Acetic Acid-induced Ulcer Model Research Articles

(-)-Fenchone Prevents Cysteamine-Induced Duodenal Ulcers and Accelerates Healing Promoting Re-Epithelialization of Gastric Ulcers in Rats via Antioxidant and Immunomodulatory Mechanisms.

(-)-Fenchone is a naturally occurring monoterpene found in the essential oils of Foeniculum vulgare Mill., Thuja occidentalis L., and Peumus boldus Molina. Pharmacological studies have reported its antinociceptive, antimicrobial, anti-inflammatory, antidiarrheal, and antioxidant activities. The preventive antiulcer effects of (-)-Fenchone were assessed through oral pretreatment in cysteamine-induced duodenal lesion models. Gastric healing, the underlying mechanisms, and toxicity after repeated doses were evaluated using the acetic acid-induced gastric ulcer rat model with oral treatment administered for 14 days. In the cysteamine-induced duodenal ulcer model, fenchone (37.5-300 mg/kg) significantly decreased the ulcer area and prevented lesion formation. In the acetic acid-induced ulcer model, fenchone (150 mg/kg) reduced (p < 0.001) ulcerative injury. These effects were associated with increased levels of reduced glutathione (GSH), superoxide dismutase (SOD), interleukin (IL)-10, and transforming growth factor-beta (TGF-β). Furthermore, treatment with (-)-Fenchone (150 mg/kg) significantly reduced (p < 0.001) malondialdehyde (MDA), myeloperoxidase (MPO), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and nuclear transcription factor kappa B (NF-κB). A 14-day oral toxicity investigation revealed no alterations in heart, liver, spleen, or kidney weight, nor in the biochemical and hematological parameters assessed. (-)-Fenchone protected animals from body weight loss while maintaining feed and water intake. (-)-Fenchone exhibits low toxicity, prevents duodenal ulcers, and enhances gastric healing activities. Antioxidant and immunomodulatory properties appear to be involved in its therapeutic effects.

Abstract 1193: Sensory innervation directly promotes gastric cancer and modulates the tumor microenvironment

Abstract Tumor innervation contributes directly to cancer progression, but there appears to be organ-specific variation in the type of innervation. While our previous studies showed cholinergic signaling promoted gastric cancer and vagal denervation inhibited gastric cancer, it is noteworthy that sensory nerves comprise 80% of the vagal axons. To investigate the role of sensory innervation in gastric carcinogenesis, we performed retrograde neural tracing and identified CGRP+ peptidergic neurons in nodose ganglia and dorsal root ganglia as primary gastric sensory neurons. While VAChT+ parasympathetic nerves are the main nerves innervating the normal stomach, CGRP+ sensory nerves show the greatest degree of expansion in mouse gastric tumors. Indeed, mouse gastric tumors show upregulation of NGF, a growth factor essential for sensory nerve survival, and gastric NGF overexpression in an NGF knock-in mouse also resulted in increased sensory innervation. Inhibition of NGF/Trk signaling by Entrectinib markedly attenuates NGF-dependent sensory nerve expansion. In addition to overall increased axonogenesis of sensory nerves, mouse models of gastric cancer showed upregulation of αCGRP peptide in gastric tumors and Calca mRNA in gastric sensory neurons, indicating increased activation of sensory neurons during gastric carcinogenesis. To study the effect of such activation, sensory neurons were then directly activated by treatment of Trpv1-Cre;hM3Dq mice with clozapine-N-oxide (CNO), which led to marked gastric hyperplasia with increased proliferation. Interestingly, in an acetic acid-induced ulcer model, activation of sensory neurons reduced the ulcer size and strongly promoted gland regeneration. Activation of sensory neurons, in a syngeneic, orthotopic model of gastric cancer in the Trpv1-Cre;hM3Dq mice, led to a significant increase in tumor volume, Ki-67+ cancer cells, CD31+ vessels and M2 macrophage polarization, as well as decreased CD8+ T cells. Analysis of available single-cell transcriptome data from mouse and human stomach showed that Calcrl/Ramp1 (CGRP receptors) are expressed in gastric epithelial cells and most stromal cells, while the expression levels of Tacr1 (receptor for Substance P) and Sstr1-5 (receptors for Somatostatin) were much lower. Importantly, some Calcrl/Ramp1+ cells are proliferative cells with strong Ki-67 expression. Our data show that Calcrl is also overexpressed in mouse gastric tumors, while TCGA data reveals significant upregulation of CALCRL in human gastric cancers and that high expression of CALCRL is correlated with poor overall survival. Finally, we established a co-culture model using DRGs and gastric cancer organoids, and found that sensory nerves can generate synaptic-like terminals on cancer organoids. In conclusion, our data indicate that sensory innervation directly promotes gastric cancer growth and also modulates the tumor microenvironment. Citation Format: Xiaofei Zhi, Feijing Wu, Jin Qian, Yosuke Ochiai, Guodong Lian, Ermanno Malagola, Timothy C. Wang. Sensory innervation directly promotes gastric cancer and modulates the tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1193.

Brazilian Red Propolis Accelerates Gastric Healing and Reduces Gastric Submucosal Layer Inflammation in Ultrasound-Monitored Rats.

Propolis has been used for the treatment of gastric disturbances in folk medicine, nevertheless, the gastric healing effects of Brazilian red propolis have not been unveiled. This study aimed to assess the gastric healing effect of the hydroalcoholic extract of red propolis (HERP) in the acetic acid-induced ulcer model. Rats under acetic acid-induced-ulcer were treated with HERP (100 mg/kg, p.o.) twice a day for seven days. Histological changes, oxidative stress, and inflammatory parameters were analyzed in the gastric tissue. Moreover, the gastric wall thickness was measured by ultrasound. The in vitro cytotoxicity of HERP and cellular migration of fibroblasts were evaluated. The treatment with HERP promoted gastric healing, reducing gastric wall thickness, macroscopic lesion area, and histopathological damages compared to the vehicle. Moreover, HERP reduced oxidative stress and inflammation in the gastric tissue but did not change mucin or collagen levels. HERP did not show signs of toxicity either in vivo or in vitro. HERP displayed a healing effect in vivo by reducing oxidative stress and inflammation. These data contribute to validating the popular use of this product in the treatment of gastric disorders and advance scientific knowledge in the search for new drugs for the management of gastric ulcers.

Evaluation of the Antiulcer Activity of Methanolic Extract and Solvent Fractions of the Leaves of Calpurnia aurea (Ait.) Benth. (Fabaceae) in Rats.

Introduction In Ethiopia, traditionally, the leaves of Calpurnia aurea have been utilized to treat peptic ulcer disease. Therefore, the objective of the present study was to examine the antiulcer activity of Calpurnia aurea hydromethanolic leaf extract and solvent fractions in rats. Methods The ulcer-healing potential of the crude test extract was assessed in rats by adopting pyloric ligation-, acidified ethanol-, and acetic acid-induced ulcer methods; while, in solvent fractions, the acidified ethanol-induced ulcer model was used. In all models, three serial test doses (100, 200, and 400 mg/kg) were given and the antiulcer activity was investigated. Standard drugs like sucralfate (100 mg/kg), omeprazole (20 mg/kg), and cimetidine (100 mg/kg) have been used as a positive control; whereas distilled water (10 mL/kg) was used as the negative control. Parameters like ulcer index, total acidity, pH, gastric volume, and gastric mucin level were all measured. Results In an acute toxicity study, the test extract at the limit test dose (2 g/kg) was safe following a single dose administration. In pyloric ligation-induced ulcers, the plant extract at 200 and 400 mg/kg significantly reduced the ulcer index, the volume of stomach secretion, and total acidity while raising gastric pH and mucus content (P < 0.05). Likewise, in the acidified ethanol- and acetic acid-induced ulcer models, the extract at both test doses (200 and 400 mg/kg) also displayed a substantial reduction (P < 0.05) in ulcer index. Among the fractions, the ethyl acetate fraction revealed remarkable cytoprotective activity at all test doses and the aqueous fraction at 400 mg/kg (P < 0.05). In contrast, the effect of chloroform fraction was found to be negligible. The peak ulcer inhibition was noted at 400 mg/kg of ethyl acetate fraction (52.4%). Conclusion The study showed that the crude extract and solvent fractions possess remarkable antiulcer activity.

Lupeol Stearate Accelerates Healing and Prevents Recurrence of Gastric Ulcer in Rodents.

Objective The focus of this study was to evaluate the gastric healing effect of lupeol stearate (LS) and its ability to minimize ulcer recurrence in rodents. Methods To evaluate the gastric healing properties of LS, rats were subjected to 80% acetic acid-induced ulcer model and treated with vehicle, LS (1 mg/kg, p.o.), or omeprazole (20 mg/kg, p.o.), twice daily by seven days. The gastric ulcers were evaluated macroscopically, histologically, and biochemically. To evaluate the effects of LS in gastric ulcer recurrence, mice were ulcerated with 10% acetic acid and treated with vehicle, LS (1 mg/kg, p.o.), or ranitidine (100 mg/kg, p.o.), twice a day for ten days. Then, ulcer recurrence in these animals was induced by IL-1β at five days after the treatment period. Results The oral treatment with LS accelerated gastric healing by 63% in rats compared to the vehicle group, evidenced by histological improvement and increased gastric mucin levels. Moreover, the gastric healing effects of LS in rats were accompanied by an elevation in glutathione S-transferase activity and a reduction in myeloperoxidase activity. Furthermore, the LS treatment reduced the recurred lesions in mice. Conclusions The oral treatment of LS accelerates gastric healing in rats by favoring mucus production and reducing neutrophil migration, and it also can reduce ulcer recurrence. These data highlighted this compound as promising for developing new pharmacological strategies for the management of gastric ulcer.

Gastroprotective Activity Of Methanol Extract Of Mesocarp Of Unripe Carica Papaya Linn. Fruit On Experimentally-induced Gastric Ulcer In Wistar Rats

Background: Peptic ulcer affects up to 10 % of the world’s population. There has been renewed interest in identifying natural drug sources with gastroprotective activity. Unripe Carica papaya fruit is used traditionally for the treatment of various gastrointestinal disorders including peptic ulcer which may have not been well explored. Objective: The aim of this study was to determine the gastroprotective activity of methanol extract of mesocarp of unripe Carica papaya fruit (MECP) on experimentally-induced gastric ulcer in Wistar rats. Methodology: Forty-six (46) wistar rats (150 g to 170 g) were used for the studies. Six (6) were used for acute toxicity testing using OECD method no.423. Graded doses of MECP (500, 1000 and 1500 mg/kg) were administered as gastroprotective agents, omeprazole and cimetidine were standard drugs used for ethanol-induced and acetic acid-induced ulcer models respectively. Thereafter, 20 rats each were used for ethanol-induced and acetic acid-induced ulcer models to induce gastric ulcers. All drugs and extracts administration were via oral route. Subsequently, animals were euthanized; stomachs excised, cut open and measured to examine the extent of ulceration and level of protection by the MECP. Results: Phytochemical screening showed MECP contains alkaloids, flavonoids, saponins, glycosides, tannins and terpenoids. Anthraquinones were absent. Results of acute toxicity test indicated that MECP is relatively safe with LD50 &gt; 5000 mg/kg. In ethanol-induced ulcer model, rats administered with 1000 mg/kg MECP had the least mean ulcer index (0.917 cm2 ± 0.086) with the highest ulcer protection percentage (76.95 %) of all the extract doses, relative to the standard (omeprazole) with 77.93 % protection. Reduction in mean ulcer index was recorded across the MECP groups for analysis of variance, using Dunnetts post-hoc test for multiple comparison, but showed no statistically significant difference between them. For acetic acid-induced ulcer model, MECP at the lowest dose (500 mg/kg) elicited the least mean ulcer index (0.678 cm2± 0.102) with 87.54 % ulcer protection in a similar manner to cimetidine (20 mg/kg) which had 0.600 cm2 + 0.144 mean ulcer index with 88.97 % ulcer protection. All doses of MECP showed reduction in mean ulcer index when compared to (5.442 cm2 ± 0.511) of the untreated group (normal saline) with no statistically significant difference recorded. Conclusion: MECP has gastroprotective and ulcer healing effects on ethanol-induced ulcer and acetic acid-induced ulcer in Wistar rats. This confirms scientifically, the traditional use of mesocarp of unripe Carica papaya fruit in treatment of peptic ulcer

Hydromethanolic Crude Extract of the Leaf of Urtica simensis Hochst. ex. A. Rich. (Urticaceae) Acquires Appreciable Antiulcer Effect: Validation for In Vivo Antiulcer Activity.

Background Urtica simensis has been used for the treatment of peptic ulcer disease in Ethiopian folkloric medicine by drinking its juice after boiling the semicrushed leaf. To our latest understanding, no in vivo study was available regarding its antiulcer activity. The present study was done to appraise the ulcer-protective and ulcer healing activity of hydromethanolic crude extract of leaf of U. simensis in rats. Methods Preliminary qualitative phytochemical screening and oral acute toxicity were carried out using a standard protocol. To validate U. simensis in vivo antiulcer potential pyloric ligature, cold restraint stress and acetic acid-induced ulcer models were employed. The extracts (100, 200, and 400 mg per kg of body weight per day), standard treatment (omeprazole 20 mg/kg/day), and vehicle (distilled water 10 ml/kg/day) were given to treatment, positive, and negative controls by oral gavage, respectively. Parameters were then evaluated accordingly after the humane scarification of rats. Results Any sign of toxicity was not observed in the oral acute toxicity test. The crude extracts exerted a significant (P < 0.05) inhibition of ulcer risk compared to the negative control. In the pylorus ligation-induced ulcer model, its antisecretory activity was in a dose-dependent manner. The highest gastroprotective effect (67.68%) was exhibited by the 400 mg/kg/day dose of 80% methanolic crude extract. Regarding the chronic ulcer model, treatment at a dosage of 100, 200, and 400 mg/kg/day cures ulcers by 33.54%, 58.33%, and 67.07%, respectively, as compared to the negative control groups remarkably. Conclusion The findings of the present study confirmed the safety and a promising in vivo ulcer healing and antiulcerogenic activity of U. simensis, thus supporting the traditional claim. In-depth investigations on the plant, however, are highly recommended.

Effect of p-cymene and rosmarinic acid on gastric ulcer healing – Involvement of multiple endogenous curative mechanisms

Backgroundp-Cymene and rosmarinic acid are secondary metabolites found in several medicinal plants and spices. Previous studies have demonstrated their anti-inflammatory, antioxidant, and cytoprotective effects. PurposeTo evaluate their gastroduodenal antiulcer activity, gastric healing and toxicity in experimental models. MethodsPreventive antiulcer effects were assessed using oral pre-treatment on HCl/ethanol-induced gastric lesions and cysteamine-induced duodenal lesions models. Gastric healing, the underlining mechanisms and toxicity after repeated doses were carried out using the acetic acid-induced gastric ulcer rat model and oral treatment for 14 days. ResultsIn the HCl/ethanol-induced gastric ulcer and cysteamine-induced duodenal injury, p-cymene and rosmarinic acid (50–200 mg/kg) decreased significantly the ulcer area, and so prevented lesions formation. In the acetic acid-induced ulcer model, both compounds (200 mg/kg) markedly reduced the ulcerative injury. These effects were related to an increase in the levels of reduced glutathione (GSH) and interleukin (IL)-10, and due to a decrease in malondialdehyde (MDA), IL-1β, tumor necrosis factor (TNF)-α, total and mitochondrial reactive oxygen species (ROS) levels. Downregulation of factor nuclear kappa B (NFκB) and enhanced expression of suppressor of cytokine signaling (SOCS)3 were also demonstrated. Furthermore, positive vascular endothelial growth factor (VEGF), metalloproteinase (MMP)-2, and cyclooxygenase (COX-2)-stained cells were increased in treated groups. Treatment also upregulated the platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), transforming growth factor (TGF)-β and epidermal growth factor receptor (EGFR) in gastric tissues. In isolated gastric epithelial cells this healing effect seems to be linked to a modulation of apoptosis, proliferation, survival and protein phosphorylation, such as the extracellular signal-regulated kinases (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK). Oral toxicity investigation for 14 days revealed no alterations in heart, liver, spleen, and kidneys weight nor the biochemical and hematological assessed parameters. p-Cymene and rosmarinic acid also protected animals from body weight loss maintaining feed and water intake. ConclusionsData altogether suggest low toxicity, antiulcer and gastric healing activities of p-cymene and rosmarinic acid. Antioxidant and immunomodulatory properties seem to be involved in the curative effect as well as the induction of different factors linked to tissue repair.

Dual role of eugenol on chronic gastric ulcer in rats: Low-dose healing efficacy and the worsening gastric lesion in high doses

This study evaluated the gastric healing activity of eugenol, the main bioactive compound from clove (Syzygium aromaticum) essential oil. Five groups of female Wistar rats were submitted to acetic acid-induced ulcer model and treated with Vehicle (1 ml/kg, p.o.), eugenol (1, 10 or 100 mg/kg, p.o) or omeprazole (20 mg/kg, p.o), twice a day, by seven or fourteen days. Macroscopic, microscopic, and biochemical analyses were performed in the ulcerated site. Eugenol (1 mg/kg, p.o) administered by 7 or 14 days accelerated the gastric healing process by 33% and 52%, respectively. The healing action of eugenol was accompanied by the rescue on the histological architecture and the normalization of the superoxide dismutase and catalase activity. Moreover, eugenol (1 mg/kg, p.o) reduced the gastric mucosal myeloperoxidase activity and increased the mucin secretion. In contrast, eugenol at a dose of 100 mg/kg administered by 7 days enhanced 49% the ulcerated area, but at 10 mg/kg did not change the ulcer area after 7 or 14 days of treatment. Thus, although the gastric healing potential of eugenol is evident, its administration needs to be manageable in an adequate dose due to the worsening of the gastric lesion with its use in high doses.

Sphaeranthus senegalensis DC: Evaluation of chemical constituents, oral safety, gastroprotective activity, and mechanism of action of its hydroethanolic extract

Ethnopharmacological relevanceSphaeranthus senegalensis DC is a seasonal herb with a spicy smell that grows wild in wet grounds of tropical Africa and Asia. The plant is used in folk medicine for the treatment of various diseases; that includes its use to treat gastric ulcers. Aim of the studyThis study aimed to investigate the chemical constituents of the hydroethanolic extract of Sphaeranthus senegalensis DC and evaluate its oral safety, gastroprotective activity, and mechanisms of action using laboratory models in rats and mice. Materials and methodsHydroethanolic extract (70%) of the powdered whole dried material was prepared, and chemical constituents of the resultant extract (denoted HESs) standardized using the high-performance liquid chromatography (HPLC) method. The safety profile of HESs was assessed using 2000 mg/kg, oral (p.o.) for Hippocratic screening in mice, and 800 mg/kg, p.o. for 28 days subchronic toxicity assay in rats. The gastroprotective effect of HESs (25, 100, and 400 mg/kg, p.o.) was investigated using acidified ethanol, piroxicam, water immobilization stress, and acetic acid-induced ulcer models. The gastroprotective mechanisms of HESs were evaluated using its effect on gastric mucus protection, nitric oxide modulation, gastric juice secretory parameters, catalase and myeloperoxidase activities. Histological analysis of the stomach tissues was also carried out. ResultsThe HPLC analysis indicated the presence of 25.94% phenolics (gallic acid, caffeic acid, and ferulic acid) and 14.53% flavonoids (rutin, morin, luteolin, quercetin, and apigenin). Hippocratic screening and the 28 days subchronic study indicated that HESs is generally safe. Result shows that oral administration of HESs (25, 100 and 400 mg/kg) alleviated the severity of the gastric ulcers induced by acidified ethanol by 35.65% (p < 0.05), 48.70% (p < 0.05) and 78.02% (p < 0.001) respectively; exhibited gastroprotective effect against the gastric lesions induced by piroxicam by 37.97% (p < 0.05), 53.27% (p < 0.05) and 76.23% (p < 0.001) respectively; and decreased the severity of the water immobilization stress-induced gastric ulcers by 32.43% (p < 0.05), 55.26% (p < 0.01) and 74.05% (p < 0.001) respectively, when compared to the vehicle control group. The mechanisms of action assays indicated that the gastroprotective activity was mediated mainly through gastroprotection, antisecretory, and antioxidant activities. Histological analysis showed it inhibited epithelial cell loss, vascular damage, and leucocyte infiltration. ConclusionHESs contains useful phytochemicals, is safe, and exhibited significant gastroprotective action. The results provided justification for its claim in the treatment of gastric ulcers and its evaluation for potential application as a gastroprotective agent.

Role of Daucus carota in Enhancing Antiulcer Profile of Pantoprazole in Experimental Animals.

The carrot plant (Daucus carota) and its components are traditionally reported for the management of gastric ulcers. This study was performed to evaluate the role of carrot when administered concurrently with a conventional antiulcer treatment, pantoprazole, in alleviating gastric and duodenal ulcers in female experimental animals. The study involved standard animal models to determine the ulcer preventive effect using pylorus ligation, ethanol, and stress induced acute gastric ulcer models and duodenal ulcer models involving cysteamine. Acetic acid-induced chronic gastric ulcer and indomethacin-induced gastric ulcer models were used to evaluate the ulcer healing effect. Carrot fruit (500 mg/kg) and its co-administration with pantoprazole produced significant protection in an ethanol- and stress-induced acute gastric ulcer and cysteamine-induced duodenal ulcer. The healing of the acetic acid-induced chronic gastric ulcer was also augmented with this combination. Both total proteins and mucin contents were significantly increased in indomethacin-induced gastric ulcers. Similarly, in pylorus ligation, the pepsin content of gastric juice, total acidity, and free acidity were reduced. Overall, both ulcer preventive effects and ulcer healing properties of the pantoprazole were significantly enhanced in animals who received the co-administration of carrot fruit (500 mg/kg).

Antidiabetic and antiulcerative potential of Garcinia lanceifolia Roxb. bark

BackgroundGarcinia lanceifolia Roxb. has been used by many ethnic communities of Northeast India to mitigate various disorders like dyspepsia, ulcers, diabetes, etc. However, a robust scientific study on its antidiabetic and antiulcer potential is unavailable till date. The aim of this present study is to scientifically validate if the antidiabetic and antiulcer effects reported by the ethnic tribes of Assam has any scientific value or not. The effects were tested in adult Wistar albino rats using approved animal models for preclinical testing of pharmacological activities.ResultsThe hydroalcoholic extract of the bark of Garcinia lanceifolia Roxb. was prepared and its LD50 was calculated. The LD50 was determined to be greater than 5000 mg/kg body weight. The extract at doses of 250 mg/kg body weight and 500 mg/kg body weight was found to exhibit a very potent dose-dependent antidiabetic activity. The results were backed by a battery of test including analysis of serum levels of blood glucose, lipid profiles, in vivo antioxidant enzymes, and histopathological studies. Evidence of dose-dependent antiulcer activity of the extract was backed by robust scientific data. It was found that HAEGL induced a significant dose-dependent increase in the ulcer index in both alcohol-induced and acetic acid-induced ulcer models, which was evident from the macroscopic observation of the inner lining of the gastric mucosa and the histological evaluation of the extracted stomach.ConclusionThe results suggested that the bark of Garcinia lanceifolia (Roxb.) has significant antidiabetic and antiulcer potential. Further studies with respect to the development herbal dosage forms and its safety evaluation are required.

Evaluation of the Anti-Ulcer Activity of Hydromethanolic Crude Extract and Solvent Fractions of the Root of Rumex nepalensis in Rats.

BackgroundRumex nepalensis(RN) Spreng has been used to treat ulcer disease in Ethiopian folk medicine. This study aimed to determine the anti-ulcer activity of hydroalcoholic root crude extract and solvent fractions of R. nepalensis in rats.MethodsThe effect of R. nepalensis crude hydromethanolic extract and solvent fractions at doses (100, 200, 400 mg/kg/day) and repeated dosing (200 mg/kg/day for 10 and 20 days) was examined on ulcers in rats in pyloric ligation-, cold restraint stress-, and acetic acid-induced ulcer models. Cimetidine (100 mg/kg/day) and/or Omeprazole (20 mg/kg/day) were used as standard drugs and served as a positive control. Data were analyzed by one-way ANOVA post hoc followed by a Tukey HSD test with SPSS software version 24.0, and P≤ 0.05 was considered as statistically significant.ResultsIn the pylorus ligation-induced ulcer model, pretreatment with the crude extract significantly reduced the degree of gastric secretions, pH, total acidity, and ulcerations in a dose-dependent manner. Gastroprotection offered by the R. nepalensis 400 mg/kg test extract was comparable to that of the standard. Among fractions, the ethyl acetate fraction at 400 mg/kg had the highest protection of ulcer but the chloroform fraction was ineffective. In the cold restraint stress-induced ulcer model, R. nepalensis at 200 and 400 mg/kg reduced the lesion index significantly (P<0.01). With relevant chronic ulcer model treatment, a dose of R. nepalensis at 200 and 400 mg/kg healed ulcers significantly with a curative ratio of 53.22% and 54.59%, respectively.ConclusionFrom this study, it is concluded that hydromethanolic crude extract and solvent fractions of R. nepalensis root showed promising anti-ulcer activity. This upholds its folkloric use. Thus, it is considered as a possible source to develop a new anti-ulcer agent.

Gastric healing effect of p-coumaric acid isolated from Baccharis dracunculifolia DC on animal model.

The p-coumaric acid is a phenolic compound present in large quantities in the extract of Baccharis dracunculifolia DC, a Brazilian medicinal plant used to treat gastric ulcer. Given the necessity for finding new chemical components capable of accelerating gastric healing, in this study, the effects of the p-coumaric acid were evaluated in the acetic acid-induced ulcer model in rats, where histological, inflammatory, and oxidative parameters were analyzed. The healing property was also evaluated in the scratch assay on fibroblast cells (L929) and the cytotoxicity of p-coumaric acid was assessed in both L929 and human gastric adenocarcinoma (AGS) cells by MTT assay. The treatment with p-coumaric acid (10mg/kg, p.o.) for 7days, twice a day, decreased by 44.6% the acetic acid-induced gastric ulcer compared with the vehicle-treated group. The vehicle control-treated group showed a larger extension of the ulcer base and an extensive damage into the mucosa and submucosa layers, which were mitigated by the treatment with p-coumaric acid. This beneficial effect was also associated with increased levels of mucin and reduced glutathione, decreased amount of lipid hydroperoxides, and increased superoxide dismutase and catalase activities without interfering with the activity of myeloperoxidase in the gastric tissue. The compound promoted the restructuring of the cell monolayer in the scratch test and did not show toxicity in the L929 cell line, while reduced the viability of the AGS, a lineage of human gastric adenocarcinoma. Thus, p-coumaric acid may be considered a natural source for the treatment of gastric ulcers, by reinforcing protective factors of gastric mucosa and by accelerating gastric healing.

Gastroprotective and Healing Effects of Polygonum cuspidatum Root on Experimentally Induced Gastric Ulcers in Rats.

Polygonum cuspidatum is widely used as food and medicine in Korea, China, and Japan. Its major bioactive components, resveratrol and emodin, reportedly protect against gastric lesions. We therefore aimed to investigate: (1) the gastroprotective effects of P. cuspidatum roots in hydrochloric acid/ethanol (HCl/EtOH)- and indomethacin-induced acute gastric ulcer rat models; (2) the healing effects in an acetic acid-induced ulcer model; and (3) potential mechanisms by measuring gastric acid secretion-related parameters in a pyloric ligation-induced ulcer model, and by measuring antioxidant enzyme and prostaglandin E2 levels in the gastric tissue of HCl/EtOH-treated rats. Oral administration of P. cuspidatum extract (PCE) at doses of 100 and 300 mg/kg significantly decreased HCl/EtOH- and indomethacin-induced gastric lesions. PCE at 300 mg/kg significantly reduced gastric lesions in acetic acid-induced ulcers. PCE increased superoxide dismutase (SOD) activity and glutathione (GSH) and prostaglandin E2 levels in gastric tissue, whereas it did not alter gastric acid secretion-related parameters. Our findings indicate that PCE has gastroprotective effects against HCl/EtOH and non-steroidal anti-inflammatory drugs (NSAIDs) and promotes healing of acetic acid-induced ulcers. These gastric mucosal protection and ulcer healing effects are associated with antioxidant effects and the augmentation of prostaglandin E2 and suggest that P. cuspidatum might be a promising preventive and therapeutic agent for treating gastric ulcers.

Preliminary screening of anti-ulcerati ve colitis activity of aqueous leaf extract of Spondias mombin Linn. (Anacardiaceae) and the possible mechanisms of action in rats

Spondias mombin L. (Anacardiaceae) commonly known as ‘yellow mombin’ is a multipurpose herb cultivated in parts of the Brazilian Northeast for its edible fruits, oil and leaves. The bark is used to carve figures and leaves and roots used as medicine. Efforts in this study were devoted to evaluating the effect of aqueous leaf extract of Spondias mombin Linn. on SMB sub-acute dosing in a rat model of acetic acidinduced ulcerative colitis and acetic-acid induced ulcerative colitis (curative) models. Three graded doses of the extract were administered orally (50, 100 and 200mg/kg) for the prophylactic model and 200mg/kg for the curative model. The involvement of endogenous nitric oxide, prostaglandins and potassium ion in the cytoprotective action of S. mombin L. was also investigated. The extract showed a significant (p&lt;0.05) colonic cytoprotective effect in acetic-acid induced ulcerative colitis (prophylactic) and acetic-acid induced ulcerative colitis (curative) models when compared to control. Antioxidant analysis showed the ability of S. mombin L. to attenuate oxidative stress by decreasing the lipid peroxide level and to inhibit accumulation of free radicals’ generation during LPO (lipid peroxidation) process. S. mombin L. showed presence of flavonoids, tannins, reducing sugar, cardiac glycosides and steroids/terpenes. S. mombin L. exhibited cytoprotective effects in all acetic-acid induced ulcer models via the mechanism of reducing the aggressive activity of the immune system on the colonic mucosa thereby protecting the colonic mucosa.

Evaluation of anti-ulcer activity of extract of Moringa oleifera Lam. using Acetic acid induced ulcer model

Moringa oleifera Lam commonly known as Moringa, a native plant from Africa and Asia, and the most widely cultivated species in Northwestern India, is the sole genus in the family Moringaceae. It comprises 13 species from tropical and subtropical climates, ranging in size from tiny herbs to massive trees. It is grown for its nutritious pods, edible leaves and flowers and can be utilized as food, medicine, cosmetic oil or forage for livestock. Its height ranges from 5 to 10 m. Several studies have demonstrated the beneficial effects in humans. MO has been recognized as containing a great number of bioactive compounds. The most used parts of the plant are the leaves, which are rich in vitamins, carotenoids, polyphenols, phenolic acids, flavonoids, alkaloids, glucosinolates, isothiocyanates, tannins and saponins. The present investigation was carried out to evaluate anti-ulcer activity of various extract of the plant. Keywords: Moringa oleifera, Anti-ulcer activity, acetic acid induced

Evaluation of the antiulcer activity of the aqueous stem bark extract of Balanites aegyptiaca L Delile in Wistar rats

Ethnopharmacological relevanceBalanites aegyptiaca L. Delile (Zygophyllaceae) is a perennial tree that is mostly found in Africa, south Asia and most desert environments. Decoctions of its stem barks are used in northern Nigeria for the treatment of ulcers and stomach issues. Other folkloric uses include treatment of wounds, malaria, dysentery, asthma, and fever.Aim of the study: The present study evaluated the antiulcer activity of the aqueous stem bark extract of Balanites aegyptiaca in Wistar rats. Materials and methodsThe antiulcer activity of the aqueous stem bark extract of Balanites aegyptiaca (125, 250 and 500 mg/kg, p.o.) was evaluated in ethanol, indomethacin, pylorus ligation and acetic acid-induced ulcer models in rats. Parameters such as mean ulcer indices and percentage ulcer inhibition were assessed in ethanol, indomethacin and acetic acid-induced ulcer models while gastric volume, pH, and titratable acidity were evaluated in the pylorus ligation ulcer model. ResultsThe extract at the doses of 125, 250 and 500 mg/kg caused a significant (p < 0.01), dose dependent reduction in mean ulcer indices in the ethanol and indomethacin ulcer models. A significant dose dependent reduction in mean ulcer indices were also observed after three (p < 0.01) and seven (p < 0.001) days of treatment with the extract in acetic acid-induced ulcer model. In pylorus ligation model, the gastric secretion parameters (gastric volume, pH, and titratable acidity) showed no alteration in the different doses of the extract when compared to the control. ConclusionOur study showed that the aqueous stem bark extract of Balanites aegyptiaca possesses gastroprotective and ulcer healing properties and therefore not only provides scientific evidence for its folkloric use in the treatment of ulcers but also showed evidence that it may be used in the development of a new phytotherapeutic formulation for the treatment of peptic ulcer.

Hydroalcoholic extract from Baccharis dracunculifolia recovers the gastric ulcerated tissue, and p-coumaric acid is a pivotal bioactive compound to this action.

Baccharis dracunculifolia is a medicinal plant native to southeastern Brazil and is the main botanical source used by bees (Apis mellifera) in the manufacture of green propolis and display similar gastroprotective action and chemical profile. This article reports the healing gastric ulcer activity of the hydroethanolic extract of B. dracunculifolia (HEBD) in an acetic acid-induced ulcer model. In addition to the extract, the isolated compounds ferulic acid, p-coumaric acid, caffeic acid, baccharin, and aromadendrin-4'-O-methyl ether were also assayed. HEBD at a dose of 300 mg/kg reduced the ulcerated area by 49.4% after treatment for 7 days, twice a day. Histological analyses revealed that the margins and base of the ulcer obtained significant regeneration, and periodic acid Schiff base staining showed a 78.2% increase in the mucin levels. The action on the enzymatic antioxidant system demonstrated an increased activity of superoxide dismutase and glutathione-S-transferase, in addition to raising glutathione reduced levels and myeloperoxidase activity. HEBD did not show cytotoxicity in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylterazole bromine test. In vitro, HEBD inhibited the H+ /K+ -ATPase enzyme and showed antioxidant activity in the 2,2 diphenyl-1-picryllydrazyl test. Regarding the isolated compounds, oral administration of p-coumaric acid (15 mg/kg) reduced the ulcerated area by 66.2%. The results suggest that HEBD recovers the gastric ulcerated tissue, raising mucus and antioxidant enzyme levels, and reducing the H+ /K+ -ATPase activity. In addition, the findings confirm that p-coumaric acid is a pivotal bioactive compound on the gastric healing effects elicited by HEBD. © 2019 BioFactors, 45(3):479-489, 2019.

BST-104, a Water Extract of Lonicera japonica, Has a Gastroprotective Effect via Antioxidant and Anti-Inflammatory Activities.

The gastroprotective effects of BST-104 (a water extract of Lonicera japonica) and the mechanisms involved were investigated in murine models of gastritis and peptic ulcer. The gastroprotective effects of BST-104 and its active components were evaluated in rat models of HCl/ethanol-induced gastritis and acetic acid-induced gastric ulcer. After orally administering BST-104, chlorogenic acid, rebamipide (positive control), or vehicle to each animal model, gastric lesion sizes, gastric mucus statuses, proinflammatory cytokine levels, and oxidative stress were measured. Superoxide dismutase (SOD), catalase, and malondialdehyde (MDA) levels and oxidized/reduced glutathione (GSH) ratios in gastric mucosal tissues were measured to evaluate oxidative stress. To clarify the action mechanism of BST-104, we investigated nuclear factor (NF)-κB pathway involvement by real-time polymerase chain reaction (PCR). In the acetic acid-induced ulcer model, oral administration of BST-104 at 50, 100, or 200 mg/kg significantly reduced gastric lesions by 38%, 43%, and 55%, respectively, compared with vehicle controls. BST-104 significantly increased gastric mucus contents and this was accompanied by higher levels of hexosamine, sialic acid, and prostaglandin E2 in gastric mucus. Furthermore, BST-104 treatment increased antioxidant activities, as evidenced by higher levels of catalase, SOD, and oxidized/reduced GSH and lower MDA levels. In addition, BST-104 significantly suppressed proinflammatory cytokine (tumor necrosis factor-α, interleukin [IL]-6, and IL-1β) increases, and real-time PCR showed that BST-104 significantly downregulated NF-κB expression. In summary, BST-104 and its active component, chlorogenic acid, were found to have gastroprotective effects by virtue of their antioxidant and anti-inflammatory properties through downregulation of NF-κB expression.