Gastric Ulcer Model Research Articles

An integrated network analysis, RNA-seq and in vivo validation approaches to explore the protective mechanism of Mongolian medicine formulae Ruda-6 against indomethacin-induced gastric ulcer in rats.

Gastric ulcer (GU) is one of the most prevalent digestive diseases that seriously affects people's health. Previous studies have demonstrated the anti-GU effect of Ruda-6 (RD-6), a classic formulae of traditional Mongolian medicine. However, the underlying mechanism of RD-6 against GU remains elusive. Thus, we conducted an integrative approach of network analysis, RNA-seq, and in vivo validation experiment to elucidate the therapeutic mechanisms of RD-6 in preventing GU. A network analysis was performed to predict the potential targets of RD-6. Rats were pretreated with RD-6 at different doses for 21days, followed by GU induction with indomethacin injection. The ulcer index and inhibition rates were calculated, and the levels of inflammatory related factors were determined by ELISA. The gastroprotective mechanism of RD-6 against ulceration was verified by RNA-seq and the key pathway was detected by in vivo validation. As the network analysis predicted, RD-6 exerts anti-GU effects by regulating 75 targets and 160 signaling pathways. Animal experiment results suggested that pretreatment with RD-6 significantly ameliorated the gastric mucosal injury and inflammatory response, as evidenced by a reduced ulcer index, decreased interleukin (IL)-1β, IL-6, and IL-17 levels, and increased prostaglandin E2 (PGE2) levels in the GU model rats induced by indomethacin. RNA-seq data identified four potential hub genes that were primarily involved in the IL-17 signaling pathway. Furthermore, in vivo validation experiment showed that RD-6 inhibited the IL-17 signaling pathway by down-regulating the expression of IL17RA, proto-oncogene C-Fos (FOS), IL1B and prostaglandin-endoperoxide synthase 2 (PTGS2). Taken together, the present study provides evidence that RD-6 could effectively protect against indomethacin-induced GU, which might be attributed to suppressed inflammation. The IL-17 signaling pathway may be one of the crucial mechanisms that mediates the effect of RD-6.

The Importance of Plant Extract in Improving the Microflora of the Gastrointestinal Tract in the Treatment of Diseases of the Stomach and Duodenum

The paper presents the results of studying the anti-ulcer activity of a combination of complex plant extracts on experimental models of stress and acetylsalicylic gastric ulcers when administered per os extract at a dose of 150 mg/ kg to laboratory animals. The experiments were performed on nonlinear male rats and mongrel male mice. Determination of the Pauls index, the anti–ulcer action index (AUE) - the main criteria for evaluating the anti-ulcer activity of drugs. It is shown that in stress ulcers, the effectiveness of the extract is characterized by a decrease in large, point, stripe-shaped ulcers, a decrease in the number of ulcerative lesions in mice, the AUE index = 4.6. It was found that in the acetylsalicylic model of gastric ulcers against the background of the introduction of the extract, ulcers were detected only in 70% of animals, less pronounced damage to the gastric mucosa was observed, the AUE index is 4.5.

Therapeutic effect and mechanism of non-polysaccharide fraction of Bletillae Rhizoma in treatment of gastric ulcer based on network pharmacology and animal experiment

The present study aimed to explore the therapeutic effect and mechanism of non-polysaccharide fraction of Bletillae Rhizoma in the treatment of gastric ulcer by network pharmacology and animal experiments. UPLC-Q-TOF-MS/MS was employed to chara-cterize the chemical components of non-polysaccharide fraction of Bletillae Rhizoma, and the common targets of Bletillae Rhizoma and gastric ulcer were screened out by network pharmacology. The "drug-component-target-disease" network was constructed. Protein-protein interaction(PPI) network was established by STRING. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were performed based on Matescape database to predict the therapeutic effect and mechanism of Bletillae Rhizoma. Finally, the gastric ulcer model was induced in mice by alcohol to verify the therapeutic effect and mechanism of non-polysaccharide fraction of Bletillae Rhizoma on gastric ulcer. Forty-seven chemical components were identified from non-polysaccharide fraction of Bletillae Rhizoma, among which gymnoside Ⅰ, gymnoside Ⅱ, militarine, bletilloside A, and shancigusin I might be the main active components of non-polysaccharide fraction of Bletillae Rhizoma against gastric ulcer. PPI network analysis revealed core targets such as albumin(ALB), serine/threonine kinase 1(AKT1), tumor necrosis factor(TNF), and epidermal growth factor receptor(EGFR). The KEGG enrichment analysis showed that non-polysaccharide fraction of Bletillae Rhizoma mainly exerted the therapeutic effect by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT) signaling pathway, mitogen-activated protein kinase(MAPK) signaling pathway, and Ras signaling pathway. The results of animal experiments showed that non-polysaccharide fraction of Bletillae Rhizoma could significantly improve alcohol-induced ulceration in mice to increase ulcer inhibition rate, decrease the levels of TNF-α, interleukin(IL)-1β, IL-6, vasoactive intestinal peptide(VIP), and thromboxane B2(TXB2), elevated the le-vels of IL-10, prostaglandin E2(PGE2), epidermal growth factor(EGF), and vascular endothelial growth factor(VEGF), down-re-gulate the protein levels of PI3K and AKT, and up-regulate the protein levels of p-PI3K and p-AKT. This study indicates that Bletillae Rhizoma may play a role in the treatment of gastric ulcer through multiple components, targets, and pathways and verifies partial prediction results of network pharmacology. The findings of this study provide a scientific and experimental basis for clinical application.

Investigating the Protective Effect of Leaves of Calotropis procera (Aiton) for In-vivo Anti-oxidant and Antiulcer Activity using Pylorus Ligation Method

Background: Calotropis procera (Aiton) (Apocynaceae) is a traditional Indian medicinal plant and used in folk medicine for the past decade for the treatment of gastrointestinal disorders. Therefore the current investigation was undertaken to explore the gastroprotective effect of C. procera (Aiton) leaves extract using pylorus ligation-induced gastric ulcer in rats. Methods: The crude powder material was successively extracted with different solvents and concentrated at reduced pressure in a rotary evaporator. The current investigation was carried out by a pylorus ligation-induced gastric ulcer model in rats. Omeprazole, 20 mg/kg and 100, 250, and 500 mg/kg ethanol extract of C. procera (Aiton) leaves were administered orally for 15 consecutive days, on the last day six hours after pylorus ligation animals were sacrificed and the amount of gastric juice, pH, total and free acidity, ulcer index, and pro-inflammatory cytokines along with antioxidant parameters and total protein were also studied. Results: Pretreatment of C. procera (Aiton) leaf extract at the doses 250 and 500 mg/kg, significantly (p < 0.001) decrease the volume of gastric juice, free and total acidity as well as gastric lesions, and secretion of pro-inflammatory cytokine. On the other hand, the pH of gastric juice, mucin content, and total protein was also significantly decreased. Moreover, pretreatment of C. procera (Aiton) significantly (p < 0.001) boost the enzymatic activity and level of different antioxidant markers and attenuated the pylorus ligation-induced level of MDA (p < 0.05) in experimental animals. Conclusion: From this study, it is concluded that the ethanol leaf extract of C. procera (Aiton) extract possess considerable antiulcer and antioxidant potential. For further research findings, it is necessary to explore the mechanism of action for anti-ulcer activity.

Gastroprotective effects of Pikad Tri-phol-sa-mut-than herbal remedy on multiple gastric ulcer models in rats

In Thai traditional medicine, Pikad Tri-phol-sa-mut-than has long been used to alleviate gastrointestinal symptoms, renal disease, inflammation-related disorders, and severe malady. This recipe is composed of dried fruits of Morinda citrifolia L., Coriandrum sativum L., and Aegle marmelos (L.) Corrêa. The aim of this study was to assess the anti-gastric ulcer property of the water extract of Pikad Tri-phol-sa-mut-than (TS), using various animal models with different inducers, including restraint water immersion stress, indomethacin, and ethanol/hydrochloric acid (EtOH/HCl). Its mechanisms of anti-gastric ulcer actions were also elucidated using both in vitro and in vivo experiments. When compared with the control groups, the oral pretreatment of TS at the doses of 150, 300 and 600 mg/kg significantly reduced the gastric ulcer formation in all models. It was also found that TS at the dose of 600 mg/kg could increase gastric wall mucus in rats but could not produce the significant reduction of the gastric volume or total acidity of gastric content. Results from hematoxylin and eosin (H&E) and Periodic acid-Schiff (PAS) staining examinations of gastric tissues confirmed that TS visibly reduced gastric mucosal damage, while immunohistochemistry revealed that TS remarkably suppressed the protein expression of Bcl-2-associated X (BAX), a regulator of apoptosis, compared to those of the control group. The DPPH, ABTS, and FRAP assays showed antioxidant effects of TS. All of these findings demonstrated that TS has gastroprotective effects, which may be related to the increase in the gastric wall mucus secretion, not anti-secretory activity, as well as its antioxidant and antiapoptotic activities.

Liquid-like Oral Sustained-Release System Based on Acid-Sensitive in situ Hydrogel for Alleviate Gastrointestinal Side Effects of Indobufen

Commonly, most oral non-steroidal anti-inflammatory drugs (NSAIDs) have known gastric adverse reactions due to their long-term and high dose administration. In this study, a novel liquid sustained-release system based on multiple-unit in situ hydrogel beads was designed to address this issue. The system is composed of sodium alginate (SA), gellan gum (GG), zinc oxide (ZnO), and magnesium oxide (MgO). Furthermore, indobufen was loaded into the system to evaluate its gastric mucosal protection effect. This effect can be attributed to the topical antacid, pepsin inhibition, and sustained drug release properties of the system. It was proven that the stored solid gel system could undergo a “solid to liquid” transition after shaking. Once swallowed, the liquid gel could disperse well in the stomach as hydrogel beads. Then, the “liquid to solid” gelation occurred from the exterior to interior of each multiple-unit gel bead, triggered by the release of Zn2+ and Mg2+ from neutralization reactions. The formed gel demonstrated mild antacid effect that lasted for 3 hours and 66.3% pepsin inhibition in vivo. Moreover, the rats treated with the indobufen gel system showed a drug plasma concentration versus time curve with less fluctuation compared to the rats treated with the marketed preparation (YinDuo®) group. The gel system also exhibited an extended Tmax (6.50 hours) and reduced Cmax (52.87 μg/mL). Additionally, the gastric mucosal protection of the gel system was verified using three types of peptic gastric ulcer models. These findings suggested that this multiple-unit in situ gel could be a potential oral liquid sustained release delivery system for NSAIDs.

Gastroprotective effect of the flavonoid fustin isolated from Cotinus coggygria heartwood in a rat model of indomethacin-induced gastric ulceration

Abstract Gastric ulcer is a common health issue. Cotinus coggygria heartwood extracts rich in the flavonoids fustin and sulfuretin have shown protective effects in a rat model of indomethacin-induced gastric ulceration. Fustin itself has been protective in a rat model of ethanol-induced gastric ulcer. In the present study we aimed to reveal the effect of the flavonoid fustin isolated from Cotinus coggygria heartwood in a rat model of indomethacin-induced gastric ulceration. Fustin was isolated from Cotinus coggygria heartwood and purified. The experiment was performed on 30 male Wistar rats allocated to three groups – Control, Indo and F10. F10 group was pretreated with fustin (10 mg/kg b.w. for 7 days). Rats were sacrificed and macroscopic, histopathological and immunohistochemical investigations of the stomachs were performed. Indomethacin caused severe mucosal damage, proven by the macroscopic, microscopic and immunohistochemical gastric mucosa investigation. Fustin pretreatment slightly reduced the macroscopic indices for gastric damage (ulcer number, area, score and index), and significantly alleviated the severity of the microscopic indices (mucosal erosions, necrosis, hemorrhages and inflammation). In fustin-pretreated rats, the expression of NF-κB was reduced in comparison with indomethacin-treated animals. In conclusion, fustin exerted a gastroprotective action in an indomethacin-induced gastric ulceration model, probably due to its anti-inflammatory activity.

Anti-Inflammatory, Antinociceptive, Antipyretic, and Gastroprotective Effects of Eurycoma longifolia Jack Ethanolic Extract.

Tongkat ali (Eurycoma longifolia Jack) (ELJ) is a plant in the Simaroubaceae family. Its roots are used in traditional Thai medicine to treat inflammation, pain, and fever; however, the antiulcer abilities of its ethanolic extract have not been studied. This study examined the anti-inflammatory, antinociceptive, antipyretic, and gastroprotective effects of ethanolic ELJ extract in animal models and found that ELJ effectively reduced EPP-induced ear edema in a dose-dependent manner and that a high dose of ELJ inhibited carrageenan-induced hind paw edema formation. In cotton-pellet-induced granuloma formation, a high dose of ELJ suppressed the increases in wet granuloma weight but not dry or transudative weight. In the formalin-induced nociception study, ELJ had a significant dose-dependent inhibitory impact. Additionally, the study found that yeast-induced hyperthermia could be significantly reduced by antipyretic action at the highest dose of ELJ. In all the gastric ulcer models induced by chemical substances or physical activity, ELJ extracts at 150, 300, and 600 mg/kg also effectively prevented gastric ulcer formation. In the pyloric ligation model, however, the effects of ELJ extract on gastric volume, gastric pH, and total acidity were statistically insignificant. These findings support the current widespread use of Eurycoma longifolia Jack in traditional medicine, suggest the plant's medicinal potential for development of phytomedicines with anti-inflammatory, antinociceptive, and antipyretic properties, and support its use in the treatment of gastric ulcers due to its gastroprotective properties.

Gastroprotective effect of sumatriptan against indomethacin-, stress- and ethanol-induced gastric damage in male rats: Possible modulatory role of 5-hydroxytryptamine 1B/1D receptors and pro-inflammatory cytokines.

The current study was aimed to investigate the beneficial effect of sumatriptan, a 5-hydroxytryptamine 1B/1D (5HT1B/1D ) receptor agonist, on gastric ulcer in rats via stimulating 5HT1B/1D receptors and suppressing pro-inflammatory cytokines. Rats were allocated into three models of gastric ulcer: indomethacin (30 mg/kg, PO), water immersion restraint stress (WRS) and ethanol (5ml/kg PO). Animals were administered with sumatriptan (0.01, 0.1, 0.3 and 1mg/kg, i.p) 30 min before gastric ulcer induction. GR-127935 (0.01 mg/kg, i.p, a selective 5HT1B/1D antagonist) was administered 30 min before sumatriptan (0.1mg/kg) injection. Macroscopic assessments (J-score), ELISA analysis of tumour necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) and histopathological changes were performed on the rat's stomach tissues. Gastric ulcer induction in three models caused an increase in J-score, TNF-α, IL-1β and microscopic features. Sumatriptan (0.1mg/kg) significantly improved gastric injury induced by indomethacin, WRS and ethanol through the reduction in the J-score, TNF-α, IL-1β and microscopic lesions. Concurrent administration of GR-127935 (0.01 mg/kg) with sumatriptan (0.1mg/kg) reversed the gastroprotective effect of sumatriptan in three models. Sumatriptan possessed gastroprotective effects on indomethacin-, WRS- and ethanol-induced gastric damage in rats via the possible involvement of the 5HT1B/1D receptors.

Evaluation of the gastroprotective and ulcer healing properties by Fridericia chica (Bonpl.) L.G. Lohmann hydroethanolic extract of leaves.

Fridericia chica (Bonpl.) L.G. Lohmann (Bignoniaceae), is a climber native to Brazil, found in all Brazilian biomes. It is mostly known in Brazil as "carajiru," and home medicines made from the leaves have been used to cure disorders including stomach ulcers and other gastrointestinal disorders. The objective of the study was to investigate the F. chica hydroethanolic extract of leaves (HEFc) preventative and curative antiulcer gastrointestinal efficacy as well as the mechanisms of action using in vivo rodent models. F. chica was collected in the municipality of Juína, Mato Grosso, and its leaves were used to prepare the extract by maceration technique (70% hydroethanol in the 1:10 ratio, w/v) to obtain the HEFc. The chromatographic analysis of HEFc was carried out by High Performance Liquid Chromatography-Photo Diode Array-Electrospray Ionization-Mass Spectrometry (HPLC-PDA-ESI-MS)- LCQ Fleet™ system. To determine the potential antiulcer potential of HEFc (1, 5 and 20mg/kg, p.o.), the gastroprotective activity was assessed in various animal models of stomach ulcers caused by acidified ethanol, water constraint stress, indomethacin, (acute), and acid acetic (chronic). Additionally, the prokinetic properties of the HEFC were assessed in mice. The gastroprotective underlying mechanisms were evaluated by the histopathological analysis and determination of gastric secretion (volume, free and total acidity), gastric barrier mucus, activation of PGs, NO, K+ATP channels, α2-adrenoceptor, antioxidant activity (GSH, MPO and MDA), NO and mucosal cytokines (TNF-α, IL-1β, and IL-10) levels. The chemical composition of HEFc was analyzed and apigenin, scutellarin, and carajurone were identified. HEFc (1, 5 and 20mg/kg) showed effect against acute ulcers induced by HCl/EtOH with a reduction in the ulcerated area of 64.41% (p<0.001), 54.23% (p<0.01), 38.71% (p<0.01), respectively. In the indomethacin experiment, there was no change in the doses tested, whereas in the water immersion restraint stress ulcer there was a reduction of lesions at doses of 1, 5, and 20mg/kg by 80.34% (p<0.001), 68.46% (p<0.01) and 52.04% (p<0.01). HEFc increased the mucus production at doses of 1 and 20mg/kg in 28.14% (p<0.05) and 38.36% (p<0.01), respectively. In the pyloric ligation-induced model of gastric ulceration, the HEFc decreased the total acidity in all doses by 54.23%, 65.08%, and 44.40% (p<0.05) and gastric secretory volume in 38.47% at dose of 1mg/kg (p<0,05) and increased the free acidity at the dose of 5mg/kg by 11.86% (p<0.05). The administration of EHFc (1mg/kg) showed a gastroprotective effect possibly by stimulating the release of prostaglandins and activating K+ATP channels and α2-adrenoreceptors. Also, the gastroprotective effect of HEFc involved an increase in CAT and GSH activities, and a reduction in MPO activity and MDA levels. In the chronic gastric ulcer model, the HEFc (1, 5 and 20mg/kg) decreased the ulcerated area significantly (p<0.001) at all doses by 71.37%, 91.00%, and 93.46%, respectively. In the histological analysis, HEFc promoted the healing of gastric lesions by stimulating the formation of granulation tissue and consequently epithelialization. On the other hand, regarding the effect of HEFc on gastric emptying and intestinal transit, it was observed that the extract did not alter gastric emptying, but there was an increase in intestinal transit at the dose of 1mg/kg (p<0.01). These outcomes confirmed the advantages of Fridericia chica leaves for the treatment of stomach ulcers, which are well-known. HEFc was discovered to have antiulcer characteristics through multitarget pathways, which might be related to an increase in stomach defense mechanisms and a decrease in defensive factor. HEFc can be regarded as a potential new antiulcer herbal remedy because of its antiulcer properties, which may be attributed to the mixture of flavonoids, apigenin, scutellarin and carajurone.

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

Gastroprotective Effects of the Combination of Chromolaena odorata L. and Pachyrhizus erosus L. Extracts on Rats with Gastric Ulcer Model

Gastroprotective effects are caused by compounds that can protect the gastric mucosa. Gastroprotective activity provided by plants is due to the presence of a group of secondary metabolite compounds found in the plants. The types of secondary metabolite compounds are flavonoids, tannins, alkaloids and saponins. Chromolaena odorata L. contains tannins, phenols, flavonoids, saponins and steroids, while Pachyrhizus erosus L. is known to contain flavonoids and saponins. This study aimed to determine the gasprotective activity of the combination of Chromolaena odorata L. and Pachyrhizus erosus L. extracts in ethanol-induced rats by observing the parameters of the number of peptic ulcers, protection ratio, and images of gastric histopathology. The research method was to make a combination of Chromolaena odorata L. and Pachyrhizus erosus L. extracts which were given to six treatment groups: normal group without treatment; negative control group; positive control group given sucralfate; and three groups given a combination treatment of Chromolaena odorata L. and Pachyrhizus erosus L. extract with a dose of 100, 200, and 400 mg/kgBW. Treatment was done by oral administration for 14 days. On Day 14, after one hour of treatment, 96% ethanol induction was given orally at a dose of 2 ml/200 gBW except for the normal group. The ulcer index produced by negative control, positive control, the treatment with doses of 100, 200, and 400 were 4.18; 2.98; 2.49; 1.64; and 0.78, respectively. The combination of Chromolaena odorata L. and Pachyrhizus erosus L. extracts can prevent gastric damage in rats caused by ethanol induction.

The apelin-apela receptor APJ is necessary for formation and healing of ischemia reperfusion-induced gastric ulcer in rats

The apelinergic system widely expressed and regulates hormone-enzyme secretion, motility, and protective mechanisms of the stomach. This system consists of the apelin receptor (APJ) and two peptides known as apela and apelin. The IR-induced experimental gastric ulcer model is a well-known and commonly used one that induces hypoxia and causes the release of proinflammatory cytokines. Expressions of apelin and its receptor APJ are induced by hypoxia and inflammation in the gastrointestinal tract. Apelin has been shown to affect angiogenesis positively, considered the most critical component of the healing process. Although it is known that apelin and AJP expressions are induced by inflammatory stimuli and hypoxia, stimulate endothelial cell proliferation and have a role in regenerative angiogenesis, no information or has been found in the literature regarding the role of APJ in the formation and healing of gastric mucosal lesions induced by I/R. So, we conducted a study to clarify the role of APJ in formation and healing mechanisms of IR-induced gastric lesions. Male Wistar rats were divided into five groups; control, sham-operated, IR, APJ antagonist treated-IR group (F13A+IR), and the healing groups. F13A was intravenously given to the animals. Gastric lesion index, mucosal blood flow, PGE2, NOx, 4-HNE-MDA, HO activity, and protein expressions of VEGF and HO-1 were measured. F13A application before the IR increased the mucosal injury, F13A application following the ischemia delayed the mucosal healing during the reperfusion period. Consequently, blocking apelin receptors may worsen gastric injury due to the IR and delay mucosal healing.

Involvement of sympathetic nerve activation in acupoint application induced improvement of gastric ulcer and motility in rats with gastric ulcer

To observe the effect of mustard oil application at "Liangmen" (ST21) on gastric ulcer (GU) and gastric motility and its association with the sympathetic nerve activity in rats with GU, so as to provide experimental basis for improvement of GU by acupoint application. Thirty-nine male SD rats were randomly divided into control (n=7), model, acupoint application (AA), medication (guanethidine, an adrenergic sympathetic antagonist) and AA+medication groups (n=8 in each of the latter 4 groups). The GU model was made by applying acetic acid-immersed filter paper onto the gastric antrum. For rats of the AA and AA+medication groups, 50% mustard oil was applied to left ST21 for 10 min, once a day, for 9 consecutive days. Rats of the medication and AA+medication groups received intraperitoneal injection of guanethidine solution (40 mg/kg) beginning from the modeling day on, once a day for 10 consecutive days. The rat's body weight of each group was recorded on the 0th, 1st, 3rd, 7th and 9th day. The intragastric peristaltic wave frequency and the myoelectrical activity (frequency of slow waves, and integration of fast waves) of the gastric smooth muscle were recorded by using PowerLab data acquisition system. The gastric ulcer area was measured after the rats were executed, and histopathological changes of gastric antrum tissues (histopathological score including epithelial cell injury, submucosal edema, hemorrhagic injury, inflammatory cell infiltration score) were observed after H.E. staining. Compared with the control group, the body weight ratio, frequency of gastric peristaltic waves and slow wave frequency of gastric smooth muscle were significantly decreased (P<0.001, P<0.05), while the ulcer area, total histopathological score, epithelial cell injury score, submucosal edema score, hemorrhagic injury score and inflammatory cell infiltration score were significantly increased in the model group (P<0.05, P<0.001). Relevant to the model group, the AA group had a significant increase in the body weight ratio, frequency of gastric peristaltic waves, slow wave frequency, integration of fast waves (P<0.05, P<0.001), and a considerable decrease in the ulcer area, total histopathological score, epithelial cell injury score, submucosal edema score, hemorrhagic injury score and inflammatory cell infiltration score (P<0.05, P<0.001), and the medication group has a significantly decrease in the frequency of gastric peristaltic waves (P<0.05). In comparison with the AA group, the body weight ratio, frequency of gastric peristaltic waves and slow wave frequency of gastric smooth muscle in both medication and AA+medication groups, and the integration of fast waves in the medication group were obviously lower (P<0.05, P<0.001, P<0.01), whereas the levels of ulcer area, total pathological score, submucosal edema score, hemorrhagic injury score and inflammatory cell infiltration score in both medication and AA+medication groups, and the epithelial cell injury score in medication group were significantly higher (P<0.05, P<0.001). Application of mustard oil at acupoint ST21 can effectively remit GU caused by acetic acid and regulate gastric rhythmic contraction, which was mediated by sympathetic nerve.

Omeprazole and H2S releasing agents encapsulated in chitosan nanoparticles to enhance healing process against indomethacin-induced gastric ulcer model

Omeprazole and H2S releasing agents encapsulated in chitosan nanoparticles to enhance healing process against indomethacin-induced gastric ulcer model

Gastroprotective and Curative Effects of the Aqueous Extract of Stem Bark of Pittosporum Mannii Hook F. (Pittosporaceae) on Some Models of Gastric Ulcer in Rats

Purpose: This work assesses the antiulcerogenic and antiulcer properties of the aqueous extract of Pittosporum mannii and shows at what dosage this plant would not be of any danger to the patient.&#x0D; Methodology: The aqueous extract of its bark, orally administered at the doses of 35, 75, 150 and 300mg/kg, has been experimented on acute (HCl/EtOH (150mM HCl in 60% ethanol); ligature of the pylorus) and chronic ulcers (acetic acid; 0.05 ml of 30% acetic acid) induced on rats.&#x0D; Findings: The results from these experiments show that: the aqueous extract of the barks of Pittosporum mannii possesses antiulcerogenic properties. At 300mg/kg dose, the extract completely inhibited (100%) the ulcer induced by the mixture HCl/EtOH. For the three patterns of gastric ulcers induction used, the mucus weight did not vary significantly (p&gt;0.05) on the treated animals as compared to the negative control groups. In the group that underwent pylorus ligature, the extract did not induce any significant variation in both the gastric acidity and the gastric volume. However these results do not bring out the exact mechanism of action of the plant extract. Furthermore, the extract neither acts in reinforcing the protection barrier of the gastric mucus membrane nor its antisecretory properties. The nitric oxide proportion of the gastric mucous membrane presents a significant variation (p&lt;0.05) at the dose of 300mg/kg. With regards to these results, we realized that this extract increases the nitric oxide rate of the gastric mucosa which intervenes in the healing process. The aqueous extract of the stem bark of Pittosporum mannii provokes the death of all animals of the groups from a dose of 3g/kg (LD100) whereas half of the population of the experimental rats succumbed at the dose of 2.66g/kg (LD50). After two weeks of treatment, the rats that received the extract at the doses of 75, 150 and 300mg/kg presented no significant variation of the hepatic and plasmatic protein levels. The levels of plasma transaminases (AST; 300mg/kg), hepatic ALT (300mg/kg) and plasmatic ALT (150mg/kg) present a significant drop. The stem bark of Pittosporum mannii possess gastroprotective and ulcer-healing effect although at this time it is difficult to explain the exact mechanism involved in these two processes.&#x0D; Unique contribution to theory, policy and practice: According to the results obtained, it would be important to realise a histological test of the detoxification organs such as the liver, the heart and the kidneys. Moreover, the cytotoxicity test has to be done to determine the effect of the extract at the cellular level before any therapeutic use

ALDH2 ameliorates ethanol-induced gastric ulcer through suppressing NLPR3 inflammasome activation and ferroptosis

Gastric ulcer (GU) is a prevalent and life-threating gastrointestinal disorder. Aldehyde dehydrogenase 2 (ALDH2) is a pivotal component of alcohol metabolism which has been supported to suppress oxidative stress-elicited DNA damage in gastric mucosa cells. Nonetheless, whether ALDH2 is also involved in GU remains indistinct. Firstly, HCl/ethanol-induced experimental rat GU model was successfully established. RT-qPCR and Western blot tested ALDH2 expression in rat tissues. Following the addition of ALDH2 activator Alda-1, gastric lesion area and index were measured. H&E staining detected the histopathology of gastric tissues. ELISA examined the levels of inflammatory mediators. Alcian blue staining evaluated mucus production of gastric mucosa. Oxidative stress levels were estimated by corresponding kits and Western blot. Western blot examined the expression of NLRP3 inflammasome- and ferroptosis-related proteins. Prussian blue staining and corresponding assay kits measured ferroptosis. In ethanol-treated GES-1 cells, NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, iron content, ferroptosis, inflammation and oxidative stress were detected as aforementioned above. In addition to that, DCFH-DA staining examined ROS generation. The experimental data corroborated that ALDH2 expression was declined in the tissues of HCl/ethanol-treated rats. Alda-1 ameliorated HCl/ethanol-stimulated gastric mucosal damage, inflammatory response, oxidative stress, NLRP3 inflammasome activation and ferroptosis in rats. Also, the suppressive role of ALDH2 in inflammatory response and oxidative stress was reversed by ferroptosis activator erastin or NLRP3 activator nigericin in HCl/ethanol-challenged GES-1 cells. To be summarized, ALDH2 might play the protective role in the process of GU.

Gastroprotective effects of bromelain on indomethacin-induced gastric ulcer in rats

Gastric ulcer is one of the most common diseases of the gastrointestinal system and some of its complications are the main causes of morbidity and mortality. Bromelain (BRM), a sulfhydryl proteolytic enzyme, has multiple activities in many areas of medicine as an antioxidant and anti-inflammatory agent. In this study, it was aimed to investigate the anti-inflammatory and oxidative stress-mediated therapeutic effect of BRM in a gastric ulcer model induced by indomethacin (IND) which is a non-steroidal anti-inflammatory drug (NSAID) with gastric ulcer-forming effects. Gastric mucosal paraoxonase (PON), arylesterase (ARE), catalase (CAT), myeloperoxidase (MPO) and glutathione peroxidase (GPx) activity and total glutathione (GSH) levels were analyzed. Interleukin-33 (IL-33), the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) levels were determined by immunohistochemically. Although IND-induced histopathological changes occurred, BRM pretreatment prevented these effects. As a result of the study, it was determined that BRM had an anti-ulcerative effect at a dose of 50 mg/kg. BRM given at this dose significantly decreased gastric tissue MPO activity, and increased CAT, PON, ARE, GPx activity and GSH level. The increased IL-33 and decreased Nrf-2 and HO-1 levels were obtained in IND group and these changes were reversed by BRM. As a result, it was concluded that BRM may have protective effects in IND-induced gastric model by reducing inflammation and regulating oxidant/antioxidant balance.

Gastroprotective effect of Artemisia absinthium L.: A medicinal plant used in the treatment of digestive disorders

Ethnopharmacological relevanceWormwood (Artemisia absinthium L.) is traditionally used for stomach pain and gastric relief. However, its possible gastroprotective effect has not yet been experimentally evaluated. Aim of the studyThis study evaluated the gastroprotective effect of aqueous extracts obtained through hot and room temperature maceration of A. absinthium aerial parts in rats. Materials and methodsThe gastroprotective effect of hot aqueous extract (HAE) and room temperature aqueous extract (RTAE) from A. absinthium aerial parts were evaluated in rats using a model of acute gastric ulcer induced by ethanol p.a. The stomachs were collected to measure the gastric lesion area and histological and biochemical analysis. UHPLC-HRMS/MS analysis was used to determine the chemical profile of the extracts. ResultsEight main peaks in the UHPLC chromatogram were identified in both HAE and RTAE extracts: tuberonic acid glycoside (1), rupicolin (2), 2-hydroxyeupatolide (3), yangabin (4), sesartemin (5), artemetin (6), isoalantodiene (7), and dehydroartemorin (8). For RTAE, a higher diversity of sesquiterpene lactones was observed. The groups treated with RTAE at 3%, 10%, and 30% presented a gastroprotective effect, reducing the lesion area by 64.68%, 53.71%, and 90.04%, respectively, when compared with the vehicle (VEH)-treated group. On the other hand, the groups treated with HAE at 3%, 10%, and 30% presented values of lesion areas higher than those of the VEH group. Changes in the submucosa layer, inflammatory process with edema, cellular infiltration, and mucin depletion were detected in the gastric mucosa exposed to ethanol, which was fully prevented by RTAE treatment. Neither HAE nor RTAE could increase the reduced glutathione levels in the injured gastric tissue, but RTAE (30%) reduced the formation of lipid hydroperoxides. When the rats were pre-treated with NEM (a chelator of non-protein thiols) or L-NAME (non-selective nitric oxide synthase inhibitor), the RTAE lost the ability to protect the gastric mucosa. ConclusionsThis study corroborates the ethnopharmacological use of this specie to treat gastric disorders revealing the gastroprotective effect of the room-temperature aqueous extract of A. absinthium aerial parts. Its mode of action may involve the ability of the infusion to maintain the gastric mucosal barrier integrity.

Pumpkin Oil-Based Nanostructured Lipid Carrier System for Antiulcer Effect in NSAID-Induced Gastric Ulcer Model in Rats [Retraction

[This retracts the article DOI: 10.2147/IJN.S247252.].