Efficacy and Safety of Novel Aspirin Formulations: A Randomized, Double-Blind, Placebo-Controlled Study

Low-dose aspirin represents the best option in the secondary prevention of coronary artery disease, but its extensive use in primary prevention is limited by the occurrence of gastric mucosal lesions and increased risk of bleeding. We investigated the safety profile of a novel sublingual aspirin formulation in 200 healthy volunteers, randomly assigned to ten (n = 20 each) different 7-day once-daily treatment regimens. Gastric mucosal injury based on the modified Lanza score (MLS), the histopathology of gastric mucosa and the serum determination of thromboxane B2 (TXB2) and urinary 11-dehydro-TXB2 levels were evaluated at basal as well as after 7 days of each placebo or aspirin treatment regimen. In Groups A and B (placebo—oral and sublingual, respectively), no changes in MLS and in gastric mucosal micro-vessel diameter were found at day 7. In contrast, in Groups C and D (oral standard aspirin—100 and 50 mg daily, respectively), the median MLS was significantly increased. Very few changes were found in Groups E and F (standard sublingual aspirin—100 and 50 mg, respectively). Groups G and H (oral administration of micronized collagen-cogrinded aspirin) showed gastric protection compared to Groups C and D. Moreover, Groups I and L (sublingual collagen-cogrinded aspirin—100 and 50 mg, respectively) showed a significant reduction (Group I) or total abolition (Group L) of gastric mucosal lesions and no difference compared to the standard one in serum TXB2 and urinary 11-dehydro-TXB2 levels. In conclusion, our data show that the new formulation leads to a better safety profile compared to standard aspirin, representing a better therapeutic option for extended use in primary and secondary prevention of cardiovascular diseases.

Helicobacter pylori Infection in Geriatric Patients: Current Situation and Treatment Regimens

Helicobacter pylori (H. pylori) has so far infected more than half the global population. It is the most important and controllable risk factor for gastric cancer. The elderly, who are at a higher incidence of the infection, are also commonly found to develop antibiotic resistance. The symptoms, diagnosis, clinical features (of gastric or extra-digestive diseases), and treatment of H. pylori infection in the elderly, are different from that in the non-elderly. Health conditions, including comorbidities and combined medication have limited the use of regular therapies in elderly patients. However, they can still benefit from eradication therapy, thus preventing gastric mucosal lesions and gastric cancer. In addition, new approaches, such as dual therapy and complementary therapy, have the potential to treat older patients with H. pylori infection.

Effect of a Cytoprotective Dose of Dehydroleucodine, Xanthatin, and 3-Benzyloxymethyl-5H-furan-2-one on Gastric Mucosal Lesions Induced by Mast Cell Activation

The aim of this study was to determine whether the lactones dehydroleucodine, xanthatin and 3-benzyloxymethyl-5H-furan-2-one, would be effective in an animal model of gastric ulcer induced by mast cell activation. Rats were divided into ten groups. Treatments were repeated for four days. The degree of gastric erosion was assessed with a scoring system and histological preparations. Gastric mast cell morphology was analyzed by histological procedures. Serum serotonin levels were determined as markers of mast cell activation. Statistical analyses were done using ANOVA and Tukey–Kramer test. We demonstrated that the repeated administration of compound 48/80 results in extensive mucosal lesions in the gastric mucosa and that such lesions occurred in association with mast cell degranulation and a significant increase of serum serotonin. We showed that these lesions were prevented by dehydroleucodine, xanthatin, and 3-benzyloxymethyl-5H-furan-2-one and that this effect was similar to that obtained with sodium cromoglycate. In conclusion, the results of the present study indicate that the optimal gastric cytoprotective dose of dehydroleucodine, xanthatin, and 3-benzyloxymethyl-5H-furan-2-one is efficacious in an animal model of gastric ulcer induced by mast cell activation. Our findings suggest that these lactones could be valuable tools for designing novel therapeutic agents for digestive disorders associated with inappropriate mast cell activation.

Antiulcer Potential of Olea europea L. cv. Arbequina Leaf Extract Supported by Metabolic Profiling and Molecular Docking

Gastric ulceration is among the most serious humanpublic health problems. Olea europea L. cv. Arbequina is one of the numerous olive varieties which have scarcely been studied. The reported antioxidant and anti-inflammatory potential of the olive plant make it a potential prophylactic natural product against gastric ulcers. Consequently, the main goal of this study is to investigate the gastroprotective effect of Olea europea L. cv. Arbequina leaf extract. LC-HRMS-based metabolic profiling of the alcoholic extract of Olea europea L. cv. Arbequina led to the dereplication of 18 putative compounds (1–18). In vivo indomethacin-induced gastric ulcer in a rat model was established and the Olea europea extract was tested at a dose of 300 mg kg−1 compared to cimetidine (100 mg kg−1). The assessment of gastric mucosal lesions and histopathology of gastric tissue was done. It has been proved that Olea europea significantly decreased the ulcer index and protected the mucosa from lesions. The antioxidant potential of the extract was evaluated using three in vitro assays, H2O2 scavenging, xanthine oxidase inhibitory, and superoxide radical scavenging activities and showed promising activities. Moreover, an in silico based study was performed on the putatively dereplicated compounds, which highlighted that 3-hydroxy tyrosol (4) and oleacein (18) can target the 5-lipoxygenase enzyme (5-LOX) as a protective mechanism against the pathogenesis of ulceration. Upon experimental validation, both compounds 3-hydroxy tyrosol (HT) and oleacein (OC) (4 and 18, respectively) exhibited a significant in vitro 5-LOX inhibitory activity with IC50 values of 8.6 and 5.8 µg/mL, respectively. The present study suggested a possible implication of O. europea leaves as a potential candidate having gastroprotective, antioxidant, and 5-LOX inhibitory activity for the management of gastric ulcers.

Antiulcer and Antioxidant Potential of Eucalyptus camaldulensis Leaves Methanol Extract in Albino Rats

Aim: This research is aimed at assessing the antiulcer and antioxidant potential of Eucalyptus camaldulensis leaves methanol extract in albino rats. Methodology: Fresh leaves of Eucalyptus camaldulensis were harvested from the Department of Plant Science and Biotechnology, Kebbi State University of Science and Technology, Aliero. The dried pulverized leaves were extracted using Soxhlet apparatus with methanol as the solvent. Thirty male albino rats weighing between 200 g and 250 g were used in this study. The rats were randomly divided into six (6) groups of five (5) rats each. Antiulcer and antioxidant activity was evaluated using ethanol-induced ulcer model. Ulcer was induced in all groups except Group 1 which served as the control and received distilled water only. Group 2 was not treated while Group 3 was treated with omeprazole (50mg/kg). Groups 4, 5 and 6 were treated with 200mg/kg, 400mg/kg and 800mg/kg of the extract respectively. After seven days of treatment, the albino rats were humanely sacrificed, ulcer index determined and the serum assessed for antioxidants levels. Results: The gastric mucosal lesions produced in the untreated group were very visible and had an ulcer index of 12.83. Pre-treatment with omeprazole and graded doses of the extract showed significant reductions (P<.05) in ulcer index in a dose dependent manner. The SOD, CAT, GPx, GSH and MDA levels were significantly reduced (P<.05) in the untreated group with progressive reduction in the treated groups as the extract concentration reduced. The antioxidant vitamins (Vitamin A, C and E) reduced in concentration significantly (P<.05) without any significant difference between the untreated group and the groups that received 200mg/kg and 400mg/kg of the extract. Meanwhile, the group treated with 800mg/kg of the extract significantly increased (P<.05) the concentrations of these vitamins when compared to the group that received ethanol only. Conclusion: Eucalyptus camaldulensis leaves methanol extract possesses both antiulcer and antioxidant activity. This justifies the use of Eucalyptus camaldulensis leaves in traditional medicine in the management of ulcer and validates its antiulcer potential.

Protective Effect of Pyrus ussuriensis Maxim. Extract against Ethanol-Induced Gastritis in Rats

Pyrus ussuriensis Maxim (Korean pear) has been used for hundreds of years as a traditional herbal medicine for asthma, cough, and atopic dermatitis in Korea and China. Although it was originally shown to possess anti-inflammatory, antioxidant, and antiatopic properties, its gastroprotective effects have not been investigated. In the present study, we evaluated the protective effects of Pyrus ussuriensis Maxim extract (PUE) against ethanol-induced gastritis in rats. The bioactive compound profile of PUE was determined by gas chromatography mass spectroscopy (GC-MS) and high-performance liquid chromatography (HPLC). The gastroprotection of PUE at different doses (250 and 500 mg/kg body weight) prior to ethanol ingestion was evaluated using an in vivo gastritis rat model. Several endpoints were evaluated, including gastric mucosal lesions, cellular degeneration, intracellular damage, and immunohistochemical localization of leucocyte common antigen. The gastric mucosal injury and ulcer score were determined by evaluating the inflamed gastric mucosa and by histological examination. To identify the mechanisms of gastroprotection by PUE, antisecretory action and plasma prostaglandin E2 (PGE2), gastric mucosal cyclic adenosine monophosphate (cAMP), and histamine levels were measured. PUE exhibited significant antioxidant effects with IC50 values of 56.18 and 22.49 µg/mL for 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′- azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) inhibition (%), respectively. In addition, GC/MS and HPLC analyses revealed several bioactive compounds of PUE. Pretreatment with PUE significantly (P < 0.05) decreased the ulcer index by preventing gastric mucosal lesions, erosion, and cellular degeneration. An immunohistochemical analysis revealed that PUE markedly attenuated leucocyte infiltration in a dose-dependent manner. The enhancement of PGE2 levels and attenuation of cAMP levels along with the inhibition of histamine release following PUE pretreatment was associated with the cytoprotective and healing effects of PUE. In contrast, the downregulation of the H+/K+ ATPase pathway as well as muscarinic receptor (M3R) and histamine receptor (H2R) inhibition was also involved in the gastroprotective effects of PUE; however, the expression of cholecystokinin-2 receptors (CCK2R) was unchanged. Finally, no signs of toxicity were observed following PUE treatment. Based on our results, we conclude that PUE represents an effective therapeutic option to reduce the risk of gastritis and warrants further study.

Feasibility of Standardized Procedures of White Light Gastroscopy for Clinical Practice: A Multiple Center Study in China

Background: There is no standardized operation procedure for white light gastroscopy (WLG）in China. We aimed to established a standardized procedure of white light gastroscopy for clinic patients screening, to verify its effect and its feasibility in clinical practice. Methods: We applied the standardized procedure for WLG to out-patients at 9 tertiary hospitals in Beijing. All of the clinical information and operation procedure were recorded.Results: We set a standardized operation procedure for WLG. 1051 patients were enrolled in the base-line survey stage between March 2014 and December 2015. 2156 patients were enrolled in the WLG standardized operation stage from January 2016 to June 2017. The median durations of standardized procedure group were significantly longer than that of the base-line group (prolonged 60.3 seconds averagely, P=0.003). The taken picture numbers in the standardized procedure group were significantly higher than that in the base-line group (17 pictures more averagely, P<0.001). The overall detection rate of gastric mucosal lesions in the standardized procedure group was significantly higher than that in the base-line group (52.5% vs. 38.4%, P<0.01). Both the patient and endoscopist satisfaction scores in the standardized procedure group were all significantly improved than those in the base-line group.Conclusions: The standardized procedure for WLG can improve the detection rate of gastric lesions significantly, and also improve the satisfaction of patients and endoscopists despite prolonged duration. The standardized procedure for white light gastroscopy is effective and feasible in clinical practice with the present endoscopy equipment in China.