Indomethacin-induced Gastric Ulcer Research Articles

Comparative Effect of Curcuma longa and Piper nigrum Extract and their Mixture on some Gastric Secretory Parameters of Indomethacin-induced Gastric Ulceration in Albino Rats

Peptic ulcer disease (PUD) which includes gastric and duodenal ulcer is one of the unresolved medical problems facing numerous patients in a wide range of age of both sexes worldwide. Many medicinal plants are known to exhibit antiulcer activity and some have been confirmed scientifically to possess gastro protective and antiulcer property and also found to be useful in its treatment. Among these medicinal plants turmeric (Curcuma longa) and black pepper (Piper nigrum) have been reported to possess gastroprotective potentials. However, the effect of the combination of turmeric and black pepper on some gastric secretory parameters of ulcerated rats hasn’t been considered. As a result, this study was designed to evaluate the effect of ethanol extract of Curcuma longa and Piper nigrum on some gastric secretory parameters of indomethacin induced gastric ulceration in albino rats. Total of sixty (60) albino rats was used for this study. After acclimatization for 14 days, the animals were randomly allocated into six groups (n=10).Group A (normal control): rats was fed on pellet and allowed free access to water, rats in Group B (Ulcerated control) were given only indomethacin at a dose of 50mg/Kg body weight. Animals in group C (Standard control) was given indomethacin after pre treatment with esomperazole (20mg/kg) body weight. Group D, E, and F comprised ulcerated rats pre treated with turmeric (200mg/kg body weight), black pepper (100mg/kg body weight), turmeric and black pepper (200mg/Kg + 100mg/kg respectively) body weight. Treatments with the reference drug and extracts lasted for 21 days prior to ulcer induction on the twenty-third day.4 h post ulcer induction, the animals were humanely sacrificed under chloroform anaesthesia and gastric content drained into a centrifuge tube for further studies on some gastric secretory parameters. The study showed that TA levels were significantly (p < 0.05) higher in group B compared to the control group and all other groups. Conversely, TA levels were significantly (p < 0.05) lower in groups C, D, E, and F compared to the control, with group F showing the lowest levels among these, particularly lower than groups C and E. GpH levels were significantly (p < 0.05) lower in group B when compared to groups C, D, E, and F. However, GpH levels were significantly (p < 0.05) higher in groups D and E compared to the control, with group E having higher GpH levels than group C. Additionally, pepsin levels were significantly (p < 0.05) elevated in group B relative to the control and other groups. Pepsin levels were also significantly (p < 0.05) higher in groups C, D, E, and F compared to the control, with group C having lower levels than groups D and E. It can therefore concluded based on the findings of this study that the combination of turmeric and black pepper extract had more gastroprotective effect than the individual extracts alone suggestive of the synergistic effect of these plants in the management of peptic ulcer disease. Keywords: Curcuma longa, Piper nigrum, Indomethacin and Gastric Ulceration

Comparative Effect of Curcuma longa and Piper nigrum Extract and their Mixture on some Haematological Indices of Indomethacin-Induced Gastric Ulceration in Albino Rats

Peptic ulcer disease (PUD) which includes gastric and duodenal ulcer is one of the unresolved medical problems facing numerous patients in a wide range of age of both sexes worldwide. Many medicinal plants are known to exhibit antiulcer activity and some have been confirmed scientifically to possess gastro protective and antiulcer property and also found to be useful in its treatment. Among these medicinal plants turmeric (Curcuma longa) and black pepper (Piper nigrum) have been reported to possess gastroprotective potentials. However, the effect of the combination of turmeric and black pepper on the haematological indices of ulcerated rats hasn’t been considered. As a result, this study was designed to evaluate the effect of aqueous extract of Curcuma longa and Piper nigrum on some haematological parameters of indomethacin-induced gastric ulceration in albino rats. Total of sixty (60) albino rats was used for this study. After acclimatization for 14 days, the animals were randomly allocated into six groups (n=10).Group A (normal control): rats was fed on pellet and allowed free access to water, rats in Group B (Ulcerated control) were given only indomethacin at a dose of 50mg/Kg body weight. Animals in group C (Standard control) was given indomethacin after pre-treatment with omperazole (20mg/kg) body weight. Group D,E, and F comprised ulcerated rats pre-treated with turmeric (200mg/kg body weight), black pepper (100mg/kg body weight), turmeric and black pepper (200mg/Kg + 100mg/kg respectively) body weight. Treatments with the reference drug and extracts lasted for 21 days prior to ulcer induction on the twenty-third day.4 h post ulcer induction, the animals were humanely sacrificed under chloroform anaesthesia and blood samples were collected for further haematological studies. The result obtained from this study showed that there were no significant (p > 0.05) differences in PCV, HbC, TWBC, NEUT, MON, EOS, BAS, RBC and PLT levels across all groups, with LYM being significantly (p < 0.05) different in group E compared with Group F. The study found that Curcuma longa and Piper nigrum extracts, either alone or in combination, do not significantly alter haematological indices in albino rats with gastric ulcers caused by indomethacin, suggesting they may be beneficial without negative systemic impact. However, lymphocyte levels significantly decreased in the group treated with a mixture of Curcuma longa and Piper nigrum, suggesting a potential mild immunomodulatory effect. Keywords: Haematological Indices, Indomethacin, Ulcer, Curcuma longa and Piper nigrum

Trimetazidine protects against acute indomethacin-induced gastric mucosal, hepatic, and renal injury in rats

Background: Peptic ulcers are increasingly reported as a challenging disease in clinical settings. Several medications are employed in the management of peptic ulcers. Thus far, there is no medication devoid of any adverse effects that may achieve a 100% curative rate or provide a total remedy for the ailment. Aim: We aimed to examine the healing effects of trimetazidine against indomethacin-induced gastric ulcers in albino rats. Methodology: A total of 25 rats were used, divided into five groups (each group contained five rats): a negative control group that was only treated with distilled water, a positive control group that was only treated with a single dose of indomethacin (30 mg/kg) orally, a group that received indomethacin (30 mg/kg) and low doses of trimetazidine (17.5 mg/kg) orally, a group that received indomethacin (30 mg/kg) and medium doses of trimetazidine (35 mg/kg) orally, and a group that received indomethacin (30 mg/kg) and high doses of trimetazidine (52.5 mg/kg) orally. The induction of gastric ulcers occurred on the first day of the experiment through the administered indomethacin and, subsequently, the rats were treated orally with either trimetazidine or distilled water, three times daily, for 7 days. Serum urea, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin levels were measured. Stomachs were excised from the rats’ bodies and opened along the greater curvature; they were then rinsed with saline, extended on a white corkboard, and examined macroscopically. The stomach tissues were also processed in order to generate microscopic slides for microscopical examination. Results: Indomethacin administration caused multiple ulcerations in the gastric mucosa, significant elevations in serum urea, creatinine, AST, and ALT levels, and a significant reduction of the serum albumin levels. The treatment with trimetazidine significantly healed the indomethacin-induced gastric ulcers. Conclusion: The present study indicates that the nonsteroidal anti-inflammatory drug (NSAID) indomethacin can induce substantial gastric ulcers, which may be linked to a direct toxic effect on the histological architecture of the gastric linings in addition to the reduction of blood flow to gastric mucosa; this effect can be treated by administration of trimetazidine. Ultimately, this study suggests that administering the optimal dosage of trimetazidine can be advantageous in treating stomach ulcers caused by NSAIDs. Moreover, the study suggests that the indomethacin-induced liver and renal dysfunction can also be alleviated by the use of trimetazidine.

β-Citronellol: a potential anti-inflammatory and gastro-protective agent-mechanistic insights into its modulatory effects on COX-II, 5-LOX, eNOS, and ICAM-1 pathways through in vitro, in vivo, in silico, and network pharmacology studies

BackgroundThe current study aimed to evaluate the anti-inflammatory, anti-oxidant, and pronounced gastro-protective activities of β- Citronellol using in vitro, in vivo assays and in silico approaches.MethodsIn vitro assays, denaturation of bovine serum albumin, egg protein, and human Red Blood Cells (RBCs) membrane stabilization were performed, using Piroxicam as standard. For in vivo assessment, Histamine (0.1 ml from 1% w/v) and Formaldehyde (0.1 ml from 2% v/v) were used to mediate inflammation. In silico molecular docking and network pharmacology were employed to probe the possible target genes mediating gastroprotective effect of β-Citronellol at 25, 50, and 100 mg/kg, using indomethacin-induced (25 mg/kg i.p) gastric ulcer in rats. Moreover, Gastric tissues were evaluated for morphological, histopathological, and bio-chemical analysis of PGE2, COX-I, COX-II, 5-LOX, eNOS, ICAM-1, oxygen-free radical scavengers (SOD, CAT), and oxidative stress marker (MDA).Resultsβ-Citronellol prevented denaturation of proteins and RBCs membrane stabilization with maximum effect observed at 6,400 µg/mL. Citronellol decreased rat’s paw edema. Network pharmacology and docking studies revealed gastro-protective potential of Citronellol possibly mediated through arachidonic acid pathways by targeting COX-I, COX-II, PGE2, and 5-LOX. Citronellol reduced the ulcer indices, and histopathological changes. Further, β-Citronellol (50 and 100 mg/kg) increased gastric PGE2, COX-1, and eNOS; while suppressing COX-2, 5-LOX and ICAM-1. Citronellol markedly enhanced the oxidative balance in isolated rat stomach tissues.ConclusionsThe anti-inflammatory, anti-oxidant, and gastro-protective effects of β-Citronellol against indomethacin-induced gastric ulcer model in rats through mediating COX-I, COX-II, PGE2, 5-LOX, eNOS, and ICAM-1 inflammatory markers.Graphical abstract

Protective Effects of Infliximab on Indomethacin-Induced Gastric Ulcer in Rats: The Role of MAPK/NF-KB p65 Signaling Pathway

Protective Effects of Infliximab on Indomethacin-Induced Gastric Ulcer in Rats: The Role of MAPK/NF-KB p65 Signaling Pathway

Mitigation of Indomethacin-Induced Gastric Ulcer in Rats by 2,3-Dichloro-6-(trifluoromethoxy) quinoxaline: Modulation of Inflammatory Mechanisms

Objective: To investigate the gastroprotective influence of 2,3-Dichloro-6-(trifluoromethoxy) quinoxaline in a rat model of indomethacininducedgastric ulcers. Methods: Thirty male Wistar rats were randomly divided into five groups (n = 6) as follows: Group 1 (control), Group 2 (indomethacin only, 30 mg/kg), Group 3 (indomethacin and 2,3-Dichloro-6-(trifluoromethoxy) quinoxaline, 30 mg/kg), Group 4 (indomethacin with 2,3-Dichloro-6-(trifluoromethoxy) quinoxaline, 60 mg/kg), and Group 5 (indomethacin with esomeprazole, 30 mg/kg). The efficacy of 2,3-Dichloro-6-(trifluoromethoxy) quinoxaline in mitigating gastric ulcers induced by indomethacin in rats was evaluated based on gastric morphology, histopathology, and inflammatory biomarkers. Results: Indomethacin-induced stomach ulcers resulted in epithelial damage and blood streaks on the gastric mucosa. However, treatmentwith indomethacin and 2,3-Dichloro-6-(trifluoromethoxy) quinoxaline (60 mg/kg) significantly (P < 0.05) reduced ulcers compared to the indomethacin-only group. Inflammatory cells were observed in the indomethacin group, while the 60 mg/kg 2,3-Dichloro-6- (trifluoromethoxy) quinoxaline-treated group exhibited the restoration of normal epithelial tissue and minimal inflammatory cells, similar to the control and esomeprazole-treated groups. Furthermore, 2,3-Dichloro-6-(trifluoromethoxy) quinoxaline significantly decreased inflammatory biomarkers (TNF-α, IL-6, INF-γ, and IL-β1) and increased gastroprotective mediator levels (PGE2 and mucin), both with P-values below 0.05, in contrast to the effects of indomethacin. Conclusion: This study provides clinical evidence highlighting the gastroprotective properties of 2,3-Dichloro-6-(trifluoromethoxy) quinoxaline. Its initial application reveals, for the first time, its efficacy in treating gastric ulcers induced by indomethacin. However, further tests are warranted to validate these findings.

The role of camel milk as a protective factor on rats infected with indomethacin-induced gastric ulcer

This research was conducted to evaluate the nutritional content of camel milk and the difficulties that accompany them when taken with indomethacin. The results observed that camel milk is a rich source of nutritional values and antioxidants. The biological experimental was divided into six groups. The first group was control negative, and the groups G2, G3, G4, and G5 had orally one dose of indomethacin (30 mg/kg body weight) to induce ulcers. The G2 was considerably a positive control, and the groups G3, G4, and G5 had orally 5, 10, and 15 mL/kg body weight daily camel milk. The results observed that camel milk markedly raised concentrations of enzymatic antioxidants while concurrently lowering malondialdehyde levels in comparison to the positive group. However, rats taken orally 15 mL/kg camel milk showed significantly lower serum IL-6 and tumor necrosis factor-α concentration compared to 5 and 10 mL/kg camel milk. Rats given indomethacin showed a significant decrease in cyclooxygenase (COX-2) and prostaglandin E2 (PGE2) levels and also a significant increase in cytochrome P450 reductase activity. These results were based on the measurements of cyclooxygenase activity, PGE2 concentration, and cytochrome P450 reductase activity in the gastric tissues. The results from macroscopic examination and histopathological examination of gastric ulcers in normal and treated rats groups with camel milk confirmed the above results by serum and gastric tissue. Therefore, camel milk has a potent ulcer-healing impact on gastrointestinal injury caused by indomethacin. The potential cytoprotective mechanism and antioxidant characteristics of camel milk may be responsible for its antiulcer efficacy.

Attenuation of adjuvant-induced arthritis with carnosic acid by inhibiting mPGES-1, COX-2, and bone loss in male SD rats

Objective Rheumatoid arthritis (RA), a chronic inflammatory disease, is characterized by joint swelling, cartilage erosion, and bone destruction. This study investigated the therapeutic efficacy of Carnosic acid (CA), a natural compound with anti-inflammatory and antioxidant properties, in an adjuvant-induced arthritis model. Methods Paw swelling and arthritis index were measured. Oxidative stress markers, including lipid peroxidation and antioxidant enzyme levels, were assessed. Synovial tissue was analyzed for pro-inflammatory markers using real-time Q-PCR and Western blotting. The expression of mPGES-1 was determined by Western blotting. Peripheral neuropathic pain was assessed using cold and mechanical allodynia tests. Bone loss was quantitatively assessed through microcomputed tomography (μCT) scanning of femurs and X-ray radiography. Indomethacin-induced gastric ulcers were evaluated. Molecular docking studies were conducted to analyze the binding affinity of CA to mPGES-1. Results The CA treatment not only demonstrated a significant reduction in joint inflammation and paw swelling but also mitigated oxidative stress and improved the antioxidant defence system. CA inhibited microsomal prostaglandin E synthase-1 (mPGES-1) expression and the expression of pro-inflammatory molecules such as inducible nitric oxide synthase (iNOS) and cyclooxygenases-2 (COX-2), thus attenuating the arthritis symptoms without severe gastrointestinal side effects. Additionally, it inhibited the expression of pro-inflammatory molecules such as iNOS and COX-2, contributing to the reduction of arthritis symptoms. Notably, CA treatment prevented the common side effects of traditional RA treatments like corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs), including weight loss, bone degradation, and gastric ulcers. Conclusions These findings suggest that CA, through specific enzyme inhibition, offers a compelling alternative therapeutic approach for RA. Further research is warranted to explore the potential of CA in other arthritis models and its suitability for human RA treatment.

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

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

Atractylenolide I Alleviates Indomethacin-Induced Gastric Ulcers in Rats by Inhibiting NLRP3 Inflammasome Activation.

Atractylodes macrocephala Koidz, a traditional Chinese medicine, contains atractylenolide I (ATR-I), which has potential anticancer, anti-inflammatory, and immune-modulating properties. This study evaluated the therapeutic potential of ATR-I for indomethacin (IND)-induced gastric mucosal lesions and its underlying mechanisms. Noticeable improvements were observed in the histological morphology and ultrastructures of the rat gastric mucosa after ATR-I treatment. There was improved blood flow, a significant decrease in the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, and IL-18, and a marked increase in prostaglandin E2 (PGE2) expression in ATR-I-treated rats. Furthermore, there was a significant decrease in the mRNA and protein expression levels of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), cysteinyl aspartate specific proteinase-1 (caspase-1), and nuclear factor-κB (NF-κB) in rats treated with ATR-I. The results show that ATR-I inhibits the NLRP3 inflammasome signaling pathway and effectively alleviates local inflammation, thereby improving the therapeutic outcomes against IND-induced gastric ulcers in rats.

Gastroprotective effect of SKM-Gelcocid suspension on indomethacin induced gastric ulcer in female Wistar rats

Background: Peptic ulcer causes painful ulcers or lesions in the stomach or duodenum. It is also known as a gastric ulcer, which is damage to the gastric wall or lower portion of the esophagus. In the allopathic system, many medications such as H2 receptor antagonists, and anti-H. pylori, proton pump inhibitors, and others with rapid therapeutic activities were utilized to treat peptic ulcers.Purpose: The main aim of this work is to report an in-vivo gastro protective investigation of Saminathapuram Karuppana Gounder Maeilanandhan- Gelcocid suspension (SKM-GS), an Ayurveda formulation, using indomethacin-induced gastric ulcer rats.Study Design and Methods: In the present study we have reported the gastroprotective effect of SKM-GS, an Ayurveda formulation. Indicators such as gastric ulcer area, ulcer index, gastric wall mucus, non-protein sulfhydryl groups (NP-SH), and anti-oxidant enzymes secreted by treatment with SKM-GS on Indomethacin-induced ulcers in female Wistar rats.Result: The results showed a significant (p>0.001) reduction in gastric ulcer area, ulcer index, and an increase in ulcer preventive index. It further revealed an increase in gastric wall mucus and NP-SH secretion. Treatment with SKM-GS showed decreased levels of malondialdehyde (MDA) levels and increased levels of glutathione (GSH) and glutathione peroxidase (GPx) enzymes in the indomethacin-induced gastric ulcer rats. Female Wistar rats when treated with 200 mg/kg and 400 mg/kg of SKM-GS identical to Lansoprazole (Lanso) showed an increase in gastroprotective activity in a dose-dependent manner.Conclusion: The SKM-GS's gastro-protective properties were similar to the well-known anti-ulcer, Lansoprazole. These effects may be due to antioxidant activity.

Apigenin attenuates indomethacin-induced gastric ulcer in rats: emphasis on antioxidant, anti-inflammatory, anti-apoptotic, and TGF-β1 enhancing activities.

Gastric ulcer disease is associated with significant morbidity and mortality rates. The most two common causes of the ulcer are Helicobacter pylori infection and non-steroidal anti-inflammatory drugs. In the past few decades, a significant decrease in the morbidity and mortality rate has been observed probably due to the discovery of proton pump inhibitors. However, the medications used to treat gastric ulcers impose several nauseous side effects. Therefore, recent studies focus on the use of natural products to treat gastric ulcers. In the current study, gastric ulcer was effectively induced using indomethacin, and the protective effect of apigenin, a potent antioxidant flavonoid, was assessed in comparison to omeprazole. The administration of a single oral indomethacin (50mg/kg) induced gastric ulcer as manifested by hemorrhagic lesions in the gastric mucosa, increased ulcer index, and histopathological alterations. Indomethacin also increased lipid peroxidation, decreased the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase, increased the immunoreactivity of the inflammatory markers cyclo-oxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α), and nuclear factor-kappa B (NF-κB), increased the transcription of the apoptotic marker, Bax, and decreased that of the antiapoptotic Bcl-2. Indomethacin also decreased the immunoreactivity of transforming growth factor-beta 1 (TGF-β1). On the other hand, pretreatment with apigenin (10 and 20mg/kg) resulted in a dose-dependent improvement in the macroscopic and microscopic features of the gastric mucosa in a manner comparable to that of omeprazole. The gastroprotective effects of apigenin may be attributed to its anti-inflammatory, anti-antioxidant, and anti-apoptotic activities as well as enhancing the expression of TGF-β1. Further experimental and clinical research is required to confirm activity of apigenin as anti-ulcer agent.

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

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

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

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. Control group - Physiological saline was administered daily for 10 days. Indo group-Physiological saline was administered daily for 10 days. Ranitidine + Indo group 5mg/kg ranitidine dose was administered daily for 5 days. On day 11, a single dose of 100mg/kg of indomethacin was given to the same group. Probiotic + Indo group 1ml/kg of oral probiotic bacteria was administered daily for 10 days. On day 11, a single 100mg/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. 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). 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.

Tilapia Head Glycolipid Alleviates Indomethacin-Induced Gastric Ulcer via Regulating Oxidative Stress and Inflammation Through COX/PGE2 Signaling Pathway in Adult Rats

Tilapia Head Glycolipid Alleviates Indomethacin-Induced Gastric Ulcer via Regulating Oxidative Stress and Inflammation Through COX/PGE2 Signaling Pathway in Adult Rats

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-1β, IL-6, TNF-α, and MAPK signaling pathways, without compromising gastric acidity.

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

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

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.

Potential effects of Curcumin, Thyme, and Chamomile Oils against Indomethacin-induced Gastric ulcer in male Wister Albino rats

Potential effects of Curcumin, Thyme, and Chamomile Oils against Indomethacin-induced Gastric ulcer in male Wister Albino rats

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

ABSTRACT The purpose of this study was to evaluate the effects of syringic acid, an anti-oxidant, on indomethacin induced gastric ulcers in rats. Experimental groups were control, ulcer, ulcer treated with 20 mg/kg esomeprazole (a proton pump inhibitor that reduces acid secretion), and ulcer treated with 100 mg/kg syringic acid. Rats were pretreated with esomeprazole or syringic acid two weeks before ulcer induction. Our histopathological observations showed that either syringic acid or esomeprazole attenuated the severity of gastric mucosal damage. Moreover, syringic acid and esomeprazole pretreatments alleviated indomethacin-induced damage by regulating oxidative stress, inflammatory response, the level of transforming growth factor-β (TGF-β), expressions of COX and prostaglandin 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.