Efficacy of the oral supplement, Equine Omega Complete, for the prevention of gastric ulcers and alpha-tocopherol supplementation in horses.

BACKGROUND: Omega-3 fatty acid and alpha-tocopherol supplementation reduces gastric ulcer formation in humans and rodents; however, efficacy of prevention in horses is unknown. Equine Omega Complete (EOC) is an oral supplement containing omega-3 fatty acids and alpha-tocopherol. HYPOTHESIS/OBJECTIVE: Determine if EOC supplementation prevents gastric ulcers and increases serum alpha-tocopherol concentrations in healthy horses. ANIMALS: Nine thoroughbred geldings; 5-13 years old. METHODS: Prospective randomized block design, repeated in crossover model. Horses were administered EOC, omeprazole, or water PO for 28 days. Horses underwent an established gastric ulcer induction protocol from days 21-28 via intermittent feed deprivation. Gastroscopies were performed on days 0, 21, and 28. Serum alpha-tocopherol concentrations were measured on days 0 and 28. The effects of treatment and time on ulcer grades were assessed with ordinal logistic regression, with significance at P-value <.05. RESULTS: Ulcer grades increased during ulcer induction in control and EOC but not omeprazole groups (P = .02). Grades increased in EOC-treated horses after ulcer induction from a median of 1 [95% confidence interval 0-2.5] (day 0) to 2.5 [1.5-3.5] (day 28) and were similar to the control group (P = .54). Serum alpha-tocopherol increased in EOC-treated horses from day 0 to day 28 (mean 2.2 ± 0.43 µg/mL to 2.96 ± 0.89 µg/mL; P < .001) with high individual variation; this increase was not different from omeprazole or control groups. CONCLUSION AND CLINICAL IMPORTANCE: Supplementation with EOC for 28 days did not prevent gastric ulcer formation nor increase alpha-tocopherol concentrations relative to the control group.

Formulation, optimization and characterization of allantoin-loaded chitosan nanoparticles to alleviate ethanol-induced gastric ulcer: in-vitro and in-vivo studies.

Allantoin (ALL) is a phytochemical possessing an impressive array of biological activities. Nonetheless, developing a nanostructured delivery system targeted to augment the gastric antiulcerogenic activity of ALL has not been so far investigated. Consequently, in this survey, ALL-loaded chitosan/sodium tripolyphosphate nanoparticles (ALL-loaded CS/STPP NPs) were prepared by ionotropic gelation technique and thoroughly characterized. A full 24 factorial design was adopted using four independently controlled parameters (ICPs). Comprehensive characterization, in vitro evaluations as well as antiulcerogenic activity study against ethanol-induced gastric ulcer in rats of the optimized NPs formula were conducted. The optimized NPs formula, (CS (1.5% w/v), STPP (0.3% w/v), CS:STPP volume ratio (5:1), ALL amount (13 mg)), was the most convenient one with drug content of 6.26 mg, drug entrapment efficiency % of 48.12%, particle size of 508.3 nm, polydispersity index 0.29 and ζ-potential of + 35.70 mV. It displayed a sustained in vitro release profile and mucoadhesive strength of 45.55%. ALL-loaded CS/STPP NPs (F-9) provoked remarkable antiulcerogenic activity against ethanol-induced gastric ulceration in rats, which was accentuated by histopathological, immunohistochemical (IHC) and biochemical studies. In conclusion, the prepared ALL-loaded CS/STPP NPs could be presented to the phytomedicine field as an auspicious oral delivery system for gastric ulceration management.

Hesperidin protects against stress induced gastric ulcer through regulation of peroxisome proliferator activator receptor gamma in diabetic rats.

Stress induced gastric ulcer is a serious health problem in diabetic patients. Some studies reported that hesperidin (HDN), a citrus bioflavonoid, can bind to and stimulate peroxisome proliferator-activator receptor-gamma (PPAR-γ) which may mediate its antidiabetic, anti-inflammatory and anti-oxidant effects. This work aims to study the possible protective effect of HDN against stress induced gastric ulcer in diabetic rats as well as the possible involvement of PPARγ in this effect. Type 2 diabetes was induced using streptozotocin and nicotinamide. Diabetic rats received either HDN (100 mg/kg/day, orally) & omeprazole (20 mg/kg/day, orally) or HDN (100 mg/kg/day, orally) + GW9662, PPARγ antagonist, (1 mg/kg/day, i.p.) for 8 weeks then acute gastric injury was induced by cold restraint stress technique. Glycemic controls and gastroprotective effects were evaluated by measuring serum levels of glucose and insulin, gastric free and total acidity and gastric ulcer indices. Histopathological examination of gastric mucosa was also performed. To determine the underlying mechanism of action, gastric mucosal expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), hemeoxygenase-1 (HO-1), cluster of differentiation 45 (CD45), cyclooxygenase-2 (COX-2), nuclear factor kappa B (NFκB) and inducible nitric oxide synthase (iNOS), gastric contents of reduced glutathione (GSH), malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α) and nitric oxide (NO); as well as superoxide dismutase (SOD) and catalase activities were measured. HDN significantly improved glycemic level; it also reduced gastric acidity and gastric ulcer index and histopathological changes comparable to that produced by omeprazole. Moreover, HDN reduced lipid peroxidation and inflammatory markers levels and enhanced antioxidant capacity. The use of GW9662 significantly abrogated the gastric protective effect of HDN as well as reduced the antioxidant and anti-inflammatory effects. Our work showed, for the first time that, HDN has promising protective effect against stress induced gastric ulcer in diabetic rats through activation of PPARγ.

Comorbid for gastroduodenal ulcers in the aspect of calcium imbalance and blockers of slow calcium channels in their treatment.

AIM: Find out the calcium content of the blood reflecting its balance and functional status the calcium regulatory system when it is comorbid for gastroduodenal ulcers (GDU), developed on the background of chronic erosive gastritis (CEG), chronic erosive duodenitis (CED), arterial hypertension (AH) and osteo-articular pathology with the use of nonsteroidal anti-inflammatory drugs (NSAIDs), and the impact of his changes on the activity ulzerogennogo process, the state of regional microcirculation and the functions of the stomach. To determine the pathogenetic justification for and effectiveness of blockers of slow calcium channels (BSCaC) in complex treatment. MATERIALS AND METHODS: Examined 132 patients with GDU. All patients were divided into groups: the 1st (n=49) - patients with recurrent of peptic ulcer disease (PUD) and CEG/CED; the 2nd (n=23) - with recurrence of PUD and AH, the 3rd (n=14) - with GDU and osteoarticular pathology, taking NSAIDs. Patients of these three groups for the treatment of erosive ulcerous lesions of gastroduodenal zone (GDZ) has been appointed complex therapy with inclusion of nifedipine. The 4th (control) group consisted of 56 patients with recurrent BU without concomi- tant pathology, applying integrated therapy with nifedipine. RESULTS: The PU relapse, comorbid her over with erosive gastroduodenitis, hypertension, GDU with of osteoarticular pathology and taking NSAIDs is accompanied by a calcium imbalance with increased levels of calcium in the blood, contributing to increase of acid-peptic factor in the formation of hypermotor dyskinesia stomach, disruption of regional microcirculation and repair processes, activa- tion of ulcerogenesis in GDZ. Inclusion in the complex therapy of GDU of nifedipine leads to the recovery of calcium balance, functions of the stomach and regional mi- crocirculation, accelerates the timing and increases the percentage of scarring ulcers. CONCLUSION: GDU accompanied by dysfunction the calcium regulatory system with increasing levels of blood calcium, contributing to the for- mation of the major pathogenetic mechanisms of ulcerogenesis. BSCaC application in complex therapy of GDU is pathogenetically justified and clinically effective, reduces the excessive drug treatment in the treatment.

Suppressive effect of Spirulina fusiformis on diclofenac-induced hepato-renal injury and gastrointestinal ulcer in Wistar albino rats: A biochemical and histological approach.

CONTEXT: The non-steroidal anti-inflammatory drug (NSAID), diclofenac causes hepato-renal toxicity and gastric ulcer. The aim of this study was to investigate the protective effect of Spirulina fusiformis on Diclofenac-induced toxicity in Wistar albino rats. METHODS: Rats were treated as follows: normal control (group I); diclofenac (50mg/kgb.w., i.p.) treated rats (group II); diclofenac-induced (50mg/kgb.w., i.p.) rats treated with Spirulina fusiformis (400mg/kgb.w., p.o.) (group III); diclofenac-induced (50mg/kgb.w., i.p.) rats treated with silymarin (25mg/kgb.w., p.o.) (group IV); Spirulina fusiformis (400mg/kgb.w., p.o.) alone treated rats (groupV). Biochemical (liver and kidney functional markers) and antioxidant parameters (enzymic and non-enzymic antioxidants) were measured in the blood and tissue homogenates of the rats. Evaluation of intestinal ulcer score and assessment of liver and kidney histology were also done. DISCUSSION: Alterations in the levels of biochemical and antioxidant assays and histopathological changes in liver and kidney proved the toxic effect of diclofenac. The ulcer score was significantly increased in the diclofenac treated rats. Spirulina fusiformis showed to reduce such changes and was able to restore normal antioxidant status in the rats. CONCLUSION: Our study proves the hepato-renal and gastroprotective activity of Spirulina fusiformis in diclofenac-treated rats.

Interaction of lafutidine in binding to human serum albumin in gastric ulcer therapy: STD-NMR, WaterLOGSY-NMR, NMR relaxation times, Tr-NOESY, molecule docking, and spectroscopic studies.

In this study, lafutidine (LAF) was used as a model compound to investigate the binding mechanism between antiulcer drugs and human serum albumin (HSA) through various techniques, including STD-NMR, WaterLOGSY-NMR, (1)H NMR relaxation times, tr-NOESY, molecule docking calculation, FT-IR spectroscopy, and CD spectroscopy. The analyses of STD-NMR, which derived relative STD (%) intensities, and WaterLOGSY-NMR, determined that LAF bound to HSA. In particular, the pyridyl group of LAF was in close contact with HSA binding pocket, whereas furyl group had a secondary binding. Competitive STD-NMR and WaterLOGSY-NMR experiments, with warifarin and ibuprofen as site-selective probes, indicated that LAF preferentially bound to site II in the hydrophobic subdomains IIIA of HSA. The bound conformation of LAF at the HSA binding site was further elucidated by transferred NOE effect (tr-NOESY) experiment. Relaxation experiments provided quantitative information about the relationship between the affinity and structure of LAF. The molecule docking simulations conducted with AutoDock and the restraints derived from STD results led to three-dimensional models that were consistent with the NMR spectroscopic data. The presence of hydrophobic forces and hydrogen interactions was also determined. Additionally, FT-IR and CD spectroscopies showed that LAF induced secondary structure changes of HSA.

Role of curcumin in protection of gastric mucosa against stress-induced gastric mucosal damage. Involvement of hypoacidity, vasoactive mediators and sensory neuropeptides.

The antioxidizing properties of curcumin, a highly pleiotropic substance used for centuries in traditional medicine has been confirmed by numerous experimental and clinical studies. Curcumin exhibits anti-inflammatory, antiproliferative and anti-angiogenic actions inhibiting the development and progression of tumors but the efficacy of this compound to influence gastric acid secretion n in the stomach and to affect the gastric mucosal damage induced by non-topical ulcerogenes such as stress has been little studied. We determined the effect of curcumin on basal and pentagastrin- or histamine-stimulated gastric secretion, in rats with surgically implemented gastric fistulas and we assessed the contribution of gastric secretion, endogenous prostaglandin (PG), endogenous nitric oxide (NO), as well as sensory afferent nerves in the mechanisms underlying the potential gastroprotective effects of curcumin against stress-induced gastric mucosal lesions. Rats exposed to water immersion and restraint stress (WRS) for 3.5 h were pretreated either with: 1) vehicle (saline); 2) curcumin (2.5 - 100 mg/kg i.g.) or 3) curcumin (50 mg/kg i.g.) combined with or without indomethacin (5 mg/kg i.p.), SC-560 (5 mg/kg i.g.) or rofecoxib (10 mg/kg i.g.); 4) curcumin (50 mg/kg i.g.) co-administered with (L-NNA (20 mg/kg i.p.) with or without L-arginine (200 mg/kg i.g.), a substrate for NO-synthase; 5) curcumin (50 mg/kg i.g.) administered in rats with intact or capsaicin-induced functional ablation of sensory nerve fibers, and 6) curcumin (50 mg/kg i.g.) administered with capsazepine (5 mg/kg i.g.), the antagonist of vanilloid TRPV1 receptor. The number of gastric lesions was determined by planimetry, the gastric blood flow (GBF) was assessed by H2-gas clearance technique, the plasma gastrin concentrations were measured using the radioimmunoassay (RIA) and the expression of mRNA for tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in gastric mucosa was evaluated by reverse transcription polymerase chain reaction (RT-PCR). Curcumin dose-dependently reduced the WRS-induced gastric lesions, the dose inhibiting these lesions by 50% being about 50 mg/kg. These effects of curcumin were accompanied by an increase in GBF and the reduction in basal and histamine- or pentagastrin-stimulated gastric acid secretion. The protective and hyperemic activities of curcumin (50 mg/kg i.g.) against WRS lesions were significantly attenuated (P < 0.05) in rats pretreated with rofecoxib and SC-560 and completely reversed (P < 0.01) by indomethacin. L-NNA significantly reduced (P < 0.05) the decrease in WRS-induced lesions and the accompanying rise in GBF caused by curcumin and these effects were restored by concurrent treatment with L-arginine (200 mg/kg i.g.). The curcumin-induced decrease in the number of WRS-induced gastric lesions and accompanying increase in the GBF were significantly attenuated (P < 0.05) in capsaicin-denervated rats and in those pretreated with capsazepine. These effects of curcumin in rats with capsaicin denervation were restored by concomitant treatment with exogenous calcitonin gene related pepetide (CGRP) combined with curcumin and subsequently exposed to WRS. The expression of mRNA for TNF-α, COX-2 and iNOS was significantly increased (P < 0.05) in vehicle-pretreated control rats exposed to WRS and significantly attenuated (P < 0.05) by curcumin administered in graded dosages. We conclude that curcumin exerts gastroprotective and hyperemic activities against experimental stress-induced gastric lesions by mechanism involving endogenous prostaglandins, NO, the neuropeptides such as CGRP released from capsaicin-sensitive afferent nerves and the activation of vanilloid TRPV1 receptors located on these sensory nerve terminals.

Gastro-protective and Anti-stress Efficacies of Monomethyl Fumarate and a Fumaria indica Extract in Chronically Stressed Rats.

Results of the very first experiments conducted to evaluate therapeutic potentials of a fumarate containing Fumaria indica extract and of fairly low daily oral doses of monomethyl fumarate for prevention of chronic unavoidable foot-shock stress-induced gastric ulcers, and possible involvement of diverse neuro-hormonal and oxidative process in their stress response desensitizing effects are reported and discussed in this article. Preventive effects of 21 daily oral 60, 120, and 240 mg/kg doses of a standardized 50 % methanolic F. indica extract (MFI) and 1.25, 2.50, and 5.00 mg/kg/day of pure monomethyl fumarate (MMF) were compared in rats subjected to one hour daily unavoidable foot-shocks. A pharmaceutically well-standardized Withania somnifera (WS) root extract was used as a reference herbal anti-stress agent in all experiments. Effects of the treatments on stress-induced alterations in body weight, adrenal and spleen weights, gastric ulcer and ulcer index, weight of glandular stomach, protective mucosal glycoprotein content, cellular proliferation, oxidative stress on stomach fundus, and brain tissues of male rats were quantified. Other parameters quantified were plasma corticosterone levels, brain monoamine levels, and expressions of the cytokines TNF-α, IL-10, and IL-1ß in blood and brain of stressed and treated rats. Most but not every observed stress-induced anomalies were suppressed or completely prevented by both MFI and pure MMF treatments in dose-dependent manner. Qualitatively, the observed activity profiles of both of them were similar to those of WS dose tested. These results reveal that both MFI and MMF are potent gastro-protective agents against chronic unavoidable stress-induced ulcers and strongly suggest that they act as regulators or modulators of monoamine, corticosterone, and cytokine homeostasis.

Preparation and Pharmacological Evaluation of Novel Orally Active Ester Prodrugs of Ketoprofen with Non-Ulcerogenic Property.

This study investigates anti-inflammatory activity with improved pharmacokinetic and non-ulcerogenic properties of various novel synthesized prodrugs of ketoprofen in experimental animals. Prodrugs 3a, 3f and 3k were found to possess significant anti-inflammatory activity with almost non-ulcerogenic potential than standard drug ketoprofen (1) in both normal and inflammation-induced rats. The experimental findings elicited higher AUC and plasma concentration at 1 and 2 h indicating improved oral bioavailability as compared to parent drug ketoprofen. These prodrugs are found to have no gastric ulceration with retained anti-inflammatory activity. Therefore, present experimental findings demonstrated significant improvement of various pharmacokinetic properties with non-ulcerogenic potential of ester prodrugs of ketoprofen.

Anti-Ulcerogenic Properties of Lycium chinense Mill Extracts against Ethanol-Induced Acute Gastric Lesion in Animal Models and Its Active Constituents.

The objective of this study was to explore the gastroprotective properties of the aerial part of Lycium chinense Mill (LCA) against ethanol-induced gastric mucosa lesions in mice models. Administration of LCA at doses of 50, 100, 200 and 400 mg/kg body weight prior to ethanol consumption dose dependently inhibited gastric ulcers. The gastric mucosal injury was analyzed by gastric juice acidity, glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), myeloperoxidase (MPO) activities. Furthermore, the levels of the inflammatory mediators, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) in serum were also analyzed using ELISA. Pathological changes were also observed with the aid of hematoxylin-eosin (HE) staining. Our results indicated that LCA significantly reduced the levels of MPO, MDA and increased SOD and GSH activities. Furthermore, LCA also significantly inhibited the levels of TNF-α, IL-6, and IL-1ß in the serum of ulcerated mice in a dose dependent manner. Immunohistological analysis indicated that LCA also significantly attenuated the overexpression of nuclear factor-κB in pretreated mice models. This findings suggests Lycium chinense Mill possesses gastroprotective properties against ethanol-induced gastric injury and could be a possible therapeutic intervention in the treatment and management of gastric ulcers.

Mangiferin Mitigates Gastric Ulcer in Ischemia/ Reperfused Rats: Involvement of PPAR-γ, NF-κB and Nrf2/HO-1 Signaling Pathways.

Mangiferin (MF), a xanthonoid from Mangifera indica, has been proved to have antisecretory and antioxidant gastroprotective effects against different gastric ulcer models; however, its molecular mechanism has not been previously elucidated. Therefore, the aim of this study was to test its modulatory effect on several signaling pathways using the ischemia/reperfusion model for the first time. Animals were treated with MF, omeprazole (OMP), and the vehicle. The mechanistic studies revealed that MF mediated its gastroprotective effect partly via inducing the expression of Nrf2, HO-1 and PPAR-γ along with downregulating that of NF-κB. Surprisingly, the effect of MF, especially the high dose, exceeded that mediated by OMP except for Nrf2. The molecular results were reflected on the biomarkers measured, where the antioxidant effect of MF was manifested by increasing total antioxidant capacity and glutathione, besides normalizing malondialdehyde level. Additionally, MF decreased the I/R-induced nitric oxide elevation, an effect that was better than that of OMP. In the serum, MF, dose dependently, enhanced endothelial nitric oxide synthase, while reduced the inducible isoform. Regarding the anti-inflammatory effect of MF, it reduced serum level of IL-1ß and sE-selectin, effects that were mirrored on the tissue level of myeloperoxidase, the neutrophil infiltration marker. In addition, MF possessed an antiapoptotic character evidenced by elevating Bcl-2 level and reducing that of caspase-3 in a dose related order. As a conclusion, the intimated gastroprotective mechanisms of MF are mediated, partially, by modulation of oxidative stress, inflammation and apoptosis possibly via the Nrf2/HO-1, PPAR-γ/NF-κB signaling pathways.

Anti-ulcerogenic effect of Zuojin Pill against ethanol-induced acute gastric lesion in animal models.

ETHNOPHARMACOLOGICAL RELEVANCE: Zuojin Pill (ZJP), a traditional Chinese medicinal decoction, contains two herbal drugs: Coptis chinensis Franch. and Tetradium ruticarpum (A. Juss.) Hartley in the ratio of 6:1 (w/w). In this study, ZJP was evaluated for its gastroprotective potential against mucosal lesions induced by ethanol in mice. MATERIALS AND METHODS: 50 mice were assigned to 5 groups: groups 1 and 2 were given distilled water orally. Group 3 was administered omeprazole 20mg/kg, groups 4 and 5 were given ZJP (1g/kg, 2g/kg, respectively). After an additional hour, the mice in groups 2-5 received ethanol (0.2ml/kg) orally while group 1 received distilled water instead. Mice were killed after 4h and their serum and stomachs subjected to further studies. The superoxidase dismutase (SOD) activities and malondialdehyde (MDA) level in serum were assayed by SOD and MDA kits, respectively. The myeloperoxidase (MPO) activities in stomachs were assayed by MPO kit. The levels of inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) in serum were assayed by enzyme-linked immunosorbent assay method (ELISA). Pathological changes were observed by hematoxylin-eosin (HE) staining. The levels of nuclear factor-кBp65 (NF-кBp65), P-NF-кBp65, P-IкBα, IкBα, P-IKKα, IKKα, P-IKKß, IKKß in stomachs were assayed by western blot. RESULTS: The data showed that treatment with the ZJP markedly attenuated MPO, MDA, TNF-α, IL-6, IL-1ßand increased SOD; and ZJP also decreased protein levels of P-NF-кBp65, P-IкBα, P-IKKαand P-IKKßin gastric stomachs. CONCLUSION: It was concluded that ZJP may represents a potential therapeutic option to reduce the risk of gastric ulceration and the gastroprotective activity of ZJP might contribute in adjusting the inflammatory cytokine by regulating the NF-кB signaling pathway.

Comparison of the anti-ulcer activity between the crude and bran-processed Atractylodes lancea in the rat model of gastric ulcer induced by acetic acid.

ETHNOPHARMACOLOGICAL RELEVANCE: The rhizome of Atractylodes lancea (AL, Compositae, Chinese name: Cangzhu; Japanese name: Sou-ju-tsu) has been used traditionally for the treatment of various diseases such as digestive disorders, rheumatic diseases, and influenza in China, Korea and Japan. The crude AL and AL bran-processed are both listed in the Chinese Pharmacopoeia. However, the differences between the effects of the crude and AL bran-processed on gastric ulcer were poorly understood, and the mechanisms for the treatment of gastric ulcer were not clear. This study aimed at comparing the anti-ulcer effects between the crude AL and AL processed in acetic acid induced model in rats and evaluating the mechanisms of action involved in the anti-ulcer properties of AL. MATERIALS AND METHODS: The model of gastric ulcer was imitated by acetic acid in rats, and AL was gavaged. The serum and gastric tissues were collected. The levels of epidermal growth factor (EGF), trefoil factor2 (TFF2), tumor necrosis factor-α (TNF-α), interleukin 6, 8 (IL-6, 8) and prostaglandin E2 (PGE2) in serum and gastric tissues were determined by the double-antibody sandwich enzyme-linked immunosorbent assay (ELISA), and the mRNA expressions of EGF, TFF2, TNF-α, and IL-8 in stomach were analyzed by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Meanwhile, histopathological changes were evaluated by hematoxylin and eosin (HE) stain. The protein expressions of EGF, TFF2, TNF-α, and IL-8 were examined by immunohistochemistry in stomach. RESULTS: The results demonstrated that the damage of gastric tissue was obviously alleviated and the productions of TNF-α, IL-8, IL-6, and PGE2 and the mRNA expressions of TNF-α, and IL-8 were notably inhibited. Furthermore, the productions of EGF and TFF2 and the mRNA expressions of EGF and TFF2 were significantly stimulated by both crude AL and AL processed in a dose-dependent manner. Compared with the crude AL, the processed AL was more effective. CONCLUSION: The AL processed had more satisfactory effects in treatment of gastric-ulcer than the crude AL. The anti-ulcer effects of AL could be attributed to the anti-inflammatory properties via down-regulating TNF-α, IL-8, IL-6 and PGE2 and to the gastroprotective effects via up-regulating EGF and TFF2.

[Study on drug properties of components in Euodiae Fructus based on rat stress gastric ulcer model with cold syndrome].

OBJECTIVE: To clarify drug properties of components in Euodiae Fructus. METHOD: The rat cold syndrome model was induced by cold water stress method. The content of neurotransmitters sand hormones such as DA, 5-HT, NE, AChE and 17-OHCS in serum of model rats were taken as the indexes to evaluate drug properties of components in Euodiae Fructus. RESULT: Euodiae Fructus and its components could correct or relief the content of energy metabolism and substance metabolism-related neurotransmitters sand hormones in serum of model rats with water-stressed cold syndrome. CONCLUSION: Euodiae Fructus and its components are proved to show hot property.

Cytoprotective and antioxidant effects of the methanol extract of Eremomastax speciosa in rats.

BACKGROUND: Ethno-botanical information shows that Eremomastax speciosa is used in the traditional management of various stomach complaints including gastro-duodenal ulcers. MATERIALS AND METHODS: In this study, we tested the cytoprotective potential of the whole plant methanol extract (100-200 mg/kg, p.o), against HCl/ethanol, absolute ethanol, cold/restraint stress rats, and pylorus legated rats pre-treated with indomethacin. The effects of the extract on gastric lesion inhibition, the volume of gastric juice, gastric pH, gastric acid output, mucus production and gastric peptic activity were recorded. Oxidative stress parameters were measured in blood and gastric tissue samples obtained from the animals in all the models tested. RESULTS: The extract significantly (p<0.05), reduced the formation of cold/restraint ulcers by (31-60%, inhibition), completely inhibited (100%) the formation of lesions induced by HCl/ethanol at the highest dose, but was less effective against absolute ethanol (22-46% inhibition). The extract (200 mg/kg), significantly reduced lesion formation (P<0.01), gastric acidity (P<0.01), and volume of gastric secretions (P<0.05), in the indomethacin/pylorus ligation model, and did not affect the activity of pepsin in gastric juice. Blood concentrations of antioxidant enzymes (catalase, SOD and GSH), increased significantly and MDA concentrations decreased in all models tested. CONCLUSION: Cytoprotection by E. speciosa methanol extract was attributed to its ability to reduce acid secretion, and to enhance mucosal defence and in vivo antioxidant status.

Extraction optimization of carbohydrate compound from Huangqi using orthogonal design.

The effect of extraction time, extraction temperature and time on the yield of Huangqi carbohydrate compound (HQCC) was investigated using single factor and orthogonal experiment design. The influence by the parameters on the extraction yields of carbohydrate compound decreased in the order of: C (extraction number)>A (extraction time)>B (extraction temperature) according to the R values. Based on this analysis, and considering the carbohydrate compound extraction efficiency, the cost of energy and the feasibility of experiment, the optimum conditions of extraction were therefore determined as follows: extraction time 120min, extraction temperature 80°C, and extraction number 4. Oral administration of HQCC reduced lipid peroxidation level and enhanced antioxidant enzymes activities in gastric mucosa. In addition, HQCC reduced the serum IL-8 and TNF-α levels. In conclusion, these data reveal that HQCC promotes regeneration of damaged gastric mucosa, probably through its antioxidative mechanism.

Effect of selenium and grape seed extract on indomethacin-induced gastric ulcers in rats.

Indomethacin (IND) is a non-steroid anti-inflammatory agent that is known to induce severe gastric mucosal lesions. In this study, we investigated the protective effect of selenium (SEL), grape seed extract (GSE), and both on IND-induced gastric mucosal ulcers in rats. Sprague-Dawley rats (200-250 g) were given SEL, GSE, and both by oral gavage for 28 days, and then gastric ulcers were induced by oral administration of 25 mg/kg IND. Malondialdehyde (MDA), non-enzymatic (reduced glutathione, GSH) and enzymatic (superoxide dismutase, catalase, and glutathione peroxidase) antioxidants, prostaglandin E2 (PGE2) in gastric mucosa, and serum tumor necrosis factor alpha (TNF-α) were measured. Moreover, gastric ulcer index and preventive index were determined. Indomethacin increased the gastric ulcer index, MDA, TNF-α, and decreased PGE2 and non-enzymatic (GSH) and enzymatic (superoxide dismutase, catalase, and glutathione peroxidase) antioxidants. Pretreatment with SEL, GSE, and both significantly decreased the gastric ulcer index, MDA, and TNF and increased antioxidants and PGE2. Histopathological observations confirm the gastric ulcer index and biochemical parameters. Selenium and GSE have a protective effect against IND-induced gastric ulcers through prevention of lipid peroxidation, increase of GSH, activation of radical scavenging enzymes, PGE2 generation, and anti-inflammatory activity. Co-administration of GSE and SEL is more effective than GSE or SEL alone.

Comparison of the chemical composition and biological effects of the roots, branches and leaves of Heteropterys tomentosa A. Juss.

ETHNOPHARMACOLOGICAL RELEVANCE: HETEROPTERYS TOMENTOSA: A. Juss (Malpighiaceae), commonly mistaken as Heteropterys aphrodisiaca, is chronically used by the Brazilian population to improve general health due to its claimed protective effects against a wide range of medical conditions. AIM OF THE STUDY: This study in rodents aimed to verify the adaptogenic potential of the hydroalcoholic extracts of the roots (the most commonly used portion), branches and leaves of the plant. MATERIALS AND METHODS: The phytochemical constitution of the extracts was analyzed through thin-layer chromatography and high-performance liquid chromatography. Restriction- and cold-induced stress in rats treated for 14 days with 100 or 300 mg/kg of the extracts were used to evaluate parameters such as ulceration, adrenals, thymus and spleen weights, as well as ACTH and corticosterone plasmatic levels. The stress response also was evaluated in mice by self-analgesia induced by restraint stress, after 7 days of treatment at doses of 100 and 300 mg/kg. The learning and memory of aged rats treated with extracts of root or branches at the dose of 50 mg/kg for 80 days were evaluated in the elevated T-maze test. RESULTS: The chemical constituents of the three parts of the plant were relatively similar in the presence of saponins, hydrolysable tannins, flavonoids, polyphenols and triterpenes. None of the three extracts were capable of protecting the stomach from ulcerations in rats submitted to cold restraint stress or protecting from alterations in adrenal or spleen weight (p>0.05). Furthermore, the extracts did not inhibit increases in plasma levels of corticosterone and adrenocorticotropic hormone. Moreover, the extracts did not inhibit self-analgesia induced by restraint stress in mice and did not improve the performance of aged rats in the T-maze test (p>0.05). CONCLUSION: The tests employed in this study did not show evidence of adaptogenic activity in the three extracts of Heteropterys tomentosa.

Evaluation of antiulcer activity and mechanism of action of methanol stem bark extract of Lafoensia pacari A. St.-Hil. (Lytraceae) in experimental animals.

ETHNOPHARMACOLOGICAL RELEVANCE: Lafoensia pacari St.-Hil. is a tree native to the Brazilian Cerrado. Its bark macerate is popularly used in Brazilian folk medicine for the treatment of peptic ulcer, wound healing and inflammation. AIM OF THE STUDY: To evaluate the antiulcer activities of the methanol extract of Lafoensia pacari (MELP) and possible mechanisms of actions involved. MATERIALS AND METHODS: The stem bark of Lafoensia pacari was macerated in methanol to obtain the crude methanol extract of Lafoensia pacari (MELP). The gastroprotective and ulcer healing of MELP were evaluated using ethanol, indomethacin, cold-restraint stress-induced (acute) and acetic acid (chronic) ulcer models. The probable mode of action of MELP was also evaluated by determining intestinal transit, involvement of non-protein sulfhyhydryls (NP-SH), gastric mucus secretion, gastric secretory parameters and pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-17 (IL-17). Phytochemical analysis was carried out using classical methods and ellagic acid, one of the most important pharmacological active compounds was confirmed by HPLC. RESULTS: The results of the pharmacological studies on MELP demonstrated potent and effective gastroprotection against ethanol, indomethacin and cold stress-induced acute ulcers and ulcer healing in acetic acid induced chronic ulcer. MELP had no significant effect on the intestinal motility and it is also independent of mucus production but rather have a mucolytic effect. In pylorus-ligated rats the extract showed anti-secretory activity by decreasing total gastric juice volume and gastric acidity while increasing the gastric pH. The gastroprotection against ethanol is partially attributed to effective attenuation in the decrease in NP-SH levels, inhibition of the increases in the pro-inflammatory cytokines, TNF-α and IL-17. Phytochemical analysis of MELP revealed the presence of pyrrogalic tannins, saponins, steroids, triterpenoids and simple phenols, with ellagic acid being the major components. CONCLUSION: The results of this study showed that MELP possesses preventive and curative effects against gastric ulcer in experimental animals. These effects are partly dependent on its anti-oxidant, anti-secretory properties and inhibition of pro-inflammatory cytokines and independent of gastric/intestinal motility and mucus secretion. Ellagic acid, a compound of proven antiulcer activity, was found in MELP as the major component. These results confirmed the traditional use of MELP in Brazilian popular medicine for the treatment of gastric ulcers and shed some light on some of its mechanisms of action.

[Effect of transcranial electrostimulation on clinical and laboratory characteristics in patients with gastric ulcer].

The study included 100 patients with gastric ulcer aged from 16 to 60 years. In 58 patients, traditional treatment was supplemented by transcranial electrotherapy using a TRANSAIR-02 apparatus. Laboratory studies included measurements of lactoferrin (LF) and tumour necrosis factor-alpha (TNF-alpha), besides standard analyses. Combined treatment (traditional therapy plus electrostimulation) resulted in a significant reduction in duration of the main symptoms of the gastric ulcer depending on the severity of ulceration process, patients' age and sex. Moreover, it facilitated ulcer scarring and had beneficial effect on dynamics of serum LF and TNF-alpha levels.