Gastric Ulcer Area Research Articles

Covering Post-Endoscopic Submucosal Dissection Ulcers in Miniature Swine with Hexanoyl (Hx:C6) Group-Modified Alkaline-Treated Gelatin Porous Film (HAG) Induces Proper Healing by Decreasing Inflammation and Fibrosis

Background and Aims: Hexanoyl (Hx:C6) group-modified alkaline-treated gelatin porous film (HAG) is a newly developed degradable hydrogel characterized by strong adhesiveness and high affinity for vascular endothelial growth factor (VEGF). The aim of this study was to clarify the effect of HAG sheets on the healing process of post-endoscopic submucosal dissection (ESD) porcine gastric artificial ulcers. Methods: (1) To evaluate the adhesiveness of HAG sheets over time, we performed ESD to create 1 artificial ulcer and covered the lesion with 1 HAG sheet using 1 miniature swine. We observed 2 ulcers by endoscopic and microscopic examinations. (2) To examine the effect of HAG sheets on post-ESD ulcer healing, we performed ESD using 5 miniature swine. The artificial ulcers were covered with HAG sheets, or left uncovered after ESD (day 0), followed by macroscopic and microscopic examinations. On days 7 and 14, we observed 2 ulcers by endoscopic examinations. On day 14, the animals were sacrificed, and histological examination was performed on the 3 stomachs that could be extirpated. Results: (1) On day 7, adhesion of HAG sheets was observed. (2) Gastric ulcer area on day 7 was significantly larger in the covered ulcers than in the non-covered ulcers (p = 0.046). On day 14, although there was no significant difference in ulcer area irrespective of covering (p = 0.357), the covered ulcers tended to repair less fold convergence than non-covered ulcers. The covered ulcer sheets significantly decreased inflammatory cell infiltration (p = 0.011), but significantly increased the abundance of macrophages (p = 0.033), in submucosal layers. Also, the abundance of alpha-smooth muscle actin-positive cells in submucosal layers of the covered ulcers was significantly reduced (p = 0.044), leading to a decrease in collagen accumulation. In addition, fibrosis and atrophy of the muscularis propria were significantly lower for covered ulcers than for non-covered ulcers. Furthermore, microvessels and VEGF-positive cells were significantly more abundant in the submucosal layers of the covered ulcers (p < 0.001 and p = 0.024, respectively). Conclusions: HAG sheets induced post-ESD ulcer healing with less submucosal inflammation and muscularis propria injury and have the potential to decrease excess scarring.

Comparative Study of Najia and Nazi Acupunctures to Reduce Rat Gastric Ulcer

Gastric ulcer is a common digestive system disease, which leads to the serious decline in the life quality and effective therapies are in urgent need. Midnightmidday ebb flow acupunctures including Najia and Nazi acupunctures have been applied in clinics in China for more than one thousand years and the acupoints are selected according to the time rhythm. Najia acupuncture, namely day-prescription of acupoints, divides ten days (one cycle) into 120 two-hour periods and each period is coordinated with a meridian. Meanwhile, Nazi acupuncture, namely hour-prescription of acupoints, divides a day(one cycle) into 12 two-hour periods and each period is coordinated with a meridian. When there is a disease in a certain meridian, the relevant acupoints are operated in the corresponding time. However, the comparative efficacies of Najia and Nazi acupunctures on promoting the healing of gastric ulcer are still unknown. In this study, gastric ulcer rats were induced by acetic acid and were randomly divided into four groups: non-acupuncture group, normal acupuncture group, Najia acupuncture group and Nazi acupuncture group. After different treatments for continuous 10 days, the gained weight, gastric ulcer area and the thickness of gastric mucosa were measured and analyzed. Decreased ulcer area, increased mucosa thickness and dense scar tissue occurred in the Najia group and Nazi group compared to that in the non-acupuncture group (P&lt;0.05). However, there were no significant differences between Najia and Nazi acupuncture groups (P&gt;0.05). Thickness of gastric mucosa in Nazi acupuncture group increased significantly compared to normal acupuncture group (P&lt;0.05). Therefore, the findings in this study indicated that Najia and Nazi acupunctures had gastroprotective effects and accelerated the healing of acetic acid-induced gastric ulcer in rats, but no significant differences between them. It may provide valuable information for development of acupuncture for the treatment of gastric ulcer in clinics.

Evaluation of therapeutic potentials of α-Lipoic acid versus stem cells-derived microvesicles against experimentally–induced gastric ulcer in adult Male Albino Rats (Light and Electron microscopic study)

Background: Alpha-Lipoic acid (ALA), is an antioxidant endogenous substance. It is available in small amounts in food. Mesenchymal stem cells (MSCs) derived microvesicles (MSC-MVs) have numerous paracrine protective effects against tissue injury that are mediated by inflammatory, apoptotic and oxidative stress. Aim of the Work: Our study was done to assess the protective effects of Alpha Lipoic Acid versus MSC-MVs on indomethacin-induced gastric ulcer in rats. Material and Methods: Forty adult male rats were divided into: Group I (10 rats) represented control animals, and Group II (30 rats) involved ulcerated rats. The ulcerated group received a single gavage of indomethacin (30mg/kg B.Wt.) and was equally subdivided into: Subgroup ΙΙ-a (ulcerated subgroup), subgroup ΙΙ-b ulcerated rats that received a single intravenous dose of MSCs-MVs (0.5 mg/mL) and subgroup ΙΙ-c ulcerated rats that received ALA (100 mg/kg) orally for 3 days before ulcer induction. Antioxidant enzymes and ulcer index were assessed. Gastric tissue was examined by light and transmission electron microscopes.Results: Indomethacin caused marked damage of the gastric mucosa and ulcer index was significantly higher as compared to the control group. There was loss of the normal histological architecture and inflammatory cells infiltration. Ultrastructure sections revealed increased mucin granules in surface mucous secreting cells. Parietal cells showed dilatation of intracellular canaliculi. In ALA and in MSCs-MVs treated rat groups, there was a significant increase in antioxidant enzyme activities. The structure of the mucosa was significantly improved with a significant decrease in gastric ulcer area. Erosions, necrosis and inflammatory cell infiltration were significantly decreased. No major damage of endothelial cells was observed. The parietal cells count and the VEGF -positive cells were significantly decreased as compared with the control group. Conclusion: MSCs-MVs have significant superior therapeutic effects on gastric mucosa against indomethacin-induced gastric ulcer than the protective effects of α-Lipoic acid (ALA).

Safranal, a constituent of saffron, exerts gastro-protective effects against indomethacin-induced gastric ulcer

AimsSeveral natural products have been evaluated for management of gastric ulcer induced by non-steroidal anti-inflammatory drugs. Safranal, a plant-derived chemical, has a potent antioxidant and anti-inflammatory properties. The present study was aimed to evaluate possible gastro-protective effects of safranal against indomethacin-induced gastric ulcer in rats. Lansoprazole (a proton pump inhibitor) was used as a reference drug. Materials and methodsThirty rats were divided into five groups. Groups 1 and 2 received vehicle. Groups 3, 4 and 5 treated with 0.063, 0.25 and 1 mg/kg safranal. Group 6 received 30 mg/kg lansoprazole. All groups except of group 1 received indomethacin (50 mg/kg) ingestion. Six hours later, animals were euthanized and their stomachs were removed. Gastric contents volume and pH were measured. Gastric ulcer area and protective index were evaluated using image J software. Histological changes were evaluated by light microscope. Malondialdehyde (MDA) level, superoxide dismutase (SOD) activity, total antioxidant capacity (TAC) content, tumor necrosis factor-alpha (TNF-α) and Caspase-3 levels were determined in the gastric tissue. Key findingsSafranal and lansoprazole normalized gastric volume and pH, reduced gastric ulcer area and produced gastric protection. Indomethacin-induced histological changes and tissue biochemical alterations were ameliorated by the above-mentioned treatments. SignificanceThe results of the present study suggest the involvement of anti-secretory, anti-oxidant, anti-inflammatory and anti-apoptotic mechanisms in gastro-protective effect of safranal. In addition, gastro-protective effect of safranal was comparable to lansoprazole.

Gastro-protective effect of Biebersteinia multifida root hydro-methanolic extract in rats with ethanol-induced peptic ulcer.

Biebersteinia multifida is one of the native plants of Iran and its root is used in folk medicine. This study aimed to evaluate the gastro-protective effect of the hydro-methanolic extract of this plant's roots against ethanol-induced gastric ulcer in rats. The following five groups of seven rats were included in this study: control (C), gastric ulcer (GU), control omeprazole (CO) and two treatment groups (the latter 3 groups were rats with gastric ulcer that orally received omeprazole, 20 mg/kg, or the root extract at 150 and 300 mg/kg (BM 150 and BM 300, respectively) 1 hour before ulcer induction). One hour after ulcer induction, blood sampling was performed and after sacrificing animals, the stomachs were immediately removed. Gastric mucosal injury was studied grossly to determine the number and area of gastric ulcers. The level of nitric oxide (NO) and total antioxidant capacity (TAC) in gastric mucosa as well as serum TNF-α were determined. In GU group, severe mucosal injuries were observed (p<0.0001 as compared to C group). The lesions in CO and treatment groups were much milder than GU group by regarding ulcer area and number (p<0.001 for all cases). In treated (BM 150 and BM 300) groups, the gastric mucosal TAC and NO level were significantly higher than GU group (p<0.05 for all cases). Serum TNF-α level was not significantly different between GU and other groups. B. multifida possesses gastro-protective effects against ethanol-induced ulcer model; this effect is at least partly related to plant's antioxidant and NO production accelerating properties.

Protective effect of silkworm pupa oil on hydrochloric acid/ethanol-induced gastric ulcers.

Silkworm pupae are a traditional Chinese food, rich in various saturated and unsaturated fatty acids. Unsaturated fatty acids have a certain protective effect against oxidative damage. The present study used an animal model to determine the protective effect of silkworm pupa oil on hydrochloric acid / ethanol-induced gastric ulcer. Silkworm pupa oil is rich in unsaturated fatty acids, including palmitoleic acid 63.4 g kg-1 , oleic acid 249.1 g kg-1 , linoleic acid 47.0 g kg-1 , and linolenic acid 337.8 g kg-1 , whereas its unsaturated fatty acid content is 700 g kg-1 . Compared to a gastric ulcer control group, high and low doses of pupa oil reduced gastric ulcer area and gastric secretion, whereas gastric pH increased. It also increased serum antioxidant superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) levels, somatostatin (SST), and vasoactive intestinal peptide (VIP) levels, and reduced serum interleukin-6 (IL-6), interleukin-12 (IL-12), tumor necrosis factor (TNF-α), and interferon-γ (IFN-γ), motilin (MTL), and gastrin (GT) levels. RT-qPCR and western blot analyses indicated that silkworm pupa oil significantly increased CAT, GSH-Px, epidermal growth factor (EGF), Epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), Cu/Zn-SOD, Mn-SOD, and NF-kappa-B inhibitor-α (IκB-α) expression and lowered nuclear factor-kappa B (NF-κB), B-cell lymphoma-2 (Bcl-2), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) expression. Silkworm pupa oil treatment reduced oxidative damage and inflammation in mice, and high-dose silkworm pupa oil was superior to low-dose silkworm pupa oil, following ranitidine. © 2018 Society of Chemical Industry.

Gastroprotective effects of Kangfuxin against water-immersion and restraint stress-induced gastric ulcer in rats: roles of antioxidation, anti-inflammation, and pro-survival

Context: Kangfuxin (KFX) is widely used for the treatment of gastric and duodenal ulcer; however, more research is needed to determine the protective mechanisms of KFX in ameliorating gastric ulcer.Objective: To investigate the efficacy and potential mechanism of Kangfuxin liquid (KFX) in water-immersion and restraint stress (WIRS)-induced gastric ulcer.Materials and methods: Seventy rats were randomly divided into seven groups (n = 10) as follows: the control group (normal saline, i.g.), the model group (normal saline, i.g.), the KFX groups (2.5, 5 and 10 mL/kg, i.g.), the omeprazole group (20 mg/kg, i.p.) and Sanjiuweitai Granules group (1850 mg/kg, i.g.). The WIRS model was applied to induce stress ulcers after 7 days of drug administration. Afterwards, rats were sacrificed at 10 h induced by WIRS.Results: Pre-treatment with KFX (5,10 mL/kg) could effectively reduce the area of gastric ulcers and improve the pathological changes of ulcerated tissue. Moreover, KFX (5,10 mL/kg) increased the prostaglandin E2 (52%) and cyclooxygenase-1 (30%) levels, and improved malondialdehyde (54%), superoxide dismutase (58%), catalase (39%), and nitric oxide (11%) and TNF-α (9%), IL-6 (11%), MMP-9 (54%) and MMP-2 (53%) of ulcer tissue. Furthermore, pre-treatment with KFX dramatically increased IGF-1, PTEN, and Akt protein expression.Conclusions: Our results suggest that KFX has protective effects on WIRS-induced gastric ulcer via inflammatory reactions, oxidative stress inhibition, and pro-survival action, which were the results of activating the IGF-1/PTEN/Akt signalling pathway. Our results provide evidence of KFX for treating gastric ulcer.

Gastroprotective effect of limonene in rats: Influence on oxidative stress, inflammation and gene expression

BackgroundIn an increasing search for natural products that may heal the ulcers and avoid its recurrence, limonene appears as a promising candidate. Hypothesis/PurposeThe present study aimed to investigate the protective effect of limonene in ethanol-induced gastric ulcers, in addition, to investigate the involvement of antioxidant and anti-inflammatory activities, besides the modulation of gene expression. Study DesignMale Wistar rats were orally treated with vehicle (8% tween 80), carbenoxolone (100 mg/kg) or limonene (25, 50 or 100 mg/kg) and then orally received ethanol to induce gastric ulcers formation. MethodsThe activity of myeloperoxidase (MPO) was measured. Levels of glutathione (GSH) and activities of glutathione peroxidase (GPx), glutathione reductase (GR) and superoxide dismutase (SOD) were measured. We investigated the anti-inflammatory effect of limonene measuring the levels of pro-inflammatory cytokines tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), interleukin-1β (IL-1β) and anti-inflammatory cytokine interleukin-10 (IL-10) by ELISA. Additionally, we investigate through real-time PCR (qPCR) the gene expression of nuclear factor-kappa B (Nf-κb), Gpx, Il-1β, Mpo, and Il-10. ResultsOur results showed that limonene 50 mg/kg was the lowest effective dose, offering 93% of reduction in gastric ulcer area compared with the vehicle. There was an increase in mucus production and higher preservation of gastric mucosa integrity after treatment with limonene.There was a reduction in the MPO activity, a biomarker of neutrophils infiltration, and an increase in GPx activity, suggesting an antioxidant effect. Limonene displayed anti-inflammatory activity through decreasing the levels of TNF-a, IL-6, and IL-1β and increasing the level of IL-10. Limonene could down-regulate the expression of Nf-κb, Il-1β, and Mpo and up-regulate the expression of Gpx. ConclusionOur results demonstrate that oral treatment with limonene exerts gastroprotection through local mucosal defense mechanisms, such as increasing the mucus production, modulation of the oxidative stress and inflammatory response and inhibition of Nf-κb expression.

Gastroprotective and anti-ulcer effects of oxymatrine against several gastric ulcer models in rats: Possible roles of antioxidant, antiinflammatory, and prosurvival mechanisms.

Oxymatrine (OXY) has antioxidative and antiinflammatory activities. In the present work, we investigate the effects of OXY on gastric ulcer models and elucidate the underlying mechanisms of action. Ethanol, indometacin, and restraint water immersion stress-induced ulcerated models were used. The ulcer area was measured, and samples of gastric tissue were taken for pathological, histochemical, and biochemical analyses. OXY effectively reduced the area of gastric ulcers and improved the pathological changes of ulcerated tissue. OXY enhanced expression of Bcl-2, reduced Bax protein expression, and inhibited alcohol-induced apoptotic death in both ulcerated tissue and human gastric epithelial cells. OXY increased the prostaglandin E2 level and improved oxidative stress (malondialdehyde, superoxide dismutase, catalase, and nitric oxide) and inflammatory parameters (TNF-a, IL-6, and IL-1) of ulcer tissue. OXY prevented an inflammatory response via decreasing expression of p38, p-ERK, p-JNK, and inhibiting NF-κB p65 translocation from the cytoplasm to the nucleus. Our results reveal that OXY has remarkable protective effects on gastric ulcers. The action of OXY may be mediated via suppression of gastric inflammatory reactions, oxidative stress, and pro-apoptotic actions, which were the results of blockades of MAPKs and NF-κB signaling pathways. Our results provide evidence for the beneficial effects of OXY for treating peptic ulcers.

Prophylactic efficacy of patchoulene epoxide against ethanol-induced gastric ulcer in rats: Influence on oxidative stress, inflammation and apoptosis

Patchoulene epoxide (PAO), a tricyclic sesquiterpene isolated from the long-stored patchouli oil, has been demonstrated the anti-inflammatory activity in vivo based on our previous study. However, the gastric protective effect of PAO still remains unknown. Therefore, in the present study, ethanol-induced gastric ulcer model was carried out to evaluate the anti-ulcerogenic activity of PAO and to elucidate the potential mechanisms that involves. According to our results, macroscopic examination revealed that PAO could significantly reduce ethanol-induced gastric ulcer areas as compared with the vehicle group, which was also supported by the histological evaluation result. As for its potential mechanism, the anti-inflammatory activity of PAO contributed to gastric protection through reversing the imbalance between pro- and anti-inflammatory cytokines and modulating the expressions of NF-κB pathway-related proteins including p-IκBα, IκBα, p-p65 and p65. Besides, PAO was able to enhance the expressions of antioxidant enzymes including glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT), and down-regulate malonaldehyde (MDA), an indicator of lipid peroxidation. Furthermore, immunohistochemistry analysis exhibited potent anti-apoptosis effect of PAO, as evidence by down-regulating the protein expression of caspase-3, Fas and Fasl. Additionally, we also demonstrated that PAO could replenish PGE2 and NO mucosal defense. In conclusion, these findings suggested that PAO has gastric protective activity against ethanol and this might be related to its influence on inflammatory response, oxidative stress, apoptosis cascade and gastric mucosal defense.

Exendin-4, a glucagon-like peptide-1 analogue accelerates healing of chronic gastric ulcer in diabetic rats

BackgroundDiabetes mellitus is an independent risk factor for impaired healing of peptic ulcers, and there are currently no supplementary therapeutics other than the standard antipeptic medicine to improve the ulcer healing in diabetes. This study examined the potential pleiotropic effect of a glucagon-like peptide (Glp)-1 analogue exendin (Ex)-4 on the regeneration of gastric ulcer in streptozotocin-induced diabetic rats.Methods and resultsChronic ulcer was created in rat stomach by submucosal injection of acetic acid and peri-ulcer tissues were analyzed 7 days after operation. Ulcer wound healing was impaired in diabetic rats with suppressed tissue expression of eNOS and enhanced levels of pro-inflammatory reactions. Treatment with intraperitoneal injection of Ex4 (0.5 μg/kg/d) significantly reduced the area of gastric ulcer without changing blood glucose level. Ex-4 restored the expression of pro-angiogenic factors, and attenuated the generation of regional inflammation and superoxide anions. The improvement of ulcer healing was associated with increased expression of MMP-2 and formation of granulation tissue in the peri-ulcer area.ConclusionAdministration of Ex4 may induce pro-angiogenic, anti-inflammatory and anti-oxidative reactions in the peri-ulcer tissue of diabetic rats that eventually enhances tissue granulation and closure of ulcerative wounds. Our results support the potential clinical application of Glp-1 analogues as supplementary hypoglycemic agents in the antipeptic ulcer medication in diabetes.

Carbon monoxide released from its pharmacological donor, tricarbonyldichlororuthenium (II) dimer, accelerates the healing of pre-existing gastric ulcers.

Carbon monoxide (CO), a gaseous mediator produced by haem oxygenases (HOs), has been shown to prevent stress-, ethanol-, aspirin- and alendronate-induced gastric damage; however, its role in gastric ulcer healing has not been fully elucidated. We investigated whether CO released from tricarbonyldichlororuthenium (II) dimer (CORM-2) can affect gastric ulcer healing and determined the mechanisms involved in this healing action. Gastric ulcers were induced in Wistar rats by serosal application of acetic acid. Animals received 9days of treatment with RuCl3 [2.5mg·kg-1 intragastrically (i.g.)], haemin (5mg·kg-1 i.g.), CORM-2 (0.1-10mg·kg-1 i.g.) administered alone or with zinc protoporphyrin IX (ZnPP, 10mg·kg-1 i.g.), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 5mg·kg-1 i.g.), NG -nitro-l-arginine (l-NNA, 15mg·kg-1 i.g.), indomethacin (5mg·kg-1 i.g.) or glibenclamide (10mg·kg-1 i.g.). Gastric ulcer area and gastric blood flow (GBF) were assessed planimetrically, microscopically and by laser flowmeter respectively. Gastric mRNA/protein expressions of EGF, EGF receptors, VEGFA, HOs, nuclear factor (erythroid-derived 2)-like 2 (Nrf2), COX-2, hypoxia-inducible factor (HIF)-1α and pro-inflammatory iNOS, IL-1β and TNF-α were determined by real-time PCR or Western blots. CORM-2 and haemin but not RuCl3 or ZnPP decreased ulcer size while increasing GBF. These effects were reduced by ODQ, indomethacin, l-NNA and glibenclamide. CORM-2 significantly decreased the expression of pro-inflammatory markers, Nrf2/HO1 and HIF-1α, and up-regulated EGF. CO released from CORM-2 or endogenously produced by the HO1/Nrf2 pathway accelerates gastric ulcer healing via an increase in GBF, an up-regulation in EGF expression and down-regulation of the inflammatory response.

Transformation of patchouli alcohol to \u03b2-patchoulene by gastric juice: \u03b2-patchoulene is more effective in preventing ethanol-induced gastric injury

Pogostemonis Herba is a functional food approved in Asian countries. Its major constituent, patchouli alcohol (PA), possesses a gastroprotective effect and is reported to transform into β-patchoulene (β-PAE) under acidic conditions. To investigate whether β-PAE, the metabolite of PA, has a protective effect on the gastrointestinal tract, the formation of β-PAE by gastric juice and the anti-ulcerogenic potential of β-PAE against ethanol-induced gastric injury were evaluated. The Results indicated that PA was converted to β-PAE by rat gastric juice. Additionally, β-PAE was significantly better than PA at reducing the area of gastric ulcer. The overproduction of malondialdehyde, tumour necrosis factor-α, interleukin (IL)-1β, IL-6, Fas, FasL and caspase-3 was markedly inhibited by β-PAE while the underproduction of superoxide dismutase, glutathione and catalase was significantly improved. β-PAE also regulated the NF-κB and ERK1/2 signalling pathways. Our findings suggest that β-PAE has potential therapeutic efficacy for antiulcer treatment.

The Healing Effect of Probiotics on Indomethacin Induced Gastric Ulcer in Rats

Background : Probiotics are living organisms which upon ingestion in certain numbers exert health benefits beyond inherent basic nutrition, they are used for the treatment of Gastric ulcer. The lactobacillus rhamnosus, Bifidobacterium bifidum, Lactococcus lactis and Saccharomyces cerevisiae are the most significant groups of probiotic organisms. Objectives : The aim of this study is to investigate the effect of a probiotic strains for treatment of peptic ulcer. Methodology: Gastric ulcers were induced by indomethacin in rats .probiotics were given for three days. The strains significantly reduced gastric ulcer area as compared to control and negative control groups. Neutrophils were strongly increased for treatment of peptic ulcer. Results: The results showed that lactobacillus rhamnosus, Bifidobacteria, Lactococcus lactis and Saccharomyces cerevisiae that used in dairy milk products and yogurt enhanced gastric ulcer healing via stimulating immune system.

Gastroprotective Effect of Combination of Hot Water Extracts of Licorice (Glycyrrhiza glabra), Pulasari Stem Bark (Alyxia reinwardtii), and Sembung Leaf (Blumea balsamifera) Against Aspirin-Induced Gastric Ulcer Model Rats.

Licorice (Glycyrrhiza glabra), Pulasari stem bark (Alyxia reinwardtii) and Sembung leaf (Blumea balsamifera) are traditionally used to treat gastrointestinal disorders. The aim of the study was to investigate gastroprotective effect of hot water extracts combination of those herbal against aspirin-induced gastric ulcer model in rats. The combination consisted of fixed doses of Licorice 273 mg/kg BW and Sembung leaf 457.5 mg/kg BW, and also consisted of Pulasari stem in various doses i.e. 100 mg/kg BW (first group), 200 mg/kg BW (second and sixth group) and 300 mg/kg BW (third group). The fourth grup rats received sucralfate 360 mg/kg BW. Ten minute after seven consecutive days of drug administration, the rats were induced with aspirin 450 mg/kg BW except sixth group rats. The fifth group rats only received aspirin without any protective agents. The number and area of gastric ulcers were evaluated macroscopically. Whereas, histopatological observation was used for evaluation of mucosal damage score, and the number of eosinophils and mast cells. In the study, herbal extracts combination markedly exhibited protective effects indicated by less number and smaller area of gastric ulcers in comparison to those of aspirin group (P < 0.05). The score of mucosal damages were also decreased in herbal extracts combination groups. The number of eosinophils and mast cells of herbal combination groups were observed to be smaller than those of aspirin group (P < 0.05). In conclusion, herbal combination of Licorice (Glycyrrhiza glabra), Pulasari stem bark (Alyxia reinwardtii) and Sembung leaf (Blumea balsamifera) is potential to develop as a gastroprotective agent.

Benexate hydrochloride betadex modulates nitric oxide synthesis and cytokine expression in gastric ulcers.

The present study investigated benexate hydrochloride betadex (BHB)-mediated ulcer healing, and changes to microcirculation modulated through nitric oxide synthase (NOS) and anti-inflammatory activity. A rat model of gastric mucosal injury was established through injection of a 60% acetic acid solution into the stomach. Following ulcer induction, the rats were administered BHB orally for 5 days at doses of 0, 100, 300 or 1,000 mg/kg. The highest dose of BHB was also administered with or without L-NG-nitroarginine methyl ester (L-NAME). The area of gastric ulcers was determined by planimetry, and expression of cyclooxygenases (COX), cytokines and NOS in stomach tissues were measured using western blotting. Compared with the control group, gastric ulcer size was significantly decreased in the 1,000 mg/kg BHB-treated group (P<0.05). Administration of BHB led to a significant increase in endothelial (e)NOS expression (P<0.05). Although acetic acid co-treatment with L-NAME induced more severe mucosal damage, BHB decreased COX expression and tumor necrosis factor-α levels when administered with the nitric oxide inhibitor, L-NAME (P<0.05). BHB exhibited protective effects in a rat model of gastric ulcers, which were associated with a decrease in pro-inflammatory cytokine levels and the activation of eNOS.

The Protective Potential of Phyllanthus niruri and Corilagin on Gastric Lesions Induced in Rodents by Different Harmful Agents.

The gastroprotective effect of the methanol extract of Phyllantus niruri and its main constituent, corilagin, were studied in vivo. The extract (50, 125, or 250 mg/kg, p. o.) inhibited ethanol-induced lesions in rats by 43 % (p < 0.001), 69 % (p < 0.001), and 99 % (p < 0.001), respectively. It also inhibited the formation of indomethacin-induced gastric ulcers in rats by 80 % (p < 0.01), 89 % (p < 0.01), and 97 % (p < 0.01). A decrease in lipid hydroperoxide levels (p < 0.01) and in myeloperoxidase activity (p < 0.05) evidenced a reduction of oxidative damage and neutrophil infiltration in gastric tissues from ulcerated mice using ethanol/HCl. Potent in vitro free radical scavenger activity (IC50 = 0.07) using the DPPH assay was observed. In contrast, the extract (250 mg/kg, i. d.) did not show antisecretory activity in pylorus-ligated rats, and also failed to inhibit the H+,K+-ATPase activity in vitro. However, in pylorus-ligated rats, the extract (50, 125, and 250 mg/kg, i. d.) increased adhered mucus content by 22 % (p < 0.05), 28 % (p < 0.01), and 38 % (p < 0.01), respectively. The involvement of prostaglandins, nonprotein endogenous sulfhydryl compounds, α2-receptors, and endogenous nitric oxide in the gastroprotection elicited by the extract was also evaluated. Finally, corilagin reduced the lesion area of ethanol-induced gastric ulcers in mice by 88 % (30 mg/kg, p. o.; p < 0.001). Based on these results, it has been concluded that P. niruri methanol extract possesses gastroprotective activity by different and complementary pathways, which together promote an improvement in gastric cytoprotection. The presence of corilagin may partially explain the effectiveness of the extract against gastric damage.

Curcumin Blocks Naproxen-Induced Gastric Antral Ulcerations through Inhibition of Lipid Peroxidation and Activation of Enzymatic Scavengers in Rats.

Curcumin is a polyphenol derived from the plant Curcuma longa, which is used for the treatment of diseases associated with oxidative stress and inflammation. The present study was undertaken to determine the protective effect of curcumin against naproxen-induced gastric antral ulcerations in rats. Different doses (10, 50, and 100 mg/kg) of curcumin or vehicle (curcumin, 0 mg/kg) were pretreated for 3 days by oral gavage, and then gastric mucosal lesions were caused by 80 mg/kg naproxen applied for 3 days. Curcumin significantly inhibited the naproxen-induced gastric antral ulcer area and lipid peroxidation in a dose-dependent manner. In addition, curcumin markedly increased activities of radical scavenging enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase in a dose-dependent manner. Specifically, 100 mg/kg curcumin completely protected the gastric mucosa against the loss in the enzyme, resulting in a drastic increase of activities of radical scavenging enzymes up to more than the level of untreated normal rats. Histological examination obviously showed that curcumin prevents naproxen-induced gastric antral ulceration as a result of direct protection of the gastric mucosa. These results suggest that curcumin blocks naproxen-induced gastric antral ulcerations through prevention of lipid peroxidation and activation of radical scavenging enzymes, and it may offer a potential remedy of gastric antral ulcerations.

Protective effects of Weilikang decoction on gastric ulcers and possible mechanisms.

Although Weilikang decoction (WLK) has been used for gastric ulcer (GU) therapy in a clinical setting with good curative effect for >20years, the mechanism remains unclear. Several GU animal models, induced by ethanol, hydrochloric acid, aspirin, pylorus ligation, acetic acid and indomethacin, were used to investigate the gastroprotective effects of WLK decoction. Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), indomethacin, and N-ethylmaleimide (NEM) were pretreated, respectively, to investigate the action mechanism. Real-time polymerase chain reaction and Western blot analysis methods were used to determine the effects of WLK on indomethacin-induced GUs. The WLK-administered groups (2.5, 1.25 and 0.625g/kg) significantly reduced the GU areas induced by ethanol, hydrochloric acid and aspirin. Furthermore, the effects could be quenched by L-NAME and NEM, but not by indomethacin. The 2.5 and 1.25g/kg WLK groups showed significantly decreased effects on GU areas induced by pylorus ligation and acetic acid. WLK treatment significantly decreased mRNA expression on cyclooxygenase (COX)-1, COX-2, interleukin-6, tumor necrosis factor α and inducible nitric oxide synthase (iNOS) mRNA, but showed no effect on endothelial nitric oxide synthase mRNA expression. Western blot analysis result showed that WLK-treated groups markedly downregulated COX-2 protein expression. The anti-ulcer potential of WLK can be primarily attributed to its regulatory effects on nitric oxide, sulfhydryl compounds, and reduction effect on mucosal expression of proinflammatory cytokines.

Healing mechanisms of the hydroalcoholic extract and ethyl acetate fraction of green tea (Camellia sinensis (L.) Kuntze) on chronic gastric ulcers

Green tea is an infusion of unfermented leaves of Camellia sinensis (L.) Kuntze (Theaceae), traditionally used for the treatment of obesity, hypercholesterolemia, and gastric complaints. This study evaluated the mechanisms involved in the gastric ulcer healing of the hydroalcoholic extract from green tea (GEt), its ethyl acetate fraction, (GEAc) and epigallocatechin gallate (EGCG) using the model of acetic acid-induced gastric ulcer in rats. The chronic gastric ulcer was induced by application of 80 % acetic acid on serosal mucosa of rats. After 7 days of oral treatment with GEt and GEAc, the ulcer area, mucin content, inflammatory parameters (MPO and NAG), and antioxidant system (GSH and LOOH levels, SOD and GST activities) were evaluated. In vitro, the scavenging activity of GEt and GEAc were also measured. The antisecretory action was studied on the pylorus ligature method in rats. Oral treatment with GEt and GEAc reduced significantly the gastric ulcer area induced by acetic acid. The gastric ulcer healing was accompanied by increasing of mucin content, restoration of GSH levels and SOD activity, and reduction of MPO and LOOH levels. In addition, GEt and GEAc reduced the DPPH free radicals in vitro. Furthermore, the oral treatment of animals with GEt and GEAc did not alter the gastric acid secretion or cause signs of toxicity. Collectively, these results showed that GEt had a pronounced antiulcer effect, possibly through maintenance of mucin content and reduction of inflammation and oxidative stress. In addition, the compounds present in its ethyl acetate fraction could be responsible for the extract activity.