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.

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.

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.

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.

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

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

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.

Dose-dependent protective effects of Lactobacillus rhamnosus GG against stress-induced ulcer.

BACKGROUND: Stress-related diseases are on the rise and stress is one of the common factors that lead to ulcer. Stress-induced mucosal bleeding is a serious complication observed in many critically ill patients. Due to the harmful side effects of proton pump inhibitors, natural and active alternative treatment methods for peptic ulcer treatment that are safe in terms of side effects are an urgent need for human health. We aimed to investigate the dose-dependent protective effects of Lactobacillus rhamnosus GG (LGG) against stress ulcer induced by cold restraint stress in rats. This study was performed in a total of 42 rats, in control group (C), stress group (S), pantoprazole (20 mg kg-1 day-1) group (P), LGG (3 × 108 cfu mL-1 day-1) + stress group (M1), LGG (15 × 108 mL-1 day-1) + stress group (M5) and LGG (30 × 108 mL-1 day-1) + stress group (M10) (each n = 7). Ulceration areas (mm2) were determined quantitatively with ImageJ software. Glucocorticoid, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels were determined by ELISA and malondialdehyde levels were determined by spectrophotometric measurement. Histopathological examinations were performed in gastric tissue. RESULTS: Therapeutic dose of LGG increased CAT, SOD and GPx levels; prevented excessive activation of the hypothalamic-pituitary-adrenal axis; reduced ulceration and bleeding in the gastric mucosal layer; and provided stabilization of mast cells. CONCLUSIONS: We can suggest that LGG may be beneficial for reducing the negative effects of stress on the body, for protecting against ulcer disease and for reducing or preventing the risk of stress-induced gastrointestinal bleeding in patients staying in intensive care units. © 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Gastroprotective Effect of GABA in Metabolic Stress.

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.

[Protective effect of Albizia chinensis saponin on ethanol-induced gastric mucosal injury in rats focus on mucus and mucosal barriers].

This study aims to explore the protective effect of Albizia chinensis saponin on ethanol-induced acute gastric ulcer in rats and elucidate its mechanisms. SD rats were deprived of water for 24 hours before the experiment. The control group and model group were administered water by gavage, and the positive drug group received rabeprazole sodium solution(40 mg·kg~(-1)) by gavage. The experimental groups were given different doses of Albizia chinensis saponin solution(3, 10, and 30 mg·kg~(-1)). After 30 minutes, the control group received 1.5 mL of water by gavage, while the other groups were administered an equal volume of 95% ethanol for modeling. After six hours, the rats were killed by cervical dislocation, and the stomachs were collected. The ulcer area was measured, and the ulcer index was calculated. Hematoxylin-eosin(HE) staining was performed to assess histopathological changes in gastric tissue. Periodic acid-Schiff(PAS) staining was used to evaluate the distribution of gastric mucosal surface mucus. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of phospholipids and aminohexose in the gastric mucosa. Western blot was performed to determine the expression levels of the bicarbonate transporter, matrix metalloproteinase, and tight junction-associated proteins in gastric tissue. Immunohistochemistry(IHC) staining was conducted to quantify the number of positive cells for secreted mucin and tight junction-associated proteins. The results showed that the gastric tissue surface of rats in the control group was smooth without ulceration, and the gastric ulcer index of rats in the model group was 35±11. Albizia chinensis saponin at doses of 3, 10, and 30 mg·kg~(-1) resulted in inhibition rates of gastric ulcer of 46%(P<0.01), 85%(P<0.001), and 100%(P<0.001), respectively. Severe disruption of gastric mucosal structure and absence of the mucus layer were observed in the model group. Compared with the model group, the Albizia chinensis saponin group showed intact gastric mucosal surface mucus layer, significantly increased levels of phospholipids and aminohexose in the mucus, increased number of MUC5AC positive cells, and upregulated expression levels of the bicarbonate transporter SLC26A3 and CFTR. It also showed decreased phosphorylation of JNK and c-Jun, reduced expression levels of MMP-8, elevated expression of TIMP-1, and increased expression levels of Occludin and ZO-1. In conclusion, Albizia chinensis saponin enhances the function of the mucus-bicarbonate barrier by upregulating the content of MUC5AC, phospholipids, and aminohexose and increasing the expression levels of the bicarbonate transporter SLC26A3 and CFTR. Moreover, Albizia chinensis saponin exerts its protective effects on gastric ulcers by inhibiting the JNK signaling pathway to prevent excessive activation of MMP-8, thereby reducing the degradation of Occludin and ZO-1 and enhancing the mucosal barrier function. In summary, Albizia chinensis saponin exerts its anti-gastric ulcer effects by simultaneously enhancing the mucus barrier and the mucosal barrier.

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.

EXPERIMENTAL STUDY OF THE EFFECT OF MINERAL WATERS ON THE GASTRIC MUCOSA OF WISTAR RATS.

Acid-related diseases (ARD) are the most common among digestive diseases. The main goals of therapy of ARD are to reduce the influence of aggression factors (production of HCl, pepsin) and increase the protective properties of the mucous membrane of the upper digestive tract. Also currently in medicine, one of the therapeutic and preventive methods is the use of chloride-hydrocarbonate sodium boron mineral waters. In this study, we compared the efficacy of table mineral waters in the therapy of induced gastropathy in Wistar rats. The study of the effect of mineral waters on the gastric mucosa of Wistar rats has provided valuable information that can be applied in medical practice for the treatment and prevention of various diseases of the gastrointestinal tract in humans. Careful analysis of the data obtained has shown that certain types of mineral waters can significantly reduce inflammatory processes and promote regeneration of the gastric mucosa, which makes them a useful addition to traditional treatment methods such as pharmacotherapy.

Gastro-Protective and Therapeutic Effect of Punica granatum against Stomach Ulcer Caused by Helicobacter Pylori.

Gastric ulcer is a chronic condition that occurs when the mucosa of the stomach is broken. There is a physiological equilibrium between aggressive factors and mucosal defense. The purpose of this research was to compare the prevention level and efficiency of herbal medicinal plants (Punica granatum) to the omeprazole drug. Many groups were prepared from Albino male rats, the first control group (inoculate with H. pylori and fed with standard pellet), the Second group, rats inoculated by H. pylori and prevented with Punica granatum aqueous extracts (PGAE) in two dosages (250mg/kg, 500mg/kg), and last group inoculated by H. pylori and prevented with standard drug omeprazole at the dose (20mg/kg). The results showed that the Ulcer Inhibition % of Punica granatum with a high dose of 500mg/kg and a low dose of 250mg/kg was 84.60±5.48 and 42.87±7.14, respectively. While in the omeprazole treatment group, Ulcer Inhibition % was 24.50±6.35 and this Ulcer Inhibition %  in the Punica granatum treatment groups was significant compared to the omeprazole treatment group and the control group (P=0.0001). PGAE displayed a significant lessening in stomach index and infectious cell proliferation with much cell damage. Although the result of the current study improves, a high dosage of aqueous extracts of plants has more effectiveness than a low dosage of aqueous extracts plants.

Gastro-protective effect of l-arginine against nitric oxide deficiency-related mucosal injury induced by indomethacin: Does age matter?

Gastric ulcer is a common disease with increased prevalence in the aged population. Aged gastric mucosa has increased susceptibility to injury along with nonsteroidal anti-inflammatory drugs use due to impaired mucosal defense and decreased vasodilator release. We investigated whether l-arginine could protect against age-related gastric ulceration induced by indomethacin. Aged and adult male Wistar rats were administered sole and combined treatment of  l-arginine and Nω -nitro-l-arginine methyl ester ( l-NAME) before induction of gastric ulceration by indomethacin. The gastroprotective effect of  l-arginine was displayed only in adult rats with indomethacin-induced gastric ulceration, as evidenced by a significant decrease in ulcer index, oxidative stress parameters, and mucosal myeloperoxidase activity along with increased mucosal PGE2 levels. Interestingly, the mucosal gene expressions of NF-кB, iNOS, and COX-2 were significantly suppressed by  l-arginine pretreatment and aggregated upon pretreatment with  l-NAME in both adult and aged rats treated with indomethacin. In conclusion,  l-arginine protected the rats' gastric mucosa against indomethacin-induced gastric ulceration, possibly, at least in part, by enhancement of mucosal nitric oxide/PGE2 content along with suppressing gastric inflammation and oxidative stress. This study supposed that the gastroprotective effect of  l-arginine depends on aging, and even so, the adoption of a new approach to gastric ulcer treatment for the aged population is warranted.

Stress Ulcer Prophylaxis in Cardiac Surgery: A Retrospective Cohort Study to Analyze the Effects of SUP Cessation.

INTRODUCTION: Upper gastrointestinal bleeding (UGIB) is an important complication among critically ill adults, especially those having cardiac surgery as management is complicated by the requirement for antiplatelet/anticoagulant therapy. As a result, stress ulcer prophylaxis (SUP) has become routine practice in many centers, utilizing either proton pump inhibitors (PPIs) or histamine-2 receptor blockers (H2RBs). Recent evidence from the PEPTIC trial indicated an increase in mortality risk among cardiac surgery patients receiving PPIs compared to H2RBs. Considering these findings, alongside practical difficulties surrounding the transition to H2RBs as a prophylactic agent in New Zealand, Wellington Hospital intensive care unit elected to discontinue routine PPI use for SUP in cardiac surgery patients. A retrospective study was conducted to assess patient outcomes following the discontinuation of routine SUP. METHOD: A retrospective cohort study was conducted of all adult patients who underwent cardiac surgery at Wellington Hospital between February/2018 and January/2022, and divided patients into cohorts before and after the discontinuation of routine use of SUP on the 31st of January 2020. The primary outcomes were the rate of UGIB, oesophagogastroduodenoscopy (OGD) and 180-day postoperative mortality. Secondary outcomes included rates of postoperative Clostridium difficile enteritis, pneumonia, deep sternal wound infection, and length of stay of the index admission. RESULTS: The rate of UGIB statistically significantly increased since the cessation of routine SUP in January 2020 (2.4% vs 5.4%, P-value = .004). This finding was mirrored with the increased rates of OGD (1.9% vs 4.0%, P-value = .005). There were no significant changes in 180-day mortality, hospital length of stay, or any of the postoperative infective complications analyzed, pneumonia, deep sternal wound infection, or C difficile enteritis. CONCLUSION: This study suggests an association between routine use of SUP and reduced rates of clinically significant UGIB and OGD requirements in cardiac surgery patients without increasing risk of infective complications or postoperative mortality.

Atractylodes Processing Products Protect against Gastric Ulcers in Rats by Influencing the NF-κB-MMP-9/TIMP-1 Regulatory Mechanism and Intestinal Flora.

Atractylodes macrocephala Koidz. (AM) is a Chinese herbal medicine that is widely used for treating gastrointestinal diseases. However, little research has focused on it as a single medicine for treating gastric ulcers. Honey-bran stir-frying is a characteristic method of concocting AM, so we speculated that AM is more effective after this preparation process. Analysis by ultra-high-performance liquid chromatography-hybrid quadrupole-Orbitrap high-resolution mass spectrometry revealed changes in the chemical composition of raw Atractylodes (SG), bran-fried Atractylodes (FG), and honey-bran-fried Atractylodes (MFG). MFG was superior to SG and FG in improving the pathological structure of gastric tissue in rats with acute gastric ulcers, reducing inflammatory cell infiltration in gastric tissue, and significantly reducing malondialdehyde while increasing superoxide dismutase and glutathione peroxidase, and reducing the damage caused by free radical accumulation in the gastric mucosa. In addition, MFG reduced the expression of matrix metalloproteinase-9 (MMP-9), an inhibitor of metalloproteinase-1 (TIMP-1) and nuclear factor kappa-B (NF-κB)proteins, inhibited inflammatory response, and regulated the degradation and rebalancing of the extracellular matrix. Fecal microbiota analysis also revealed that MFG normalized the intestinal flora to some extent. Our study shows that AM had a protective effect on rats with alcohol-induced acute gastric ulcers before and after processing, and AM-processed products were more effective than raw ones. Compared with MF, MFG had a higher rate of ulcer inhibition and a stronger anti-inflammatory effect, and its mechanism of action was related to the NF-κB-MMP-9/TIMP-1 signaling pathway.

Comparison of Protective Effect of Aqueous and Ethanolic Extracts of Propolis against Gastric Ulceration in Rats.

This study focused on the protective effects of different types of propolis extracts on gastric mucosa in indomethacin-induced rats. The animals were divided into nine groups: control, negative control (ulcer), positive control (omeprazole), and experimental groups, which were summarized by 200, 400, and 600 mg/kg, bw for aqueous-based and ethanol, respectively. According to the histopathological evaluation, more than others, the doses of 200 and 400 mg/kg of aqueous-based propolis extracts had different degrees of positive effects on the gastric mucosa. Generally, the biochemical analyses of the gastric tissue showed a correlation with microscopic evaluations. According to the phenolic profile analysis, while pinocembrin (684.34±1.70 µg/ml) and chrysin (540.54±9.06 µg/ml) were the most abundant phenolics in the ethanolic extract, ferulic acid (53.77±0.07 µg/ml) and p-coumaric acid (52.61±0.42 µg/ml) dominated the aqueous-based extract. Also, the total phenolic content (TPC), total flavonoid content (TFC), and DPPH radical scavenging activity of the ethanolic extract showed almost nine-fold superiority compared to the aqueous-based extracts. Based on data from preclinical data, it was decided that the best doses for the main goal of the study were 200 mg and 400 mg/kg, bw for aqueous-based propolis extract.

Exploring the Effect of Deep-Sea Water on the Therapeutic Potential of the Anti-Inflammatory Response in an Indomethacin-Induced Gastric Ulcer Rat Model.

Gastric ulcers are often exacerbated by factors such as nonsteroidal anti-inflammatory drugs (NSAIDs) and inflammation, and they have a substantial impact on a significant portion of the population. Notably, indomethacin is recognized as a prominent contributor to ulcers. This study investigated this potential method, with normalization to the anti-inflammatory and antiulcer properties of deep-sea water (DSW)-derived mineral water, using an indomethacin-induced gastric ulcer model in rats. The study involved four groups (n = 6 rats/group): normal control group (CON), indomethacin-only group (IND), indomethacin with trace mineral water group (TM), and indomethacin with high magnesium low sodium water group (HMLS). For three weeks, the CON and IND groups consumed tap water, while the TM and HMLS groups had access to mineral water. Gastric ulcers were induced on the final day using indomethacin, for all groups except the CON group. The results demonstrated that HMLS intake significantly improved gastric mucosal damage, preserved mucin stability, and increased gastric thickness, indicating its potential to prevent and alleviate indomethacin-induced gastric ulcers. Furthermore, HMLS consumption led to the upregulation of key genes associated with inflammation and a reduction in inflammatory cytokines. These findings suggest that DSW-derived mineral water, and particularly its high Mg2+ content, may offer promising health benefits including anti-inflammatory and anti-ulcer properties.

Gastric protective effect of Alpinia officinarum flavonoids: mediating TLR4/NF-κB and TRPV1 signalling pathways and gastric mucosal healing.

CONTEXT: Our previous studies have found that total flavonoid of Alpinia officinarum Hance (Zingiberaceae) (F.AOH) had protective effects on gastric ulcer (GU). OBJECTIVE: To investigate the protective mechanism of F.AOH on acetic acid-induced chronic GUs in rats and ethanol-induced GES-1 cells damage. MATERIALS AND METHODS: In vivo: Gastric damage was induced in SD rats by administering acetic acid after oral treatment with F-AOH at 54, 27 and 13.5 mg/kg (2 weeks of continuous gavage). After a comprehensive evaluation of rats' serum and gastric tissue-related indicators, gene transcriptome sequencing, qPCR and Western blotting were used to investigate the mechanism further. In vivo: GES-1 cells were incubated with F-AOH (8, 4 and 2 µg/mL) for 16 h and treated with 7% ethanol for 4 h. Transwell and flow cytometry were employed to detect migration and apoptosis of cells. RESULTS: F.AOH effectively reduced the area of GUs in rats (from 11.2 ± 1.89 to 2.19 ± 0.95), reversing ethanol-induced cells apoptosis (from 23 ± 1.3 to 8.11 ± 0.93%). It also inhibited the expression of endothelin-1 (ET-1) and iNOS proteins, decreasing the levels of TNF-α IL-6 in serum, improving oxidative stress levels and increasing the expression of Bcl-2/Bax dimer genes. In addition, 4005 differentially expressed genes between the acetic acid model and the drug groups. Through experimental verification, F.AOH can inhibit the activation of TLR4/NF-κB signalling pathway and TRPV1 receptor. CONCLUSIONS: F.AOH, as an effective gastric protective plant component, had potential therapeutic value in anti-inflammatory pain and antioxidative stress gastrointestinal diseases.

Phytochemical analysis and gastroprotective effect of Stellaria media (L.) Vill. methanolic extract on piroxicam-induced gastric ulcer in Wistar rats.

Stellaria media L. has traditionally been used to treat inflammatory and gastrointestinal ailments. This study aimed to phytochemically characterize the S. media extract and explore its anti-ulcer efficacy against piroxicam-induced stomach lesions in Wistar rats. Phytochemical analysis was performed and antioxidant capacity of extract was determined using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. In vivo, piroxicam (30mg/kg) was administered to induce gastric ulceration. Gastro protective effect of S. media extract was observed at 150, 300 and 450mg/kg, respectively. While omeprazole (20mg/kg) was used as a conventional anti-ulcer drug. After oral treatment for 14 days, stomach acidic secretions, ulcerogenic indices, hematological markers and oxidative stress parameters were assessed along with histological examination. The existence of polyphenol contents in S. media extract was confirmed in correlation to a marked DPPH inhibition (IC50 27.94µg/mL). S. media extract resulted in a dose-dependent elevation in gastric pH while a decrease in acid volume, acidity and ulceration. Also, S. media extract administration restored the impaired hematological markers (RBCs, Hb, WBCs and PLTs) and decreased oxidative stress by reducing oxidants (TOS and MDA) while raising antioxidants (TAC and CAT). Furthermore, gastric histological results corroborated the aforementioned findings. Conclusively, S. media could provide a promising protective effect against drug-induced gastric ulceration.

Gastroprotective effects of Chinese Rana chensinensis skin collagen against ethanol-induced gastric ulcer in mice.

Gastric ulcer is a common gastrointestinal disease caused by excessive gastric acid secretion, which has been recognized as one of the most common causes of morbidity and mortality in the world. The skin of Rana chensinensis is rich in collagen and many previous studies have shown that it has certain bioactivity. Therefore, we extracted and purified collagen with a molecular weight less than 10000 Da from the skin of Rana chensinensis, and studied its gastric protective mechanism through the model of ethanol-induced gastric ulcer in Balb/c mice. The results showed that through macroscopic observation and significantly reduced ulcer index, it was proved that PCRCS could protect gastric mucosa and alleviate the damage of ethanol to gastric mucosa. PCRCS reduced ethanol-induced oxidative stress by boosting depleted SOD levels and dramatically lowering MDA levels, as well as significantly reducing lipid peroxidation. Additionally PCRCS (Protein Chinese Rana chesinensis Skin) additionally decreased the launch of inflammatory mediators TNF-α and IL-6 and more desirable the content material of protective elements NO and PGE2 in gastric mucosa. Based on these findings, we believe that PCRCS has potential stomach protective effects on ethanol-induced gastric ulcer, which may be achieved by inhibiting oxidative stress and stomach inflammation.