutase (SOD) and catalase (CAT) activities while malondialdehyde (MDA) level was significantly decreased. Based on the results showed in this study, Thymus vulgaris extract can be proposed as the safe medicinal plants for use and it has considerable gastroprotective potential via stomach epithelium protection against gastric ulcers and stomach lesions.

Pylorus ligation-induced hyperacidity: synergistic prophylactic effects of linagliptin and L-arginine via up-regulation of EP4 receptor subtype and improvement of vascular endothelial damage.

Gastric hyperacidity and ulceration are chronic diseases characterized by repeated healing followed by re-exacerbation. The study aims to protect against gastric hyperacidity without interfering with gastric acid secretion. Pylorus ligation-induced hyperacidity is commonly utilized in the induction of gastric ulcers.Forty-two rats were distributed into seven groups (n = 6). Group I comprised sham-operated group. Group II served as pylorus-ligation group. Groups III-VII were given oral Linagliptin (LN; 3 and 6 mg/kg), L-arginine (LA; 150 and 300 mg/kg) and their combination (LN 3 + LA 150 mg/kg), respectively for 7 days. On the 8th day, groups II-VII were subjected to pylorus-ligation.Treatment of pylorus-ligated rats with LN, LA and their combination improved the gastric hyperacidity as exhibited by a marked reduction in the gastric juice volume, total and free acidities and pepsin contents with a noticeable increase in pH. Pre-treatment with LN, LA and their combination showed a marked alleviation in the gastric inflammatory indicators evidenced by reduction in the gastric levels of MCP-1and Il-1ß as well as elevation of eNOS levels versus the sham-operated group. A marked up-regulation in the gastric gene expression of PGE, EP4 and VEGF accompanied by an improvement of the histopathologic pictures/scores, and TNF-α and caspase-3 immuno-staining were also recorded.By estimating the combination-index, it can be concluded that combining LN with LA exhibited prophylactic synergistic effects in ameliorating pylorus ligated-induced hyperacidity, mainly via up-regulation of EP4 receptor and improvement of vascular endothelial damage through VEGF expression in gastric mucosa.

Boric Acid Alleviates Gastric Ulcer by Regulating Oxidative Stress and Inflammation-Related Multiple Signaling Pathways.

Oxidative stress and inflammation have pivotal roles in gastric ulcer development caused by alcohol consumption. Trace element boric acid taken into the human and animal body from dietary sources displays strong antioxidant and anti-inflammatory functions. However, the mechanisms underlying these actions of boric acid remain unclear, and its effectiveness in preventing gastric lesions is unknown. Therefore, the present study was undertaken to evaluate the protective effects of boric acid in alcohol-induced gastric ulcer and elucidate its potential mechanisms. Gastric ulcer was induced by 75% oral ethanol administration in rats, and the effectiveness of prophylactic boric acid treatment at 100 mg/kg concentration was assessed by histopathological examination, ELISA assay and qRT-PCR. Gross macroscopic and histopathological evaluations revealed that boric acid alleviated gastric mucosal lesions. Boric acid decreased reactive oxygen species (ROS) and malondialdehyde (MDA) concentration and the overall oxidation state of the body while improving antioxidant status. It reduced the concentration of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). The mRNA expression of JAK2 and STAT3 was decreased while the expression of AMPK was increased with boric acid pretreatment. Moreover, Sema3A and PlexinA1 levels were elevated upon boric acid pretreatment, and homocysteine levels were reduced. Our results demonstrated that boric acid protects gastric mucosa from ethanol-induced damage by regulating oxidative and inflammatory responses. In addition, our findings suggested that the gastroprotective activity of boric acid could be attributed to its regulatory function in the IL-6/JAK2/STAT3 signaling modulated by AMPK and that Sema3A/PlxnA1 axis and homocysteine are potentially involved in this process.

Antioxidant potentialities and gastroprotective effect of Reichardia picroides extracts on Ethanol/HCl induced gastric ulcer rats.

The goal of this study was to determine for the first time the polyphenol content, antioxidant, and gastroprotective properties of the roots and leaves of Reichardia picroides. TPC considerably varied as a function of organs and solvent nature and ranged from 50 to 284.80 mg GAE/g DW. Leaves exhibited the highest amount of phenolics by using acetone 70%, the same tendency was observed for antioxidant activity. Besides, in vivo gastro-protective effects following HCl/EtOH-induced ulcer models displayed that roots extract at a high dose (500 mg) seemed to be the best performing extract with a decrease of ulceration index (UI) and an increase in the percentage of protection (PP), SOD, CAT, and GPX activities. All these data have been proved with principal component analysis (PCA). Overall, the results indicated that R. picroides could be considered a valuable source of natural compounds, which are beneficial for human health.

Clinical effects of a combination of phenylbutazone and omeprazole on chronic lameness in Mongolian horses.

BACKGROUND: Phenylbutazone (PBZ) is the most commonly used drug to treat symptoms of lameness in horses; however, it is associated with adverse effects such as gastric ulcer syndrome (EGUS). Interestingly, many practitioners prescribe omeprazole (OME) concurrently with PBZ to prevent the development of EGUS. However, the efficacy and safety of this practice in Mongolian horses with chronic lameness remain unknown. OBJECTIVES: To evaluate the clinical effects of a combination of PBZ and OME on chronic lameness in Mongolian horses. STUDY DESIGN: Randomised block experimental design. METHODS: Eighteen Mongolian horses with lameness score was ≥3 points, were divided into three treatment groups, with six horses in each group: placebo (CON), PBZ (4.4 mg/kg PO q. 24 h), or PBZ plus OME (4 mg/kg PO q. 24 h; PBZ + OME) in a randomised block design based on the initial lameness score. The horses were treated for 15 days. During this period, weekly gastroscopy, and physiological and biochemical tests were performed. RESULTS: Both PBZ (median 1.0, interquartile range [IQR]: 0.8-1.3; p = 0.01) and PBZ + OME (median 1.0, IQR: 1.0-1.0; p = 0.01) significantly decreased the lameness score compared with before administration. In addition, PBZ significantly increased the equine glandular gastric disease (EGGD) score (3.0 ± 0.6, p < 0.001), GT-17 content (293.4 ± 21.8 pg/mL, p < 0.001), and pepsinogen-1 (PG1) content (295.3 ± 38.3 ng/mL, p < 0.001) compared with CON or PBZ + OME. However, it significantly reduced the total protein (53.6 ± 1.5 g/L, p < 0.05) and albumin (25.5 ± 1.8 g/L, p < 0.05) contents. Nevertheless, compared with PBZ, PBZ + OME significantly decreased the EGGD score (0.3 ± 0.5, p < 0.001) and significantly increased the gastric fluid pH (7.3 ± 0.5, p < 0.001), total protein content (62.5 ± 4.6 g/L, p = 0.009), and albumin content (29.4 ± 1.1 g/L, p = 0.004). Meanwhile, they significantly diminished the gastrin 17 (GT-17) (162.0 ± 21.0 pg/mL, p < 0.001) and PG1 (182.4 ± 22.5 ng/mL, p < 0.001) contents. MAIN LIMITATIONS: Individual differences in horses were larger, but the sample size was small. There was larger interval between observations for each index. CONCLUSIONS: Compared with PBZ alone, PBZ + OME had no therapeutic effect on chronic lameness; however, it reduced the occurrence of EGGD in Mongolian horses. Horses may be protected against chronic lameness and PBZ-induced EGGD by increasing the pH value, decreasing serum PG1 and GT-17 content, and preventing the reduction of myeloperoxidase content.

Aqueous extract of the bark of Uncaria tomentosa, an amazonian medicinal plant, promotes gastroprotection and accelerates gastric healing in rats.

ETHNOPHARMACOLOGICAL IMPORTANCE: Uncaria tomentosa Willd. DC., is used in the Amazonian region of South America, wherein ethnic groups use the plant to treat diseases, including gastric disorders. However, despite its widespread popular use, this species has yet to be assessed for its anti-ulcer effects. AIM OF THE STUDY: In this study, we aimed to evaluate the in vivo gastroprotective and gastric healing activities of an aqueous extract of the bark of Uncaria tomentosa (AEUt) and sought to gain an understanding of the pharmacological mechanisms underlying these biological effects. MATERIALS AND METHODS: To verify the gastroprotective properties rats were treated with AEUt (30, 60, or 120 mg/kg) prior to inducing gastric ulceration with ethanol or piroxicam. Additionally, the involvement of nitric oxide, non-protein sulfhydryl compounds (NP-SH), α-2 adrenergic receptors, and prostaglandins was investigated. Furthermore, a pylorus ligature model was employed to investigate the antisecretory activity of AEUt. The gastric healing effects of AEUt (60 mg/kg) were examined in rats in which ulceration had been induced with 80% acetic acid, whereas the quality of healing was evaluated in mice with interleukin-induced recurrent ulcers. We also evaluated the in vivo thickness of the gastric wall using ultrasonography. Moreover, the levels of reduced glutathione (GSH) and malondialdehyde (MDA) were evaluated in ulcerated mucosa, and we determined the activities of the enzymes myeloperoxidase (MPO), N-acetyl-ß-D-glycosaminidase, superoxide dismutase, catalase, and glutathione S-transferase. In addition, we assessed the effects of AEUt on cell viability and subjected the AEUt to phytochemical analyses. RESULTS: Administration of the AEUt (60 or 120 mg/kg) prevented ethanol- and piroxicam-induced ulceration, which was also confirmed histologically. Moreover, we observed that pre-treatment with NEM and indomethacin abolished the gastroprotective effects of AEUt, thereby indicating the involvement of NP-SH and prostaglandins in these protective effects. In addition, we found that the administration of AEUt had no appreciable effects on the volume, acidity, or peptic activity of gastric juice. Furthermore, the AEUt (60 mg/kg) accelerated the gastric healing of acetic acid-induced ulcers by 46.2% and ultrasonographic findings revealed a reduction in the gastric wall thickness in this group. The gastric healing effect of AEUt was also accompanied by a reduction in MPO activity. The AEUt (60 mg/kg) also minimized ulcer recurrence in mice exposed to IL-1ß and was associated with the maintenance of GSH levels and a reduction in MDA contents. We deduce that the biological effects of AEUt could be associated with the activities of polyphenols and the alkaloids isomitraphylline and mitraphylline, identified as predominant constituents of the AEUt. Furthermore, we found no evidence to indicate that AEUt would have any cytotoxic effects. CONCLUSION: Collectively, our findings provide compelling evidence indicating the therapeutic efficacy of U. tomentosa. Our data indicate that compounds in AEUt confer gastroprotection and that this preventive effect of AEUt was accompanied by gastric healing and a reduction in gastric ulcer recurrence. Moreover, we provide evidence to indicate that the gastroprotective and gastric healing effects involve the antioxidant system and anti-inflammatory responses that contribute to preserving the gastric mucosa.

Caffeic acid phenethyl ester attenuates indomethacin-induced gastric ulcer in rats.

Gastric ulcer is one of the most frequent gastrointestinal ailments worldwide. Indomethacin, one of the most potent NSAIDs, suffers undesirable ulcerogenic activity. Caffeic acid phenethyl ester (CAPE) has known health benefits. The current study examined the potential of CAPE to combat indomethacin-induced gastric ulcers in rats. Animals were randomized into 5 groups: control, Indomethacin (50 mg/kg) mg/kg), Indomethacin + CAPE (5 mg/kg/day), Indomethacin + CAPE (10 mg/kg), and Indomethacin + Omeprazole (30 mg/kg). CAPE prevented the rise in ulcer index, attenuated histopathological changes and preserved gastric mucin concentration. CAPE efficiently significantly prevented accumulation of malondialdehude (MDA) and prevented exhaustion of the enzymatic activities of catalase (CAT) and superoxide dismutase (SOD). Further, CAPE prevented the rise in the expression of tumor necrosis factor-α (TNF-α), cyclo-oxygenase-2 (COX-2) and nuclear factor kapp-B (NFκB). This was associated with down-regulation of Bax and up-regulation of Bcl-2 mRNA. Finally, CAPE prevented induced indomethacin-induced decrease in heat shock protein 70 (HSP70) in gastric tissues. In conclusion, CAPE possesses the ability to prevent indomethacin-induced gastric ulcer in rats. This involves, at least partially, antioxidation, anti-inflammation, anti-apoptosis and enhancement of HSP70 expression.

Components study on gastroprotective effect and holistic mechanism of the herbal pair Alpinia officinarum - Cyperus rotundus based on spectrum-effect relationship and integrated transcriptome and metabolome analyses.

ETHNOPHARMACOLOGICAL RELEVANCE: The herbal pair Alpinia officinarum-Cyperus rotundus (HPAC) has an extended history of use in the treatment of gastric ulcers, and its curative effect is definite. AIM OF THE STUDY: To explore the material basis and holistic mechanism of HPAC on ethanol-induced gastric ulcers. MATERIALS AND METHODS: Three chemometrics, GRA, OPLS, and BCA, were used to construct the spectrum-effect relationship between the HPLC fingerprints of HPAC extracts and the bioactivity indices (cell viability; the levels of TNF-α, IL-6, COX-2, and PGE2; and wound healing rate) against GES-1 cell damage to screen the bioactive ingredients. The bioactive components were isolated and validated in vitro. Simultaneously, the effects of HPAC with concentrated bioactive ingredients was tested on ethanol-induced gastric ulcers in vivo, and the mechanism was investigated using transcriptomics and metabolomics. The mechanism was further validated by Western blotting. Finally, the contents of the main components of HPAC were determined before and after compatibility. RESULTS: Twelve bioactive components were screened, and the structures of nine compounds were confirmed. An in vitro verification test showed that DPHA and galangin could protect GES-1 cells from injury, and that their content increased after compatibility. The CH2Cl2 fraction of HPAC (HP-CH2Cl2) can protect mice from ethanol-induced gastric mucosal injury by reducing hemorrhage and decreasing inflammatory cell infiltration. Western blot analysis indicated that this fraction may up-regulate TRPV1 protein and down-regulate PI3K and AKT proteins. CONCLUSIONS: DPHA and galangin may be the bioactive components against ethanol-induced GES-1 cell injury. HP-CH2Cl2 may exert gastroprotective effects by regulating PI3K, AKT and TRPV1 proteins.

Chemical components and protective effects of Atractylodes japonica Koidz. ex Kitam against acetic acid-induced gastric ulcer in rats.

BACKGROUND: Atractylodes japonica Koidz. ex Kitam. (A. japonica, Chinese name: Guan-Cangzhu, Japanese name: Byaku-jutsu), a perennial herb, which is mainly distributed in northeast area of China, it's often used to treat digestive system diseases such as gastric ulcer (GU). However, the mechanism of its potential protective effects against GU remains unclear. AIM: To investigate the protective effects of A. japonica on acetic acid-induced GU rats. METHODS: The chemical constituents of A. japonica were determined by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) analysis. The rat model of GU was simulated by acetic acid method. The pathological changes of gastric tissues were evaluated by hematoxylin-eosin stain, the levels of epidermal growth factor (EGF), EGF receptor (EGFR), nuclear factor kappa-B (NF-κB), interleukin-1ß (IL-1ß), IL-10, Na+-K+-ATPase (NKA) in serum and gastric tissues were determined by enzyme-linked immunosorbent assay, and the mRNA expressions of EGFR, NF-κBp65, IkappaBalpha (IκBα) and Zonula Occludens-1 (ZO-1) in gastric tissues were determined by real-time reverse transcription polymerase chain reaction, and the efficacy was observed. Then, plasma metabolomic analysis was performed by UPLC-MS/MS to screen the specific potential biomarkers, metabolic pathways and to explore the possible mechanisms. RESULTS: 48 chemical constituents were identified. Many of them have strong pharmacological activity, the results also revealed that A. japonica significantly improved the pathological damage of gastric tissues, increased the expression levels of IL-10, IκBα related to anti-inflammatory factors, decreased the expression levels of IL-1ß, NF-κB, NF-κBp65, related to proinflammatory factors, restored the levels of factors about EGF, EGFR, ZO-1 associated with ulcer healing and the levels of factors about NKA associated with energy metabolism. Metabolomic analysis identified 10 potential differential metabolites and enriched 7 related metabolic pathways. CONCLUSION: These findings contribute to the understanding of the potential mechanism of A. japonica to improve acetic acid-induced GU, and will be of great importance for the development and clinical application of natural drugs related to A. japonica.

The Gastroprotective Effect of Walnut Peptides: Mechanisms and Impact on Ethanol-Induced Acute Gastric Mucosal Injury in Mice.

The objective of this research was to explore the protective impact of walnut peptides (WP) against ethanol-induced acute gastric mucosal injury in mice and to investigate the underlying defense mechanisms. Sixty male BALB-c mice were divided into five groups, and they were orally administered distilled water, walnut peptides (200 and 400 mg/kg bw), and omeprazole (20 mg/kg bw) for 24 days. Acute gastric mucosal injury was then induced with 75% ethanol in all groups of mice except the blank control group. Walnut peptides had significant protective and restorative effects on tissue indices of ethanol-induced gastric mucosal damage, with potential gastric anti-ulcer effects. Walnut peptides significantly inhibited the excessive accumulation of alanine aminotransferase (ALT), aspartate transferase (AST), and malondialdehyde (MDA), while promoting the expression of reduced glutathione (GSH), total antioxidant capacity (T-AOC), glutathione disulfide (GSSG), and mouse epidermal growth factor (EGF). Furthermore, the Western blot analysis results revealed that walnut peptides significantly upregulated the expression of HO-1 and NQO1 proteins in the Nrf2 signaling pathway. The defensive impact of walnut peptides on the gastric mucosa may be achieved by mitigating the excessive generation of lipid peroxides and by boosting cellular antioxidant activity.