Gastric Ulcer Model Research Articles

Gastroprotective Effect of Chinese Cabbage (Brassica oleracea L. var. pekinensis) Juice in Sprague Dawley Rats

Background: Chinese cabbage or Brassica oleracea L. var. pekinensis is an edible leafy green vegetable in the family of Brassicaceae. Ethnopharmacological studies have shown that the juice of cabbage leaves is commonly used in the treatment of gastrointestinal disorders, irritable bowel syndrome, minor cuts and wounds and mastitis. Objective: This study was aimed to examine the gastroprotective effect of Chinese cabbage (Family: Brassicaceae) juice in rats by using ethanol-induced gastric ulcer model. Methods: Thirty albino male Sprague Dawley rats (150 ± 20 g) were divided into 6 groups with five rats (n = 5) in each group. The normal control group was treated with distilled water while the positive control group was intragastrically administered with omeprazole (20 mg/kg). Cabbage juice at 500 mg/kg was given orally to three experimental groups for 1-day, 7-day and 14-day, respectively. Ethanol (70 % v/v) was orally treated to all rats one hour after the last dose treatment except the normal control group. Results: Results obtained showed that repeated consumption of cabbage juice for 7 days and 14 days exhibited an increase in accumulation mucus and in the levels of superoxide dismutase (SOD), glutathione- s-transferase (GST) and glutathione peroxidase (GSH-Px) as well as a reduction in gastric lesion area induced by ethanol compared with the ulceration control group. Conclusion: In conclusion, the gastroprotective effect of Chinese cabbage juice could be associated with its ability to increase endogenous antioxidant activities of SOD, GST and GSH-Px and mucus secretion in rat stomach.

Research on the protection and mechanism of coptis alkaloids on acetic acid type gastric ulcer

This paper studied the therapeutic effect of Coptis alkaloids on acetic acid type gastric ulcer and its possible mechanism. Acetic acid type gastric ulcer model is used and administered for 7 days, and the rats are killed, and then IPP software is used to calculate the area of ulcer of gastric tissue and the inhibition rate of ulcer. ELISA kit is also used to measure the expression level of epidermal growth factor (EGF) in serum of rats, 5-hydroxytryptamine (5-HT) in brain and noradrenaline (NE) in adrenal tissue. At the same time, HE staining is used to observe the healing state of gastric tissue. The experiment result shows that the ulcer area of Coptis total alkaloids group 25 mg/kg/day is significantly lower than that of the model group (P < 0.01), and the inhibition rate of ulcer is more than 50%; at the same time, it increases the content of EGF in serum (P < 0.05), promotes the healing of injured gastric tissue; and it also significantly increases 5-HT content in brain tissue and NE content in adrenal tissue (P < 0.01, P < 0.01), and to some extent, it regulates the mood of rats and prevents the recurrence of ulcer; the HE staining results shows that the Coptis total alkaloids promotes the recovery of gastric injury. Therefore, the Coptis total alkaloids can promote the healing of acetic acid type gastric ulcer, and its mechanism may be that it improves the healing quality of gastric ulcer by regulating the emotion of rats, which results in the effect of treating gastric ulcer.

Chemical profile and gastroprotective effect of Jatropha elliptica (Pohl) Oken roots

Jatropha elliptica (Pohl) Oken (Euphorbiaceae) roots are used in folk medicine to treat gastric ulcers. The purpose of this work was to evaluate the gastroprotective activity of ethanol extract (JER) and hexane fraction (ERH) of J. elliptica roots in mice, as well as to analyze the acute toxicity of the extract and identify the potential active compounds. No signs of toxicity were observed in JER. In both acidified ethanol and indometacin-induced gastric ulcer models, all doses tested of JER and ERH significantly reduced gastric lesions. Dereplication of JER was performed by HPLC-DAD-ESI-MS/MS and resulted in the annotation of compounds fraxetin, propacin, jatrophone and jatropholones A and B. GC–MS analysis of ERH revealed the diterpenes jatrophone, jatropholone A and jatropholone B as the major components. The chemical study of this fraction has led to the isolation of these compounds, in addition to the sequiterpene cyperenoic acid and the diterpene 2β-hydroxyjatrophone, both reported for the first time in J. elliptica. The isolated compounds were tested against L929 cells and only cyperenoic acid and the mixture of jatropholones A and B did not show toxicity, being then selected as good candidates for bioassays using acidified ethanol-induced gastric ulcer model. Cyperenoic acid significantly decreased gastric lesions and preserved gastric mucus layer. The mixture of jatropholones A and B caused a smaller reduction of gastric lesions, without preservation of the gastric mucus layer. The study showed that J. elliptica roots present gastroprotective activity in mice, without causing acute toxic effects. The activity is related, at least in part, to the occurrence of terpenes, mainly the sesquiterpene cyperenoic acid.

Anti-ulcer activity of methanol extract of the leaves of Hannoa klaineana in rats

Ulcer is a common gastrointestinal disease affecting 5% of the world’s population. Hannoa klaineana is used locally in the management of many gastrointestinal disorders and fevers. The study was conducted to evaluate toxicity profile and anti-ulcer effect of methanol extract of the leaves of Hannoa klaineana (Simaroubaceae). Acute toxicity test was conducted according to OECD guideline 423 using the limit test dose (5000 mg/kg) for 14 days. Sub-chronic toxicity study was carryout according to OECD guideline 407 by daily oral administration of the extract (500 and 1000 mg/kg) for 28 days. Anti-ulcer effect of the extract (100, 200 and 400 mg/kg b.wt) was evaluated using ethanol and indomethacin induced gastric ulcer models. In acute toxicity test, 5000 mg/kg dose of the extract does not caused mortality nor any sign of toxicity observed in the rats, thus, the LD50 value of the extract was above 5000 mg/kg. While sub-chronic toxicity test, the extract demonstrated significant (p&lt;0.01) increase in body weight and weight of the liver, spleen and kidneys of the rats. The result also showed significant (p&lt;0.05) dose-dependent decrease in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea, uric acid and creatinine. Ethanol-induced ulcer model, the extract demonstrated significant (p&lt;0.05) dose-dependent decrease in mean ulcer index, with percentage inhibition (62.84%) of gastric damage at 400 mg/kg. While indomethacin model, the extract exhibited significant (p&lt;0.001) dosedependent decrease in mean ulcer index with percentage gastroprotection (99.20%) at 400 mg/kg. This study suggested that methanol extract of the leaves of Hannoa klaineana is safe for oral administration and exhibited strong anti-ulcer effect, thus validating the traditional use of the plant leaves in ulcer treatment.

Can aprepitant used for nausea and vomiting be good gastrointestinal complaints?

Aprepitant is a selective SP/NK-1 receptor antagonist and used in postoperative and chemotherapeutics induced emesis and vomiting. The aim of our study is to show aprepitant may have beneficial effects on gastrointestinal complaints in cancer patients undergoing chemotherapeutics by indomethacin-induced gastric ulcer model. A total of 48 rats were fasted 24h for ulcer experiment. Aprepitant doses of 5, 10, 20, and 40mg/kg were evaluated for their antiulcer activity. Omeprazole (20mg/kg) was used as a positive control group. Six hours after 25mg/kg indomethacin administration, all stomachs were dissected out. After macroscopic analyses, tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), COX-1, and COX-2 mRNA levels and SOD activity, and GSH and MDA levels of stomachs were determined. Histopathological examinations were evaluated. Aprepitant administration exerted 48.14%, 49.62%, 65.92%, and 76.77% ulcer inhibition effects at 5, 10, 20, and 40mg/kg, respectively. Aprepitant administration decreased oxidative stress and inflammatory parameters in stomach tissues dose dependently. Aprepitant administration increased stomach COX-2 mRNA levels at 20 and 40mg/kg doses. Although aprepitant appears to be disadvantageous in terms of treating gastric ulcer due to COX enzyme inhibition according to the previous studies, aprepitant has been shown to have ulcer healing effect in our study. When aprepitant is given as an anti-nausea and vomiting drug to cancer patients undergoing chemotherapy, we can argue that it will not be necessary to add a new gastric protective agent as it also shows beneficial effects in gastrointestinal complaints.

Synthesis of Hydroxybenzofuranyl-pyrazolyl and Hydroxyphenyl-pyrazolyl Chalcones and Their Corresponding Pyrazoline Derivatives as COX Inhibitors, Anti-inflammatory and Gastroprotective Agents.

Five new series of hydroxybenzofuranyl-pyrazolyl chalcones 3a,b, hydroxyphenyl-pyrazolyl chalcones 6a-c and their corresponding pyrazolylpyrazolines 4a, d, 7a-c and 8a-f have been synthesized and evaluated for their in vitro cyclooxygenase (COX)-1 and COX-2 inhibitory activity. All the synthesized compounds exhibited dual COX-1 and COX-2 inhibitory activity with obvious selectivity against COX-2. The pyrazolylpyrazolines 4a-d and 8a-f bearing two vicinal aryl moieties in the pyrazoline nucleus showed more selectivity towards COX-2. Within these two series, derivatives 4c, d and 8d-f bearing the benzenesulfonamide group were the most selective. Compounds 4a-d and 8a-f were further subjected to in vivo anti-inflammatory screening, ulcerogenic liability and showed good anti-inflammatory activity with no ulcerogenic effect. In addition compounds 4c and 8d as examples showed prostaglandin (PG)E2 inhibition % 44.23 and 51.4 respectively, tumor necrosis factor α (TNFα) inhibition % 33.48 and 41.41 respectively and gastroprotective effect in ethanol induced rodent gastric ulcer model. In addition, to explore the binding mode and selectivity of our compounds, 8d and celecoxib were docked into the active site of COX-1 and COX-2. It was found that compound 8d exhibited a binding pattern and interactions similar to that of celecoxib with COX-2 active site, while bitter manner of interaction than celecoxib to COX-1 active site.

Estragole prevents gastric ulcers via cytoprotective, antioxidant and immunoregulatory mechanisms in animal models

BackgroundEstragole is an aromatic organic compound belonging to the class of phenylpropanoids derived from cinnamic aldehydes and present in essential oils of plant species, such asRavensara anisata (madeira), Ocimum basilicum (manjericão/alfavaca) and Croton zehntneri (canelinha). Pharmacological studies report its anti-inflammatory, antioxidant and vasorelaxant activity. Hypothesis/PurposeThis study aimed to evaluate the acute non-clinical toxicity, gastroprotective activity and the related mechanisms of action. MethodsAcute toxicity was assessed according to OECD guide 423 in mice. Ethanol, stress, piroxicam and pylorus ligation-induced gastric ulcer models were used to investigate antiulcer properties. The related mechanisms of action were using the ethanol-gastric lesions protocol. ResultsIn the acute oral toxicity assay, doses of 300 or 2000 mg/kg of estragole administered orally in Swiss mice did not induce any behavioral changes. However, the dose of 2000 mg/kg showed a decrease in water and feed intake. Lethal dose 50 % (LD50) was set to be equal to or greater than 2500 mg/kg, according to OECD. In all evaluated protocols, estragole (31.25, 62.5, 125 and 250 mg/kg) significantly reduced the area of ​​ulcerative lesion when compared to control groups. To investigate the mechanisms involved in the gastroprotective activity, the antisecretory or neutralizing of gastric secretion, cytoprotectant, antioxidant and immunoregulatory effects were evaluated. Results showed that treatment with estragole (250 mg/kg) reduced (p < 0.05) the volume of the gastric juice. Besides, sulfhydryl groups, nitric oxide, mucus and prostaglandins seems to be involved in the gastroprotective property. Treatment also increased (p < 0.001) levels of reduced glutathione (GSH), interleukin-10 (IL-10) and positive cells marked for glutathione peroxidase (GPx) and cyclooxygenase 2 (COX-2). It also reduced (p < 0.001) malondialdehyde (MDA), myeloperoxidase (MPO), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and inducible nitric oxide synthase (iNOS) (p < 0.05) levels. ConclusionThus, it is possible to infer that estragole presents gastroprotective activity related to antisecretory, cytoprotective, antioxidant and immunomodulatory mechanisms.

Effects of Paeonol and Gastroretention Tablets of Paeonol on Experimental Gastric Ulcers and Intestinal Flora in Rats.

Paeonol, a major ingredient isolated from Moutan Cort, has various pharmacological effects. Our previous studies have shown that paeonol can exert antioxidant and anti-inflammatory therapeutic effects on ethanol-induced experimental gastric ulcer (GU). Therefore, in this study, we designed two GU models in rats induced by pyloric ligation (PL) and acetic acid and evaluated the protective effects of paeonol and gastroretention tablets of paeonol (GRT-Ps; 24, 48, and 96 mg/kg) on GU in rats and the effect of paeonol (48 mg/kg) on the intestinal flora. In vivo experiments showed that paeonol or GRT-Ps remarkably reduced gastric mucosal damage in a dose-dependent manner in the different types of models and improved the superoxide dismutase (SOD) activity and the malondialdehyde (MDA) content. And in fact, the sustained-release effect of GRT-Ps is more conducive to the improvement of GU compared with the rapid clearance of free drugs. In the PL-induced model, gastric secretion parameters, that is, pH and total acid, showed significant differences compared with the model group. In addition, paeonol treatment can improve the richness and diversity of the intestinal flora and increase the amount of beneficial bacteria, such as Lactobacillus. Paeonol and its stable sustained-release tablet GRT-Ps can promote ulcer healing by inhibiting oxidative stress and regulating the intestinal flora. This study can provide basis for the clinical treatment of GU with paeonol. Graphical Abstract.

Rosmarinic acid prevents gastric ulcers via sulfhydryl groups reinforcement, antioxidant and immunomodulatory effects.

Rosmarinic acid (RA) is a secondary metabolite present in several plant species that has already demonstrated antioxidant, antiallergic, anticancer, antimicrobial, neuroprotective, and hepatoprotective effects experimentally. Due to the promising pharmacological properties found previously, this study aimed to assess the oral acute toxicity and the gastroprotective effect of RA using animal models. Acute toxicity was assessed according to OECD guide 423. Ethanol, stress, NSAIDs, and pylorus ligature-induced gastric ulcer models were used to investigate antiulcer properties. The related mechanisms of action were also evaluated from ethanol-induced gastric lesions protocol. RA (300 and 2000mg/kg) showed no changes in behavioral, water and food intake, body and organs weight parameters with LD50 set around 2500mg/kg. RA presented gastroprotective activity in all assessed doses (25, 50, 100, and 200mg/kg) using different animal models. Besides, it was observed that this effect is not related to the modulation of gastric juice parameters (pH, volume, and [H+]), the participation of nitric oxide, mucus, and prostaglandins. However, increased sulfhydryl groups, GSH and IL-10 levels as well as reduced of proinflammatory cytokine (TNF-α and IL-1β) levels were found for RA-treated groups. RA presents low acute toxicity and gastroprotective activity, preventing ulcer formation via cytoprotective, antioxidant, and anti-inflammatory mechanisms. Graphical abstract.

Cenostigma macrophyllum Tul. var. acuminata Teles Freire Fraction Leaves Stimulate Gastric Healing in Rats and Human Cell Cultures.

Cenostigma macrophyllum Tul. var. acuminata Teles Freire (Leguminosae-Caesalpinioideae) is a medicinal plant traditionally used for treatment of gastric ulcer. This study evaluated the ulcer-healing activity of the hydroalcoholic fraction of C. macrophyllum Tul. var. acuminata Teles Freire leaves (Cm-FHA) and the tea of the leaves of C. macrophyllum (Cm-tea), as well as the possible action of Cm-FHA, through in vitro models. Leaves of C. macrophyllum were dried and powdered to obtain the Cm-FHA. Subsequently, the Cm-FHA was characterized phytochemically and biologically. Besides, Cm-tea was prepared. The gastric healing effects of Cm-tea and Cm-FHA were analyzed using the model of acetic acid-induced gastric ulcer in rats. The human gastric adenocarcinoma (AGS) cell line was employed as an in vitro model. Cm-tea promoted a protective effect against gastric ulcers induced by absolute ethanol. Cm-FHA or Cm-tea (100 mg/kg/7 days) exhibited a significant healing effect on ulcers induced by acetic acid. In the histological analysis, gastric mucosa treated with Cm-FHA or Cm-tea advanced restoration of the mucosal epithelium. In vitro, lower concentrations of Cm-FHA stimulated cell proliferation in the BrdU assay and cell migration. Cm-tea and Cm-FHA present a significant gastric healing effect in in vivo and in vitro models.

Baccharis trimera (carqueja) promotes gastroprotection on ethanol-induced acute gastric ulcer

One of the factors that can promote gastric ulcer is the acute and/or chronic consumption of ethanol. One of the most used therapeutic measures is the use of proton pump inhibitor, like omeprazole. However, these drugs have several side effects, making it necessary to search for new alternatives. To investigate the gastroprotective effect of Baccharis trimera (carqueja) we used an ethanol-induced acute gastric ulcer model. For this, gastric ulcer was induced in rats using absolute ethanol for 2 consecutive days. After analysis of the stomach, an increase in oxidative stress was observed, as well as the reduction of the antioxidant defense. In addition, we observed in histology that there was an increase in inflammatory cells, necrosis, hemorrhage and hyperemia. Treatment with B. trimera was able to decrease oxidative damage as well as improve antioxidant defense. There was also a decrease in inflammation, collagen area and hemorrhage. All the beneficial effects promoted by carqueja were similar to those found by the positive controls used in our study (vitamin C and omeprazole). Analyzing our data, we can conclude that B. trimera presents a gastroprotective effect and should be further studied for its application in gastric ulcer therapy. After 2 days of consumption of absolute ethanol, the animals' stomachs showed an increase in oxidative stress, characterized by reduction of oxidized glutathione (GSSG) and increase of TBARS and carbonylated protein. This situation led to stomach inflammation, necrosis, hemorrhage and hyperemia. These was minimized by the consumption of Baccharis trimera extracts (Bt), since it was able to decrease oxidative damage and increasing GSSG, reduced glutathione (GSH) and catalase (CAT). In addition, there was decreased inflammation, hemorrhage and collagen area after Bt consumption. GR reductase gluthione, GPx peroxidase glutathione. Bt in green: stimulation; Bt in red: inhibits.

LP44 (4-[2-(methylthio)phenyl]-N-(1,2,3,4-tetrahydronaphthalen-1-yl)-1-piperazinehexanamide) exerts anti-ulcer effects via 5-hydroxytryptamine receptor7 activation on indomethacin-induced gastric ulcers in rats.

This study aimed to demonstrate the role of serotonin7 receptor (5-HT7) and the effects of 5-HT7 agonists and antagonists in an indomethacin-induced gastric ulcer. Male albino Wistar rats (n = 60) were used in the experiments. LP44 (5-HT7 agonist) and SB269970 (5-HT7 antagonist) were administered at 10mg/kg as a pre-treatment. One hour after the drug treatments, 25mg/kg of indomethacin (INDO) was administered to all groups except the healthy control group. Six hours after indomethacin administration, all the rats were euthanized. We analyzed the iNOS, eNOS, and 5-HT7 receptor mRNA levels in the stomach tissue of rats by real-time PCR. 5-HT7 mRNA expression was increased in the INDO group compared to the healthy group. LP44 administration exerted a significant upregulatory effect on eNOS mRNA expression and downregulatory effects on iNOS and 5-HT7 mRNA expression compared to the INDO group. However, antagonist (SB269970) administration did not result in such difference in gene expression, but even partially decreased the agonist's effect in combination. Famotidine and agonist exerted similar effects. Histopathological findings supported the beneficial effects of 5-HT7 agonist on gastric tissue. The study suggested that activation of 5-HT7 receptor showed a significant anti-ulcerogenic effect in the indomethacin-induced gastric ulcer model.

Pre-protective effect of polysaccharides purified from Hericium erinaceus against ethanol-induced gastric mucosal injury in rats

The β-glucan H6PC20 (Mw: 2390 kDa) and α-heteropolysaccharide HPB-3 (Mw: 15 kDa) were purified from the fruiting body of Hericium erinaceus according to the previous methods. Their gastroprotective activities and corresponding structure-activity relationship were studied in the ethanol-induced gastric ulcer model of rats. After intragastric administrated with H6PC20 and HPB-3 for 14 days, macroscopic and histological evaluation of gastric mucosa was improved significantly. The defense and repair factors (EGF, bFGF and PGE2) were increased, meanwhile, the inflammatory cytokines (IL-1β and TNF-α) and MDA were reduced. These results indicated that H6PC20 and HPB-3 presented gastroprotective activities with the mechanism of activating repair and defense system, decreasing the inflammatory response and alleviating the oxidative injury. Furthermore, the structure-activity relationship showed that the macromolecular β-glucan was better for repair and defense system, while the low weight molecular α-heteropolysaccharide focused on the anti-inflammatory effect. The polysaccharides purified from H. erinaceus can be developed as a potential gastroprotective ingredient for applications in pharmaceutical field.

Isolation, Gastroprotective Effects and Untargeted Metabolomics Analysis of Lycium Minutifolium J. Remy (Solanaceae).

Lycium minutifolium J. Remy (Solanaceae) is commonly used as an infusion in traditional medicine to treat stomach pain, meteorism, intestinal disorders, stomach ailments, and other severe problems including prostate cancer and stomach cancer. From the EtOAc extract of L. minutifolium bark five known metabolites were isolated using chromatographic techniques. The gastroprotective effects of the EtOAc fraction and edible infusion extract of the bark were assayed on the hydrochloric acid (HCl)/EtOH induced gastric ulcer model in mice to support the traditional use of the plant. The EtOAc extract and the edible infusion showed gastroprotective effect at dose of 100 mg/kg reducing lesions by 31% and 64%, respectively. The gastroprotective action mechanisms of the edible infusion at a single oral dose of 100 mg/kg were evaluated suggesting that prostaglandins, sulfhydryl groups, and nitric oxide are involved in the mode of gastroprotective action. The UHPLC analysis coupled to high-resolution mass spectrometry of the edible infusion showed the presence of twenty-three compounds. Our results can support the gastroprotective properties of the edible infusion extract, and at least can validate in part, the ethnopharmacological uses of the plant.

GASTROPROTECTIVE EFFECT OF SESBANIA GRANDIFLORA LINN. SEEDS EXTRACT.

Background: A peptic ulcer is a sore in the lining of the stomach or the first part of the small intestine. Ulcer can be developed inside the inner lining of the stomach (gastric ulcer) or the small intestine (duodenal ulcer). Peptic ulcers are usually aggravated by an imbalance between destructive and defensive factors in the stomach, it affects nearly 10% of world population. The objective of the study was to investigate the protective effect of ethanolic extract of Sesbania grandiflora Linn. Seeds (SGEE) on peptic ulcer induced by ethanol in experimental rats.&#x0D; Objectives: Gastroprotective effect of Sesbania grandiflora Linn. Seeds extract on experimental&#x0D; Materials and Methods: The gastroprotective effect of SGEE was studied using ethanol (70% ) induced acute gastric ulcer models. The animals were divided into five groups, each group contains six animals. SGEE was administered in two doses, (200 mg/kg and 400 mg/kg, p.o). The parameters investigated include acid volume, pH, total acidity, ulcer index, total protein, glutathione, lipid peroxidase, catalase &amp; histopathological studies.&#x0D; Results: 1. In gastroprotective effect study, SGEE significantly inhibited the development of ulcers induced by ethanol.&#x0D; &#x0D; The SGEE significantly reduced the acid volume, total acidity, total acidity, ulcer index, lipid peroxidation &amp; increases in pH, glutathione &amp; catalase level.&#x0D; Histopathogical studies also revealed that SGEE is gastro-protective. Ranitidine (100 mg/kg) is used as standard drug.&#x0D; &#x0D; Conclusion: All the observation implies that SGEE possess significant protective activity against ethanol induced gastric ulcer in experimental rats. 400 mg/kg doses has shown more protection compared to 200 mg/kg (dose dependent activity was obtained).&#x0D; Keywords: Antiulcer; Sesbania grandiflora; Ethanol; Ranitidine.

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

BackgroundPeptic ulcer disease, a painful lesion of the gastric mucosa, is considered one of the most common gastrointestinal disorders. This study aims to investigate the formulation of pumpkin seed oil (PSO)-based nanostructured lipid carriers (NLCs) to utilize PSO as the liquid lipid component of NLCs and to achieve oil dispersion in the nano-range in the stomach.MethodsBox–Behnken design was utilized to deduce the optimum formula with minimum particle size. The optimized PSO-NLCs formula was investigated for gastric ulcer protective effects in Wistar rats by evaluating ulcer index and determination of gastric mucosa oxidative stress parameters.ResultsPSO was successfully incorporated as the liquid lipid (LL) component of NLCs. The prepared optimum PSO-NLCs formula showed a size of 64.3 nm. Pretreatment of animals using the optimized PSO-NLCs formula showed significantly (p< 0.001) lower ulcer index compared to indomethacin alone group and significantly (p<0.05) less mucosal lesions compared to the raw oil.ConclusionThese results indicated great potential for future application of optimized PSO-NLCs formula for antiulcer effect in non-steroidal anti-inflammatory drug (NSAID)-induced gastric ulcer.

Synthesis and Gastroprotective Evaluation of New Synthetic Indole Imines on Animal Models

The present study was designed to carry out the synthesis of targeted N-arylindole imines (derived from 4,5,6-trimethoxy-2,3-diphenyl-1H-indole-7-carbaldehyde), their characterization by spectroscopic and spectrometric methods, and evaluation of gastroprotector activity. The gastroprotective potential of indole imines (5 – 10) was elucidated after peroral administration of compounds in various doses to h EtOH-induced and indomethacin-induced gastric ulcers. In order to determine the mechanism of drug action, the effects of compounds on pH, ulcer index, gastric volume, gastric mucus content, and antioxidant biomarkers were determined. Among five newly synthesized compounds, two halogen derivatives (8 and 9) showed significant protection at 40 and 60 mg/kg doses as compared to standard drug omeprazole. In EtOH-induced gastric ulcer model, indole imine 9 significantly increased the mucus content. Both compounds (8 and 9) were found to attenuate the formation of gastric lesions in indomethacin-induced ulcer model. The serum values of antioxidant biomarkers revealed promising increase in total antioxidant status by compounds 8 and 9. The obtained results suggest the synthetic indole imines 8 and 9 to be remarkable gastroprotective compounds capable of modulating oxidative stress.

The gastroprotective effects of arrowroot tuber starch (Maranta arundinacea L.) on ethanol-induced gastric damages in rats

Empirically, arrowroot tubers ( Maranta arundinacea L.) have been widely used in the treatment of gastric ulcers. They are known to contain carbohydrates and flavonoids that play a role in reducing inflammation. This study sought to identify the gastroprotective effects of arrowroot tuber starch ( Maranta arundinacea L.) on the ulcer index, % protection ratio, and the histopathological image of Wistar rat models of gastric ulcers. The test animals were divided into six groups. Group I was given free access to food and water (normal control), while Group II was given ethanol without treatment (negative control). Groups III, IV, and V were treated with arrowroot tuber starch at the doses of 125, 250, and 500 mg/kg BW, respectively. Group VI was given sucralfate at the dose of 400 mg/kg BW (positive control). All treatments were administered orally for 14 days and followed by 24 hours of fasting. On Day 15, all groups, except for the normal control, were given 96% ethanol orally at the dose of 1 ml/200gr BW. After one hour, they were dissected, and their stomach was removed for further analyses. The results showed that the administrations of arrowroot tuber starch at 125, 250, and 500 mg/kg BW produced ulcer indices of 2, 1.25, and 1.5, respectively, smaller than the negative control (4.25), and % protection ratios higher than the positive control. The histopathological imaging showed that the stomach of rats receiving arrowroot tuber starch at 250 mg/kg BW presented no pathological changes. Based on these findings, the arrowroot tuber starch is proven to have the ability as a gastroprotective agent.

Preventive effects of Rhizoma Coptidis and Atractylodes on mice with gastric-ulcer.

To detemine preventive effects of compound formula Rhizoma Coptidis and Atractylodes on mice with gastric-ulcer. The mice were randomly divided into a normal group, a gastric ulcer group, a ranitidine positive drug group, a Rhizoma Coptidis group, an Atractylodes group, and a Rhizoma Coptidis plus Atractylodes group (the ratios of Coptidis to Atractylodes were 9꞉1, 8꞉2, 7꞉3, 6꞉4, 5꞉5, or 4꞉6, respectively). Gastric ulcer models were established by intragastric administration of anhydrous ethanol after 6 days of preventive infusion. The mice were killed 6 days after the treatments. The whole stomach was opened to observe gross morphology of gastric mucosa. The pathological changes of gastric tissue were observed under microscope, and serum samples were collected to detect the contents of superoxide dimutase (SOD), malondialdehyde (MDA), NO, and endothelin-1 (ET-1). The Rhizoma Coptidis and Atractylodes decoction significantly decreased ulcer area (P<0.001), and the effects of compound formula are better than those of Coptidis and Atractylodes alone (P<0.05, P<0.01, or P<0.001). The anti-ulcer effect of compound formula (Coptidis꞉Atractylodes=6꞉4) was the best one, and the anti-gastric ulcer effect of the high-dose group was significantly better than that of the ranitidine-positive group (P<0.001). The ranitidine positive drug group, the high-dose group of Rhizoma Coptidis, the high-dose group of Atractylodes, and the high-dose group of Rhizoma Coptidis-Atractylodes (6꞉4) significantly reduced MDA, ET-1 (P<0.01 or P<0.001), and significantly increased SOD, NO in serum (P<0.01 or P<0.001). Rhizoma Coptidis and Atractylodes decoction exerts the effect on preventing ethanol-induced gastric ulcer in mice in a ratio-dependent and dose-dependent manner. The mechanism might be related to anti-oxidation and relaxion of blood vessels. The combination of the two drugs shows a synergistic effect.

Chrysin Modulates Genes Related to Inflammation, Tissue Remodeling, and Cell Proliferation in the Gastric Ulcer Healing.

Chrysin exhibits anti-inflammatory and antioxidant activities. Here, the gastroprotective effect of chrysin was investigated in mouse models of gastric ulcer induced by absolute ethanol, acetic acid, and ischemia-reperfusion injury. The gastric-healing effect was evaluated at 7 and 14 days after treatment; the mechanism of action was verified using the expression of metalloproteinase 2 (MMP-2) and 9 (MMP-9), caspase-3, cyclooxygenase 1 (COX-1) and 2 (COX-2), epidermal growth factor (EGF), and interleukin-10. Chrysin (10 mg/kg) inhibited macroscopic lesions and increased catalase activity in the mouse model established using absolute ethanol. It ameliorated the gastric ulcer caused by acetic acid by improving the expression of inflammatory genes such as COX-2, inhibiting negative remodeling promoted by MMP-9, increasing cell proliferation effect via EGF, and reducing cellular apoptosis by modulating caspase-3. A faster healing effect was evident in the first 7 days of treatment compared to 14 days of treatment, indicating the pharmacological potential of chrysin. Overall, these results demonstrate the potent effect of chrysin in the gastrointestinal tract and elucidate the genes involved in the healing of gastric ulcers. Moreover, an increase in the levels of gastric mucosa defensive factors is involved in the activity of chrysin in the gastric mucosa.