scholarly journals (-)-Carveol Prevents Gastric Ulcers via Cytoprotective, Antioxidant, Antisecretory and Immunoregulatory Mechanisms in Animal Models

2021 ◽  
Vol 12 ◽  
Author(s):  
Catarina Alves de Lima Serafim ◽  
Maria Elaine Cristina Araruna ◽  
Edvaldo Balbino Alves Júnior ◽  
Leiliane Macena Oliveira Silva ◽  
Alessa Oliveira Silva ◽  
...  
Keyword(s):  
Gastric Ulcer ◽  
Animal Models ◽  
Gastric Secretion ◽  
Gastric Wall ◽  
Lethal Dose ◽  
Mechanisms Of Action ◽  
Gastric Ulcers ◽  
Ethanol Stress ◽  
Gastroprotective Activity ◽  
Pylorus Ligation

Background: (-)-Carveol (p-Mentha-6,8-dien-2-ol) is a monocyclic monoterpenic alcohol, present in essential oils of plant species such as Cymbopogon giganteus, Illicium pachyphyllum and in spices such as Carum carvi (cumin). Pharmacological studies report its antitumor, antimicrobial, neuroprotective, vasorelaxant, antioxidant and anti-inflammatory activity.Hypothesis/Purpose: The objective of this study was to evaluate the acute non-clinical oral toxicity, gastroprotective activity of monoterpene (-)-Carveol in animal models and the related mechanisms of action.Methods: Acute toxicity was assessed according to OECD guide 423 in mice. Ethanol, stress, NSAIDs 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.Results: (-)-Carveol has low toxicity, with a lethal dose 50% (LD50) equal to or greater than 2,500 mg/kg according to OECD guide nº 423. In all gastric ulcer induction methods evaluated, (-)-Carveol (25, 50, 100 and 200 mg/kg, p.o.) significantly reduced the ulcerative lesion in comparison with the respective control groups. To investigate the mechanisms involved in the gastroprotective activity, the antisecretory or neutralizing of gastric secretion, cytoprotective, antioxidant and immunoregulatory effects were evaluated. In the experimental protocol of pylorus ligation-induced gastric ulcer, (-)-Carveol (100 mg/kg) reduced (p < 0.001) the volume of gastric secretion in both routes (oral and intraduodenal). The previous administration of blockers NEM (sulfhydryl groups blocker), L-NAME (nitric oxide synthesis inhibitor), glibenclamide (KATP channel blocker) and indomethacin (cyclo-oxygenase inhibitor), significantly reduced the gastroprotection exercised by (-)-Carveol, suggesting the participation of these pathways in its gastroprotective activity. In addition, treatment with (-)-Carveol (100 mg/kg) increased (p < 0.001) mucus adhered to the gastric wall. Treatment also increased (p < 0.001) levels of reduced glutathione (GSH), superoxide dismutase (SOD) and interleukin-10 (IL-10). It also reduced (p < 0.001) malondialdehyde (MDA), myeloperoxidase (MPO), interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels.Conclusion: Thus, it is possible to infer that (-)-Carveol presents gastroprotective activity related to antisecretory, cytoprotective, antioxidant and immunomodulatory mechanisms.

scholarly journals Hydroxyproline, a Serum Biomarker Candidate for Gastric Ulcer in Rats: A Comparison Study of Metabolic Analysis of Gastric Ulcer Models Induced by Ethanol, Stress, and Aspirin

2014 ◽  
Vol 9 ◽  
pp. BMI.S15918 ◽  
Author(s):  
Kenichiro Takeuchi ◽  
Maki Ohishi ◽  
Keiko Endo ◽  
Kenichi Suzumura ◽  
Hitoshi Naraoka ◽  
...  
Keyword(s):  
Gastric Ulcer ◽  
Gastrointestinal Symptoms ◽  
Drug Effects ◽  
Serum Biomarker ◽  
Gastric Ulcers ◽  
Gastric Injury ◽  
Ethanol Stress ◽  
Metabolomic Profiling ◽  
Inflammatory Drugs ◽  
Common Manifestation

Gastrointestinal symptoms are a common manifestation of adverse drug effects. Non-steroid anti-inflammatory drugs (NSAIDs) are widely prescribed drugs that induce the serious side effect of gastric mucosal ulceration. Biomarkers for these side effects have not been identified and ulcers are now only detectable by endoscopy. We previously identified five metabolites as biomarker candidates for NSAID-induced gastric ulcer using capillary electrophoresis–mass spectrometry (CE–MS)-based metabolomic analysis of serum and stomach from rats. Here, to clarify mechanism of changes and limitations of indications of biomarker candidates, we performed CE–MS-based metabolomic profiling in stomach and serum from rats with gastric ulcers induced by ethanol, stress, and aspirin. The results suggest that a decrease in hydroxyproline reflects the induction of gastric injury and may be useful in identifying gastric ulcer induced by multiple causes. While extrapolation to humans requires further study, hydroxyproline can be a new serum biomarker of gastric injury regardless of cause.

scholarly journals EVALUATION OF ANTI ULCER ACTIVITY OF HYDROALCOHOLIC LEAVES EXTRACT OF LEUCAS ASPERA

2021 ◽  
Vol 9 (2) ◽  
Author(s):  
Surjeet Kumar ◽  
Narendra Patel ◽  
Prabhakar Budholiya
Keyword(s):  
Gastric Ulcer ◽  
Secondary Metabolites ◽  
Lethal Dose ◽  
Folk Medicine ◽  
Gastric Ulcers ◽  
Leucas Aspera ◽  
Pharmacologic Activity ◽  
Pre Treatment ◽  
Repeated Dosing ◽  
Dose Dependent

The main aim of the study was to determine the phytoconstituents present in Leaves of Leucas aspera. The present study was therefore carried out to evaluate the anti-ulcer activity of Hydroalcoholic (70% methanol) leaf extract of Leucas aspera in rats. The effect of Leucas aspera extract on gastric ulcer in rats in indomethacin induced gastric ulcers model and ethanol-induced models was studied using single dosing (100, 200 mg/kg) and repeated dosing (200 mg/kg for 5 days) approaches. Ranitidine (50 mg/kg) and cimetidine (100 mg/kg) were used as the standard drugs. Depending on the model, outcome measures were volume ulcer index. Data were analyzed using one-way analysis of variance and P<0.05 was considered as statistically significant. Leucas aspera significantly (P<0.001) reduced gastric ulcer, respectively, in indomethacin induced gastric ulcers model and ethanol-induced models at the 200 mg/kg dose, which is comparable to the standard drugs. 5 days pre-treatment with Leucas aspera 200 mg/kg exhibited significant (P<0.001) ulcer inhibition. Leucas aspera  possesses both dose-dependent and time-dependent anti-ulcer effect in the two models. The oral median lethal dose (LD50) is estimated to be higher than 2000 mg/kg for the crude hydroalcoholic extract, and secondary metabolites such as flavonoids, tannins, and saponins were present. The findings of this study confirmed that Leucas aspera has anti-ulcer pharmacologic activity due to one or more of the secondary metabolites present in it. Therefore, this study validates its anti-ulcer use in Ethiopian folk medicine. Further investigations on isolation of specific phytochemicals and elucidating mechanisms of action are needed.

scholarly journals Ameliorative effect of Albizzia procera leaves extract against experimentally induced gastric ulcer models in Wistar albino rats

2021 ◽  
Vol 13 (1) ◽  
pp. 308-315
Author(s):  
Vivek Srivastava ◽  
Santosh Kumar Verma ◽  
Neha Mathur ◽  
Kapil Kumar Goel
Keyword(s):  
Gastric Ulcer ◽  
Ethanolic Extract ◽  
Gastric Fluid ◽  
Gastric Ulcers ◽  
Albino Rats ◽  
Traditional Medicines ◽  
Pylorus Ligation ◽  
Ameliorative Effect ◽  
Wistar Albino Rats ◽  
Experimentally Induced

Albizzia procera belongs to family Fabaceae and has several phytoconstituents like flavonoids, terpenes, alkaloids, saponins etc. The plant is commonly used in traditional medicines. The objective of the present study was to assess the ameliorative effect of A. procera leaves extract against an experimentally induced gastric ulcer in albino rats. The antiulcer, antisecretory and cytoprotective properties of an ethanolic extract prepared from the leaves was evaluated. When given in a 200 mg/kg oral (per. os) dose, the extract produced 74% and 85% protection index in ethanol-induced ulcer model and pylorus ligation model, respectively.  Additionally, the extract also prohibited the formation of haemorrhage and edema, significantly lessened catalase activity (p<0.0001) and the lipid peroxidation level (p<0.0001) in the glandular tissue of Wistar albino rats. Furthermore, the extract also significantly diminished the total acidity(p<0.0001) of the gastric fluid by increasing its pH (p<0.0001). The occupancy of different phytoconstituents in the extract, such as flavonoids and tannins were identified that may be responsible for its gastro-protective activity. All these results provide a basis explaining the antiulcer ability of A. procera being useful in the management of gastric ulcers.

scholarly journals Gastric ulcer healing in the rat: kinetics and localisation of de novo procollagen synthesis

Gut ◽  
1997 ◽  
Vol 41 (2) ◽  
pp. 187-194 ◽  
Author(s):  
M Shahin ◽  
A Gillessen ◽  
T Pohle ◽  
C Weber ◽  
D Schuppan ◽  
...  
Keyword(s):  
Gastric Ulcer ◽  
Ulcer Healing ◽  
De Novo ◽  
Gastric Wall ◽  
In Situ Hybridisation ◽  
Muscularis Propria ◽  
Gastric Ulcers ◽  
Type I ◽  
Gastric Ulcer Healing ◽  
Transcript Levels

Background and aims—To gain further insight into the role of the extracellular matrix during healing of peptic ulcers, sequential changes of procollagen expression were studied over 30 days of ulcer healing.Materials and methods—Procollagens α1(I), α1(III), and α1(IV) RNA and their polypeptides were assessed in acetic acid induced rat gastric ulcers by in situ hybridisation and immunohistochemistry.Results—Three days after ulcer induction, intense hybridisation signals were obtained with all probes, with procollagen α1(I) showing the highest transcript levels. Procollagen gene expression remained elevated up to day 15, but was reduced to initial low levels on day 30. Immunohistochemical staining documented increased deposition of the three procollagen types parallel to their respective transcript levels, again with type I showing the earliest and the most prominent deposits. The highest procollagen transcript levels were found in the intact submucosa surrounding the ulcer margins, followed by the muscularis propria and the serosa, with the lamina propria exhibiting the lowest transcript levels.Conclusion—The procollagens studied are regulated differentially at the transcriptional and post-transcriptional levels. The early onset and long duration of procollagen expression as well as the involvement of all layers of the gastric wall points to their central structural and functional role in gastric ulcer healing.

scholarly journals Evaluation of Antiulcerogenic Activity of Clerodendron Infortunatum Extract on Albino Rat Gastric Ulceration

2019 ◽  
Vol 9 (4-A) ◽  
pp. 57-62
Author(s):  
Arun Kumar ◽  
Rahul Shukla ◽  
Anurag Chaudhary
Keyword(s):  
Acetic Acid ◽  
Gastric Ulcer ◽  
Restraint Stress ◽  
Ethanolic Extract ◽  
North India ◽  
Gastric Ulcers ◽  
Albino Rat ◽  
Pylorus Ligation ◽  
Cold Restraint Stress ◽  
Cold Restraint

Clerodendron infortunatum Linn. (Verbenaceae) is an important and widely used medicinal plant, reported to contain active bitter substance like clerodin, has been widely used as tonic and anthelmintic agent in the country sides of North India. Though, variously used in Ayurveda, Unani system of medicine and Homeopathy in case of ailments like diarrhoea, skin disorders, venereal and scrofulous complaints, wounds, post-natal complications, as vermifuge, laxative and cholagogue, for the removal of ascarids in anus, as external applications on tumours, etc., Background: The present study reports the antiulcer properties of 50% ethanolic extract of Clerodendron infortunatum Linn. (Verbenaceae) leaves have assessed in different acute and chronic gastric ulcer models in rats. Methods: EECI (100, 200 and 400 mg/kg body weight) was administered orally, twice daily for 5 days for prevention from ethanol (EtOH), Cold-restraint stress (CRS), Pylorus-ligation (PL) and 10 days for prevention of acetic acid induced ulcers. Results: The EECI showed significant gastric ulcer protective effect in doses of 400 mg/kg, when given twice daily for 5 days against gastric ulcers induced by ethanol (EtOH), cold restraint stress (CRS) and pyloric ligation (PL). EECI showed dose dependent decrease in ulcer index (UI) against ulcers induced by: (i) Ethanol (control UI: 29.52±2.4 mm2/rat, EECI decrease 21.12±2.3 – 5.3±1.0 (ii) Cold restraint stress (CRS) (control UI: 32.13±2.1, EECI decrease 24.02±2.2 – 4.7±1.1 (iii) pylorus ligation (control UI: 29.25±2.4 mm2/rat, EECI decrease 22.32±2.7 – 5.3±1.0, EECI 400 mg/kg significantly healed ulcers induced by 50% acetic acid after 5 (control UI: 32.30 ± 2.9, EECI decrease 26.27±1.9 – 8.56±0.98 and after 10 days treatment (control UI: 29.02 ± 2.6, healing 21.28±2.1 – 5.78±1.2. EECI prevents the oxidative damage of gastric mucosa by blocking lipid peroxidation and by significant decrease in superoxide dismutase, and increase in catalase activity. Conclusions: Our results show that Clerodendron infortunatum Linn. (Verbenaceae)  possess significant gastro-protective activity which might be due to gastric defence factors and clerodin might be the main constituents responsible for this activity.

scholarly journals Anti-Gastric Ulcer Activity of the Water Extract from Payawanorn (Pseuderanthemum Palatiferum)

2018 ◽  
Vol 36 (2) ◽  
pp. 89
Author(s):  
Kannika Inchab ◽  
Parirat Khonsung ◽  
Natthakarn Chiranthanut ◽  
Puongtip Kunanusorn ◽  
Saranyapin Potikanond ◽  
...  
Keyword(s):  
Gastric Ulcer ◽  
Alcian Blue ◽  
Water Immersion ◽  
Gastric Wall ◽  
Water Extract ◽  
Gastric Ulcers ◽  
Control Group ◽  
P Value ◽  
Ulcer Formation ◽  
Traditional Use

Objective: To examine the anti-gastric ulcer activity of Payawanorn (Psuderanthemum palatiferum)  water extract (PPE) in rats.Material and Methods: Evaluation of anti-gastric ulcer activity of PPE was performed using three induced gastric ulcers models: (1) ethanol/hydrochloric acid (EtOH/HCl), (2) restraint water immersion stress and (3) indomethacin. Ulcer indices were determined by microscopic examination (10X). Pylorus ligation and gastric-wall mucus determination were used to investigate the mechanism of anti-gastric ulcer activity of PPE.Results: Oral administration of PPE (150, 300 and 600 mg/kg) significantly inhibited gastric ulcer formation induced by EtOH/HCl, by water immersion restraint stress, and by indomethacin in rats (p-value<0.05). PPE at 600 mg/kg showed a high percent inhibition of gastric ulcer formation in all models. In the pylorus-ligated model, pretreatment with PPE had no effect on pH, acidity output or the gastric acid secretion rate, demonstrating that PPE lacks an anti-secretory effect. Gastric wall mucus was markedly preserved by pretreatment PPE at 600 mg/kg (18.91±2.57 μg alcian blue/g wet stomach) after ethanol-induced ulcer when compared to that the control group (12.38±1.02 μg alcian blue/ g wet stomach).Conclusion: PPE possesses an anti-gastric ulcer effect related to the preservation of gastric mucus, supporting the traditional use of P. palatiferum to treat gastric ulcers.

Topical transplantation of mesenchymal stem cells accelerates gastric ulcer healing in rats

2008 ◽  
Vol 294 (3) ◽  
pp. G778-G786 ◽  
Author(s):  
Yujiro Hayashi ◽  
Shingo Tsuji ◽  
Masahiko Tsujii ◽  
Tsutomu Nishida ◽  
Shuji Ishii ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Gastric Ulcer ◽  
Growth Factor ◽  
Ulcer Healing ◽  
Gastric Wall ◽  
Female Rats ◽  
Male Rats ◽  
Gastric Ulcers ◽  
Gastric Ulcer Healing

Mesenchymal stem cells (MSCs), a subpopulation of adult somatic stem cells, are an attractive stem cell source in regenerative medicine because of their multipotentiality. We examined the effects of MSC transplantation on gastric ulcer healing. Putative MSCs, isolated from bone marrow aspirates of male rats by dish adherence and expanded in culture, were characterized by flow cytometry and reverse transcription-polymerase chain reaction. Gastric ulcers were induced by serosal application of acetic acid on the anterior wall of the stomach in female rats. Either MSCs (labeled with PKH67; 1×107 cells) or vehicle was injected into the gastric wall surrounding the ulcer. The healing process of the ulcer and the influence of anti-vascular endothelial growth factor (VEGF) antibody were examined. CD29-positive, CD90-positive, CD34-negative, and CD45-negative MSCs expressed mRNAs for VEGF and hepatocyte growth factor (HGF). The MSCs were transplantable to the gastric tissue surrounding the ulcer, where a majority of the engrafted cells were positive for vimentin. The transplantation significantly accelerated gastric ulcer healing compared with controls. The engrafted MSCs also expressed VEGF and HGF. Administration of anti-VEGF neutralizing antibody dose dependently reduced the MSC-induced promotion of ulcer healing. In conclusion, MSC transplantation accelerated gastric ulcer healing, possibly through the induction of angiogenesis in the gastric mucosa via the secretion of VEGF. The beneficial effects of MSCs might be mediated not only by their differentiation into gastric interstitial cells, but also by their ability to supply angiogenic factors.

scholarly journals Propolis and Its Gastroprotective Effects on NSAID-Induced Gastric Ulcer Disease: A Systematic Review

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3169
Author(s):  
Porfirio Alonso Ruiz-Hurtado ◽  
Leticia Garduño-Siciliano ◽  
Pilar Domínguez-Verano ◽  
Daniela Balderas-Cordero ◽  
Gustavo Gorgua-Jiménez ◽  
...  
Keyword(s):  
Gastric Ulcer ◽  
Public Health Problem ◽  
Good Alternative ◽  
Gastric Ulcers ◽  
Major Public Health Problem ◽  
Gastroprotective Activity ◽  
Future Studies ◽  
Ulcer Disease ◽  
Potential Use ◽  
Different Doses

Gastric ulcer disease induced by the consumption of NSAIDs is a major public health problem. The therapy used for its treatment causes adverse effects in the patient. Propolis is a natural product that has been used for the treatments of different diseases around the world. Nevertheless, there is little information about the activity of propolis in gastric ulcers caused by treatment with NSAIDs. Therefore, this review evaluates and compares the gastroprotective potential of propolis and its function against NSAID-induced gastric ulcers, for which a systematic search was carried out in the PubMed and ScienceDirect databases. The main criteria were articles that report the gastroprotective activity of propolis against the damage produced by NSAIDs in the gastric mucosa. Gastroprotection was related to the antioxidant, antisecretory, and cytoprotective effects, as well as the phenolic compounds present in the chemical composition of propolis. However, most of the studies used different doses of NSAIDs and propolis and evaluated different parameters. Propolis has proven to be a good alternative for the treatment of gastric ulcer disease. However, future studies should be carried out to identify the compounds responsible for these effects and to determine their potential use in people.

scholarly journals GASTROPROTECTIVE ACTIVITY OF SESAME (SESAMUM INDICUM) SEEDS EXTRACT IN ALENDRONATE-INDUCED GASTRIC ULCER IN RATS

2019 ◽  
pp. 214-217
Author(s):  
SHUBANGEE MISHRA ◽  
BALAJI O ◽  
VANISHREE RAO ◽  
SHALINI ADIGA
Keyword(s):  
Gastric Ulcer ◽  
Wistar Rats ◽  
Sesame Seed ◽  
Saline Group ◽  
Gastric Ulcers ◽  
Peptic Ulcers ◽  
Protective Effects ◽  
Gastroprotective Activity ◽  
Group 5 ◽  
Group 2

Objectives: Bisphosphonates are known to cause gastritis and only few studies have evaluated the use of plant extracts in the treatment of bisphosphonate induced peptic ulcers. In the present study, we examined the effect of sesame seed extract in the alendronate-induced gastric ulcer in adult Wistar rats. Methods: Thirty adult Wistar rats (180–250 g) of both sexes, divided into five groups (n=6) were used: Group 1 (vehicle control) – 0.9% saline, Group 2 (ulcer control) – alendronate 60 mg/kg, Group 3 (standard) – alendronate 60 mg/kg + pantoprazole 30 mg/kg/day, Group 4 (test groups) – alendronate 60 mg/kg + sesame 0.5 mg/kg, and Group 5 (test groups) – alendronate 60 mg/kg + sesame 1 mg/kg. All drugs were given orally once daily for 7 days except for alendronate given only on day 1. On day 8, rats were sacrificed, and stomach tissues were analyzed macroscopically for ulcers. Estimation of gastric pH, acidity, and volume was done along with mucin content measurement. One-way ANOVA followed by Tukey’s post hoc test was used for statistical analysis with p<0.05 taken as significant. Results: Our study found that sesame extract given therapeutically at doses of 0.5 and 1 mg/kg showed comparable results with that of pantoprazole 30 mg/kg. Both the doses of sesame, 0.5 and 1 mg/kg showed similar gastroprotective activity against alendronate-induced gastric ulcers in Wistar rats. Conclusion: The findings of this study clearly demonstrated the protective effects of Sesame against alendronate-induced gastric ulceration.

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