Indomethacin-induced Ulcer Research Articles

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.

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.

Gastroprotective Effect of 2,3-Dimethylquinoxaline Against Indomethacin-Induced Gastric Ulcer in Rat.

Gastric ulcers pose a significant health risk due to an imbalance between protective and aggressive factors on the mucous membrane. Nonsteroidal anti-inflammatory drug (NSAID)-induced gastric damage affects 25% of users. Quinoxaline compounds, known for their diverse biological properties, have potential applications in cancer therapy and as antimicrobial agents targeting various pathogens. Our study aimed to investigate the impact of DMQ on gastroprotective mechanisms in an experimental model of indomethacin-induced gastric ulcer. Thirty male Wistar rats were randomly assigned to five groups. Group 1 served as the control, while Group 2 received a single oral dose of IND (30 mg/kg). Groups 3 and 4 received oral DMQ (30 mg/kg and 60 mg/kg, respectively) for three days, with the final dose administered intragastrically one hour before IND administration. Group 5 received esomeprazole (30 mg/kg) orally for three days, with the final dose given one hour before IND administration. Rats were sacrificed four hours after IND induction. Indomethacin-induced ulcers were associated with epithelial damage and blood streaks on the gastric mucosa. However, DMQ significantly decreased levels of inflammatory biomarkers (TNF-α, IL-6, Cox-2, IFN-γ, and IL-β1) while increasing gastroprotective mediator prostaglandin E2 (PGE2) and mucin levels. Histopathological analysis revealed a significant reduction in ulcer-induced pathological alterations and upregulation of tumor suppressor genes (NF-κB levels) following DMQ treatment. Rats treated with Indo+DMQ showed a significant decrease in ulcer index compared to the Indo group, with mild injuries observed. DMQ demonstrated promising gastroprotective effects against IND-induced gastric ulcers, as evidenced by alterations in histopathological data and upregulation of gene expression.

Antinociceptive and anti-ulcerogenic effect of hydroethanolic stem bark extract of Ricinodendron heudelotii (Baill.) Pierre ex. Heckel (Euphorbiaceae): Involvement of the opioidergic pathway and attenuation of oxidative stress

Background and aimApproximately 80% of the population in developing countries is affected by gastric ulcers Gastric ulcers are associated with pain,and there is an urgent need for drugs that can manage both conditions. Ricinodendron heudelotii (Baill.) Pierre ex. Heckel has long been regarded used in managing gastric ulcers and pain in African Traditional Medicine. In the present study, the antinociceptive and anti-ulcer activity of Ricinodendron heudelotii (Baill.) Pierre ex. Heckel hydroethanolic stem bark extract (RHE) was evaluated. Experimental procedureThe antinociceptive effect of RHE was tested in ICR mice using the hot plate test, the glutamate-induced nociceptive test, and the formalin test. Gastric ulcers were induced in healthy male adult albino rats in acidified alcohol-induced ulcer (AAIU) and indomethacin-induced ulcer (IIU) models. After ulcer induction, the rats were treated with either RHE (30, 100, or 300 mg/kg, p.o.) or 10 mg/kg omeprazole. The stomachs of the sacrificed animals were removed for further analysis. Results and conclusionRHE (30, 100, and 300 mg/kg) exhibited an anti-nociceptive effect in the hot plate, formalin and glutamate tests. The opioid receptor antagonist, naloxone, reversed the analgesic effect, indicating that the extract may be acting via the opioidergic pathway. But compared to the model group in both AAIU and IIU, oral administration of RHE decreased ulcer index, raised pH levels, increased tissue levels of total antioxidant capacity, catalase, total thiols, and glutathione, and kept gastric histoarchitecture intact. RHE exhibited anti-nociceptive effects, possibly via the opioidergic pathway and anti-ulcer activity via reduction of oxidative stress.

Apium extract alleviates indomethacin-induced gastric ulcers in rats via modulating the VEGF and IK-κB/NF-κB p65 signaling pathway: insights from in silico and in vivo investigations

BackgroundGastric ulcers represent a worldwide health problem, characterized by erosions that affect the mucous membrane of the stomach and may even reach the muscular layer, leading to serious complications. Numerous natural products have been assessed as anti-ulcerogenic agents, and have been considered as new approaches for treatment or prevention of gastric ulcers. The present research investigated the preventive benefits of Apium graveolens L. (Apiaceae), known as celery, seed extract towards indomethacin-induced ulceration of the stomach in rats.MethodsMetabolomic profiling, employing liquid chromatography coupled to high-resolution electrospray ionization mass spectrometry (LC-HR-ESI–MS), was implemented with the aim of investigating the chemical profile of the seeds. Histopathological analysis of gastric tissues, as well as assessment of numerous inflammatory cytokines and oxidative stress indicators, confirmed the in vivo evaluation.ResultsThe prior treatment with A. graveolens seed extract resulted in a substantial reduction in the ulcer index when compared to the indomethacin group, indicating an improvement in stomach mucosal injury. Moreover, the gastroprotective effect was demonstrated through examination of the oxidative stress biomarkers which was significantly attenuated upon pre-treatment with A. graveolens seed extract. Vascular endothelial growth factor (VEGF), a fundamental angiogenic factor that stimulates angiogenesis, was markedly inhibited by indomethacin. A. graveolens seed extract restored this diminished level of VEGF. The dramatic reductions in NF-κB protein levels indicate a considerable attenuation of the indomethacin-induced IKκB/NF-κB p65 signaling cascade. These activities were also correlated to the tentatively featured secondary metabolites including, phenolic acids, coumarins and flavonoids, previously evidenced to exert potent anti-inflammatory and antioxidant activities. According to our network pharmacology study, the identified metabolites annotated 379 unique genes, among which only 17 genes were related to gastric ulcer. The PTGS2, MMP2 and PTGS1 were the top annotated genes related to gastric ulcer. The top biological pathway was the VEGF signaling pathway.ConclusionA. graveolens seed extract possesses significant anti-ulcer activity, similar to famotidine, against gastric lesions induced by indomethacin in rats. It is worth highlighting that the extract overcomes the negative effects of conventional chemical anti-secretory drugs because it does not lower stomach acidity.

INVESTIGATING THE THERAPEUTIC POTENTIAL OF BENIDIPINE IN INDO-METHACIN-INDUCED PEPTIC ULCERS: AN EXPERIMENTAL STUDY IN RATS

Objective: Peptic ulcer disease is a prevalent gastrointestinal disorder associated with escalating global mortality rates and a heightened risk of gastric cancer. This study investigates the therapeutic potential of Benidipine, an L-type calcium channel blocker known for its antioxidant properties, in an indomethacin-induced peptic ulcer model in rats. Methods: Thirty-six male albino Wistar rats were divided into six groups and subjected to various drug treatments, including Indomethacin, Famotidine, and Benidipine. Stomach tissue samples were collected for analysis. Results: Macroscopic examination revealed that indomethacin significantly increased ulcer areas in the stomach tissue, while Benidipine and Famotidine treatments effectively reduced these ulcer areas. Biochemical analysis indicated that Indomethacin-induced oxidative stress, as evidenced by elevated levels of malondialdehyde, a marker of lipid peroxidation, and decreased levels of total glutathione and superoxide dismutase, are crucial antioxidants. However, Benidipine treatment mitigated these changes, restoring antioxidant levels and reducing malondialdehyde levels. Conclusion: This study demonstrates that indomethacin induces gastric damage and oxidative stress, leading to ulcer formation, while Benidipine, with its antioxidant properties, effectively counteracts these effects and exhibits comparable efficacy to Famotidine in ulcer reduction. These findings suggest that Benidipine may hold promise as a therapeutic agent for mitigating peptic ulcers induced by nonsteroidal anti-inflammatory drugs like Indomethacin, warranting further exploration in clinical settings.

Prophylactic Anti-Ulcer Effect of Aqueous Leaf Extract of Mormodica foetida (Schumach & Thonn) Against Indomethacin-Induced Ulcers in Wistar Rats

Prophylactic Anti-Ulcer Effect of Aqueous Leaf Extract of Mormodica foetida (Schumach & Thonn) Against Indomethacin-Induced Ulcers in Wistar Rats

Pomegranate Juice Attenuates Anti-ulcer in Indomethacin-induced Peptic Ulcer

Introduction: Pomegranate (Punica granatum L.) is a well-known fruit that grows in tropical and subtropical areas of the world. In this study, we wanted to find out how pomegranate juice (POMJ) affected rats with gastric ulcers caused by standard drugs. Indomethacin is the most common drug causes gastric ulcer also, most of the NSAID drugs have harmful side effects, so studies have focused on finding an alternative natural solution. Methods: In this study, 25 male albino rats were used and were split into four groups of five rats each. These groups were called control, pomegranate, indomethacin, and standard. The examination took one week to complete. Indomethacin saline suspension (100 mg/kg rat weight) caused gastric ulcers. Pomegranate peel juice (5-10%) reduced stomach ulcer area and ulcer index, gastric juice volume, and acidity. Pomegranate juice restores stomach mucus content and tissue at the histological level. Results: Rats that were given indomethacin and then given pomegranate juice were significantly less likely to get a gastric ulcer. It also lowered the ulcer index to 0.7093±0.36 showing that 52.25 % prevention. Conclusion: The study's macroscopical and microscopical results showed that pomegranate juice might be able to reduce the ulceration caused by indomethacin in a rat model. Pomegranate as a protective food supplement against gastric ulcers.

Protective Effects of Ethanol Extract from Hippophae rhamnoides L. Leaves against Indomethacin-Induced Gastric Ulcer in Rats

We aimed to determine the effects of ethanol extract of Hippophae rhamnoides L. leaves on indomethacin-induced gastric ulcer in rats. 35 male Sprague Dawley rats were divided into 7 groups (n=5) at random: healthy; Hippophae rhamnoides L. leaves ethanol extract (HR) III; indomethacin; indomethacin+famotidine; indomethacin+HRI (100 mg/kg); indomethacin +HRII (250 mg/kg) and indomethacin +HRIII (500 mg/kg). All rats except the healthy group fasted for 24 hours. At the end of this period, HR and famotidine (20 mg/kg) were administered by oral gavage to the corresponding rat groups. Five minutes after the HR treatments, 25 mg/kg of indomethacin was applied by oral gavage to all groups except the Healthy and HR III groups. Six hours after indomethacin administration, stomach tissues were removed for investigation macroscopic and biochemically (Superoxide dismutase activity, Glutathione, and Malondialdehyde levels). HR administration improved ulcerative injury in stomach tissues caused by the indomethacin-induced gastric ulcer. HR administration reduced indomethacin-induced ulcer areas. Moreover, HR treatment significantly decreased malondialdehyde levels, increased glutathione levels, and elevated superoxide dismutase activity. HR significantly improved gastric ulcer by alleviating oxidative stress that could be important in ulcer. HR may be a new potential treatment option for ulcer treatment with an antioxidant effect. These findings may provide a mechanistic basis for using HR leaves to treat gastric ulcer.

Antiulcer effects of the methanolic root extracts of Paulownia elongata on indomethacin-induced peptic ulcer in male albino rats

Medicinal plants have been the basis of treatment of various diseases in African traditional medicine as well as other forms of treatment from diverse cultures of the world. The aim of this study is to evaluate the Antiulcer Effects of the Ethanol Root Extracts of Paulownia elongata on Indomethacin-Induced Peptic Ulcer in Male Albino Rats. A total of sixteen (20) male albino rats gotten from the HEMA animal Farm, Federal Housing Estate Bajabure Gerie, ulcer was induced by administration of indomethacin (30 mg/kg, orally, Clinical isolates of four bacteria (Staphylococcus aureus, Pseudomonas aeruginosa, and Clostridium Bolulinum and Escherichia coli). The well method of the agar dilution was used to determine the antibacterial activity of the plant extracts. Were used for the antibacterial evaluation, and Gas Chromatography-Mass Spectrometry (GC-MS) analysis was used for phytochemical profiling. The study determined the phytochemical profile of methanol extracts of Paulownia elongate roots using GC-MS as displayed 20 chemical constituents, the antibacterial potential of the roots extract showed higher activity at 300 mg/kg/bwt with 18.12 + 0.9 mm on Salmonella typhi and at 400 mg/kg/bwt with inhibition rate 20.14+ 0.0 mm on Klebsiella pneumonia. The anti-ulcer potential was observed higher at 400 mg/kg/bwt in group 7 with potential of 87.71%. This activity of the crude roots extract was possible as a result of the chemical constituent observed. Thus this extract should be used as an agents to cutile diseases such as anti-microbials, anti-ulcer and well as diseases as cancer, HIV in the near feature with more research to isolate the active compounds.

GASTROPROTECTIVE ACTIVITY OF ETHYL ACETATE FRACTION OBTAINED FROM THE STEM BARK EXTRACT OF DESERT DATE (BALANITES AEGYPTIACA)

The study aimed to investigate the gastroprotective activity of the ethyl acetate fraction derived from the stem bark extract of the Desert date tree (EFDD) (Balanites aegyptiaca L. Delile; family Zygophyllaceae) using ethanol and indomethacin-induced ulcer models in Wistar rats. The study was conducted using Wistar rats and divided them into five groups (n=5). Group 1 received 10% Tween 20 (1 ml/kg), which served as the control group. Group 2 was administered the standard drug, omeprazole (20 mg/kg). Groups 3-5 were the extract groups and received doses of 125, 250, and 500 mg/kg, respectively, of EFDD. Two ulcer models were used in the study namely ethanol-induced ulcers and indomethacin-induced ulcers. After administration of the respective treatments, evaluation of the mean ulcer indices in each group and calculation of the percentage ulcer inhibition compared to the control group were carried out. The results indicated that the EFDD, at doses of 250 and 500 mg/kg, significantly reduced the mean ulcer indices in both the ethanol and indomethacin-induced ulcer models compared to the control group (p<0.05). This suggests that the EFDD possesses gastroprotective properties. In conclusion, the EFDD exhibits gastroprotective activity. This finding supports the traditional use of Desert date in folkloric medicine for the treatment of ulcers. However, further research is necessary to explore the underlying mechanisms responsible for the observed gastroprotective effects.

Gastroprotective and ulcer healing effects of Nauclea pobeguinii (Rubiaceae) on experimentally induced gastric ulcers in male Wistar rats.

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

Anti-ulcer Activity of Crude Extract and Fractions of Acanthus montanus (Nees) T. Anderson on Indomethacin-Induced Ulcer

Peptic ulcer disease has remained a global threat due to several complications such as perforation, gastrointestinal obstruction and organ penetration associated with the disease. This study evaluated the phytochemical composition and anti-ulcer activity of crude extract and fractions of Acanthus montanus on an indomethacin-induced ulcer in a mouse model. The plant was extracted using cold maceration in methanol and fractionated using solvents of varying polarities into their corresponding fractions. The phytochemical screening was conducted using a standard procedure. The acute toxicity test employed Lorke’s method and the anti-ulcer activity was conducted using the indomethacin-induced method. The phytochemical composition revealed the abundance of tannins, saponins, steroids/terpenoids and flavonoids in the crude extract and fractions. An acute toxicity study showed that the extract is safe even at a high dose of 5000 mg/kg. The anti-ulcer study revealed that A. montanus extract and fractions elicited a dose-dependent activity against peptic ulcer with strong curative indices of 79, 93, and 71% for the 400 mg/kg doses of methanol extract aqueous, and n-hexane fractions respectively compared with 42% index of the control. There was a dose-dependent ulcer healing with 400 mg/kg doses eliciting higher curative indices than the 200 mg/kg doses. The 200 mg/kg doses of aqueous fraction and 400 mg/kg doses ofmethanol extract, aqueous, and n-hexane fractions elicited ulcer indices significantly different (p&lt;0.05) from those of controls. The rich presence of biologically active constituents with antiulcerogenic properties in the methanol extract and fractions of A. montanus supports its use in ethnomedicine.&nbsp

Anti-Ulcer Effect on Indomethacin-Induced Ulcerated Mice of Chromolaena odorata Leaf from Vietnam and its Secondary Metabolites

Chromolaena odorata (C. odorata) (L.) R. King &amp; H. Robinson is a perennial flowering shrub with diverse habitats, including crops, grasslands, and roadsides. This plant has been widely used in Vietnamese folk medicine for gastric ulcer treatment. Hence, the present study aimed to evaluate the acute toxicity and the anti-ulcer effect of the ethanol crude extract of C. odorata leaves and its fractions against the indomethacin-induced gastric ulcer model in mice, and investigate the chemical constituents of the most active fraction. According to in vivo results, the ethyl acetate residue with the highest anti-ulcer activity significantly reduced gastric lesions in theexperimental mice model with an ulcer index of 0.73 ± 0.39 and a percentage inhibition of 26.92%. Thus, this fraction was chosen for further chemical investigation. Four pure compounds (1-4) were extracted and isolated by using chromatographic methods. Based on the nuclear magnetic resonance spectroscopy, melting temperature, mass spectrometry analysis, and compared with thepublished literature, their structures were elucidated as 1-(4-hydroxy-3-methoxyphenyl)propane- 1,2-diol (1), kaempferol-7-O-α-L-rhamnopyranoside (2), naringenin-5,7-di-O-β-Dglucopyranoside (3), and rubrosterone (4). To our best knowledge, all of these compounds were isolated for the first time from C. odorata leaves. These findings contribute to providing scientific evidence for the traditional use and phytochemicals of C. odorata leaves.&nbsp

Investigation Into Antioxidant and Antinuclear Effect and Mechanism of Sesamum Indicum Leaves in a Rodent Model

Objective: An ethanolic extract of Sesamum indicum Linn was used to test for phytochemicals, antioxidant activity, and gastroprotective effects. Study Design: Cross-Sectional Study Place of Study: Rashid Latif Medical College Lahore. Duration of Study: July 2021 to March 2022 Materials and methods: This study ulcerated Wister albino rats using pylorus ligation and indomethacin-induced ulcer screening. Ulceration required pylorus ligation. These ulcer screening models were used. An ethanolic S. indicum leaves (EESIL) at 100, 200, and 400 mg/kg (orally for 7 days) was compared against omeprazole, a common ulcer medication. The trial lasted seven days. Throughout the course of the experiment, readings were taken for the following variables: stomach content; pH; total acidity; pepsin activity ulcer score; free acidity; ulcer index (UI); percentage of inhibition of ulcers; mean mucin, pepsin, and total protein content; and ulcer index (UI). Results: In comparison to the control group, the pylorus ligation model resulted in a decrease in pepsin activity, free acidity, pepsin content, ulcer score, total protein content, and % ulcer inhibition. Moreover, the overall acidity level was lower (P&lt; 0.05 and P&lt; 0.01). EESIL-tested groups had higher mean mucin and stomach content pH (P 0.05 and P 0.01). Both findings are statistically significant. EESIL dosages (100, 200, and 400 mg/kg ) had dose-dependent gastroprotective effects. Compared to the control group, stomach metrics like UI and ulcer score dropped significantly (P&lt; 0.05 and P&lt;0.01), gastric pH increased, and ulcer percentage inhibition increased. Increased ulcer inhibition percentage. Moreover, stomach pH increased and ulcer percentage decreased. Conclusion: Antioxidant, anti-ulcer, EESIL, and EESIL compounds have antioxidant action depending on concentration. Antioxidant is connected. The study found that the EESIL's increased defensive and decreased offensive components increased its antiulcer potential. This was due to the study's revisions. The research's offensive and defensive design caused this. Keywords: Antioxidant, anti-ulcer, ethanolic extract of sesamum indicum leaves, indomethacin, pylorus ligation, ulcer index

Phytochemical Estimation and Therapeutic Amelioration of Aesculus hippocastanum L. Seeds Ethanolic Extract in Gastric Ulcer in Rats Possibly by Inhibiting Prostaglandin Synthesis.

To quantify phytochemicals using liquid chromatography and mass spectroscopy (LCMS) analysis and explore the therapeutic effect of Aesculus hippocastanum L. (AH) seeds ethanolic extract against gastric ulcers in rats. Preliminary phytochemical testing and LCMS analysis were performed according to standard methods. For treatment, the animals were divided into 7 groups including normal control, ulcer control, self-healing, AH seeds low and high doses, ranitidine and per se groups. Rats were orally administered with 10 mg/kg of indomethacin, excluding the normal control group (which received 1% carboxy methyl cellulose) and the per se group (received 200 mg/kg AH seeds extract). The test group rats were then given 2 doses of AH seeds extract (100 and 200 mg/kg, respectively), while the standard group was given ranitidine (50 mg/kg). On the 11th day, rats in all groups were sacrificed, and their stomach was isolated to calculate the ulcer index, and other parameters such as blood prostaglandin (PGE2), tissue superoxide dismutase (SOD), catalase (CAT), malonyldialdehyde (MDA), and glutathione (GSH). All isolated stomach tissues were analyzed for histopathological findings. The phytochemical examination shows that the AH seeds contain alkaloids, flavonoids, saponins, phenolic components, and glycosides. LCMS analysis confirms the presence of quercetin and rutin. The AH seeds extract showed significant improvement in gastric mucosa conditions after indomethacin-induced gastric lesions (P<0.01). Further marked improvement in blood PGE2 and antioxidant enzymes, SOD, CAT, MDA and GSH, were observed compared with self-healing and untreated ulcer-induced groups (P<0.01). Histopathology results confirmed that AH seeds extract improved the mucosal layer and gastric epithelial membrane in treated groups compared to untreated ulcer-induced groups. LCMS report confirms the presence of quercetin and rutin in AH seeds ethanolic extract. The therapeutic effect of AH seeds extract against indomethacin-induced ulcer in rat model indicated the regenerated membrane integrity, with improved cellular functions and mucus thickness. Further, improved antioxidant enzyme level would help to reduce PGE2 biosynthesis.

Expression of Concern: "Optimization of Thymoquinone-Loaded Self-Nanoemulsion for Management of Indomethacin-Induced Ulcer".

Sage Publishing and the Journal Editor hereby issue an expression of concern for the following article: Radwan MF, El-Moselhy MA, Alarif WM, Orif M, Alruwaili NK, Alhakamy NA. Optimization of Thymoquinone-Loaded Self-Nanoemulsion for Management of Indomethacin-Induced Ulcer. Dose-Response. 2021;19(2). doi:10.1177/15593258211013655 Sage Publishing was made aware of a PubPeer post that cited concerns over possible image duplication. The post has noted that Figure 2C appears to be a vertically stretched version of Figure 2B. Another commentor on the post also noted that Figure 2B and 2C appear highly similar to Figure 7B and 7C of Fahmy et al.1 When we contacted the authors for comment, they stated that their institution has conducted an investigation into the concern. The institutional investigation states that this image duplication error occurred due to an error; the lab technician responsible for capturing the images sending the two author groups the same files by accident. The institutional investigation does not address why the image was stretched and duplicated within the same publication. The raw images provided by the institution have been attached as Supplementary Information. Due to the nature of the concern, Sage issue this expression of concern to alert readers.

Cholesterol sulfate limits neutrophil recruitment and gut inflammation during mucosal injury.

During mucosal injury, intestinal immune cells play a crucial role in eliminating invading bacteria. However, as the excessive accumulation of immune cells promotes inflammation and delays tissue repair, it is essential to identify the mechanism that limits the infiltration of immune cells to the mucosal-luminal interface. Cholesterol sulfate (CS) is the lipid product of the sulfotransferase SULT2B1 and suppresses immune reactions by inhibiting DOCK2-mediated Rac activation. In this study, we aimed to elucidate the physiological role of CS in the intestinal tract. We found that, in the small intestine and colon, CS is predominantly produced in the epithelial cells close to the lumen. While dextran sodium sulfate (DSS)-induced colitis was exacerbated in Sult2b1-deficient mice with increased prevalence of neutrophils, the elimination of either neutrophils or intestinal bacteria in Sult2b1-deficient mice attenuated disease development. Similar results were obtained when the Dock2 was genetically deleted in Sult2b1-deficient mice. In addition, we also show that indomethacin-induced ulcer formation in the small intestine was exacerbated in Sult2b1-deficient mice and was ameliorated by CS administration. Thus, our results uncover that CS acts on inflammatory neutrophils, and prevents excessive gut inflammation by inhibiting the Rac activator DOCK2. The administration of CS may be a novel therapeutic strategy for inflammatory bowel disease and non-steroidal anti-inflammatory drug-induced ulcers.

Different protective capability of chlorogenic acid and quercetin against indomethacin-induced gastrointestinal ulceration.

The study compared the protective effects against indomethacin-induced GI ulceration of chlorogenic acid with quercetin in rats. Rats were orally given chlorogenic acid or quercetin (100 mg/kg; 5 days), followed by indomethacin (40 mg/kg; single dose). After 24 h, GI tissues were assessed for histopathological damages, then analysed by ELISA and western blot methods. Cell viability was measured in vitro by MTT assay. Unlike quercetin, chlorogenic acid could not prevent gastric ulcers in indomethacin-treated rats. The levels of gastric prostaglandin E2 (PGE2) and Bax/Bcl-2 ratio in the chlorogenic acid-treated group were not different from those receiving indomethacin alone. Nevertheless, both compounds alleviated jejunum ulcers through suppression of PERK/eIF-2/ATF-4/CHOP-related endoplasmic reticulum (ER) stress and decrease Bax/Bcl-2 ratio. Moreover, at 100 µM, they abolished the cytotoxicity of tunicamycin (an ER stress inducer) in gastric (AGS) and intestinal (Caco-2) cells. In silico docking studies suggested that both compounds could interact with key amino acid residues in the -catalytic domain of PERK. Chlorogenic acid and quercetin exerted comparable protective effects against indomethacin-induced intestinal ulcer through suppression of ER stress-mediated apoptosis but, unlike quercetin, chlorogenic acid offered no protection against gastric ulceration due to its -inability to increase PGE2 production.

ISOLATION OF STIGMASTEROL AND GASTROPROTECTIVE ACTIVITY OF THE ETHYL ACETATE PORTION FROM ACACIA NILOTICA LINN (FABACEAE) SEEDS

Acacia nilotica Linn is used traditionally in the treatment of various diseases, such as diarrhea, ulcer, dysentery, asthma, inflammation and cancer. The present study aimed at isolation and characterization of a steroidal compound and evaluating the gastroprotective activity of the ethyl acetate portion of A. nilotica seeds in indomethacin-induced ulcer model. Fractionation of the ethyl acetate portion using standard chromatographic techniques led to the isolation of a compound (B2-I) which on further purification and characterisation using physical, chemical and spectral analysis, and by comparison with literature values was identified as stigmasterol. The effect of ethyl acetate portion of A. nilotica on experimentally induced ulcer was dose-dependent with curative ratios of 40%, 60% and 75% at concentrations of 100, 200 and 300 mg/kg body weights respectively. It significantly (P&lt;0.05) decreased free and total acidity and increased the pH of gastric juice with respect to the indomethacin treated group. This justifies the ethnomedicinal use of A. nilotica seed as an antiulcer agent. The study recommends that A. nilotica seeds be evaluated against other ulcer models such as ethanol and stress induced ulcers.