Ethanol-induced Gastric Ulcer Research Articles

Octreotide-based therapies effectively protect mice from acute and chronic gastritis

Gastritis is a common inflammation of stomach with multiple pathogenesis. This study was designed to investigate the protective effects of oral octreotide (OCT) against ethanol-induced acute gastric injury and H. pylori-induced chronic gastritis via promoting gastric mucosa restoration, reducing gastric acid secretion and inflammation. Male C57BL/6J mice were randomly divided and treated with three doses of OCT (0.5, 2.5, 10 mg/kg) alone or combined respectively with 10 mg/kg omeprazole (OME), 0.2 g/L metronidazole (MTZ)/0.1 g/L clarithromycin (CLR) in drinking water. Oxidative stress analysis, bacterial load analysis, qPCR, gastric histopathology examinations were performed in our study. Ethanol-induced acute gastric ulcer was restored by OCT alone at doses of 2.5 mg/kg, or combined with OME as indicated by markedly reducing Gastrin, Il-6 and Il1b expression through induction of Muc5ac and Occludin, significantly improving hyperacidity and gastric bleeding. As well, OCT combined with MTZ/CLR restored the integrity of gastric mucosa damaged by H. pylori via elevating the expression of Muc5ac and somatostatin receptor 2, decreasing inflammation and increasing the number of chorionic or glands. Besides, OCT is more suitable for long-term medication in the treatment of chronic gastritis than OME. In conclusion, our results proved that the newly developed oral OCT-based therapies were more effective to reverse gastric mucosa damage and inflammation in ethanol and H. pylori infection-induced gastric injury, it is of great significance for supplementing new clinical regimens for the treatment of acute and chronic gastritis.

Protective Effect and Potential Mechanism of the Traditional Chinese Medicine Shaoyao-Gancao Decoction on Ethanol-Induced Gastric Ulcers in Rats.

Background Shaoyao-Gancao decoction (SGD) is a classic prescription in traditional Chinese medicine. SGD is effective in the treatment of gastric and duodenal ulcers. However, the biological activity and possible mechanisms of SGD in the treatment of gastric ulcers have not been fully elucidated. The purpose of this study was to scientifically evaluate the protective effect and potential mechanism of SGD against ethanol-induced gastric ulcers in rats. Methods A single gavage of 10 mL/kg of 75% ethanol was used to establish a rat gastric ulcer model. A histopathological examination of the gastric tissue was performed. The levels of TNF-α, EGF, PGE2, SOD, and TBARS in gastric tissue were measured by ELISA. Cellular apoptosis in gastric tissues was assessed by TUNEL assay. The expression levels of caspase-3 and Bcl-2 were determined by immunohistochemistry. The potential mechanism of SGD in treating gastric ulcers was further studied using a network pharmacology research method. Results The gastric tissue of rats with ethanol-induced gastric ulcers had obvious injury throughout the mucosal layer, which was significantly weakened in rats treated with SGD. Furthermore, treatment with SGD significantly increased the levels of EGF, PGE2, SOD, and Bcl-2 and decreased the levels of TNF-α, TBARS, and caspase-3 in the gastric tissue of rats with ethanol-induced gastric ulcers. SGD reduced ethanol-induced cell apoptosis in gastric tissue from rats with gastric ulcers. A traditional Chinese medicine-based network pharmacology study revealed that SGD exerts its anti-gastric ulcer effect by acting on multiple pathways. Conclusions The above results indicate that SGD can improve gastric ulcers induced by ethanol. Moreover, this study demonstrated multicomponent, multitarget, and multipathway characteristics of SGD in the treatment of gastric ulcers and provided a foundation for further drug development research.

The ameliorative impacts of wheat germ oil against ethanol-induced gastric ulcers: involvement of anti-inflammatory, antiapoptotic, and antioxidant activities.

This study examined if wheat germ oil (WGO) has gastroprotective impacts against ethanol-induced gastric ulcer in rats. Rats were assigned into control, WGO, ethanol, omeprazole + ethanol, and WGO+ethanol. WGO prevented gastric ulceration and damage induced by ethanol, the same effect induced by omeprazole, a widely known medication used for gastric ulcer treatment. WGO reduced gastric ulcer index, nitric oxide, and malondialdehyde levels in the stomach. WGO boosted the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Bcl2, and the antioxidants. WGO showed inflammatory and anti-inflammatory impacts through the control of interleukin (IL)-1β, Tumor necrosis factor alpha (TNF-α), and IL-10 that were altered in ethanol-administered rats. Ethanol up-regulated caspase-3 and nuclear factor-kappa B (NF-kB) expression and showed histopathological changes such as necrosis and mucosal degeneration that were mitigated by pre-administration of WGO. Moreover, WGO decreased gastric immunoreactivity of NF-kB and increased transforming growth factor beta-1 (TGF-β1) that were associated with upregulation of Nrf2, heme oxygenase-1 (HO-1), and antioxidant expression and production. In conclusion, WGO reduced ethanol-induced stomach toxicity by regulating genes involved in oxidative stress, inflammation, and apoptotic/antiapoptotic pathways.

The ameliorative effects of cinnamon oil against ethanol-induced gastric ulcer in rats by regulating oxidative stress and promoting angiogenesis.

Cinnamonis one of the herbal resources belonging to the Lauraceae family, is commonly used in traditional medicine and as a flavoring agent. It has antioxidant and anti-inflammatory activities. Therefore, the present study was performed to evaluate the gastroprotective effect of cinnamon on ethanol-induced gastric ulcer in comparison to omeprazole. In Wistar rats, gastric ulcers were induced using one oral dose of 70% ethanol (5ml/kg b. w.) Cinnamon oil at doses of 2.5ml/kg body weight and omeprazole (a reference drug) at a dose of 20mg/kg body weight were orally administrated daily for 7days before ulcer induction. 1 h after ethanol administration blood samples were collected and then the stomachs of sacrificed rats were subjected to biochemical, macroscopic and histological, and immunohistochemical studies. Oral administration ofcinnamon oil significantly attenuated gastric ulcer as revealed by a significant increase in the gastric levels of enzymatic and non-enzymatic antioxidants namely CAT, SOD, GSH-Px, and GSH with a concomitant reduction in MDA level compared with those in the ethanol group. Pre-treatment ofcinnamon oil markedly improved the level of TNF-α and PGE content. Furthermore,cinnamon oilpre-treatment significantly increased the immunoreactivity of VEGF while decreasing the immunoreactivity of COX-II. These results were further supported by histopathological findings which revealed the curing effect ofcinnamon oilon the microscopic changes induced by ethanol toxicity. Cinnamon oil showed a potential gastroprotective effect on ethanol-induced gastric ulcer comparable to the gastroprotective effect of omeprazole, and its effect may be mediated through suppression of oxidative stress and gastric inflammation and promotion of angiogenesis.

Gastroprotective effect of hydroalcoholic extract from Agaricus blazei Murill against ethanol-induced gastric ulcer in mice

Ethnopharmacological relevanceThe use of mushrooms in medicine is quite old and the first report about the use of genus Agaricus in treatment of ulcers occurred in Byzantine period. This mushroom is widely consumed as food, tea, food supplements, as well as nutraceutical and cosmeceutical applications, being cultivated and appreciated in several countries such as Brazil, Korea, Japan and China. Aim of the studyThis study aimed to characterize the chemical profile and the potential gastroprotective effect of hydroalcoholic extract from Agaricus blazei Murill (HEAb). Materials and methodsThe extract was chemically characterized by elemental analysis, UPLC-QTOF-MSE, Nuclear Magnetic Resonance (NMR) and high-performance liquid chromatography (HPLC) techniques to elucidate the metabolites present in the extract. The quantification of phenolic compounds and the in vitro antioxidant activities were performed and the gastroprotective effect of this extract was evaluated against ethanol-induced gastric ulcer model. HEAb was administered by gavage at 5, 25 and 50 mg kg−1 and N-acetylcysteine at 300 mg kg−1 (positive control). Furthermore, the pathways of nitric oxide (NO), Cyclic Guanylate Monophosphate (cGMP), prostaglandins (PGs) and the involvement of ATP-sensitive K+ Channels were modulated. ResultsMannitol, malic acid, pyroglutamic acid, L-agaritine and L-valine were putatively identified by UPLC-QTOF-MSE in HEAb. In addition, it was possible to identify mannitol by the intense signals in the NMR spectra, being still quantified as the main compound in the extract by HPLC. The contents of total phenols and flavonoids corroborated with the good antioxidant activity of HEAb. This study observed that HEAb at 25 and 50 mg kg−1 had gastroprotection effect demonstrated by the reduction of histopathological parameters and the reduction of mastocytosis in the stomach of mice. ConclusionsIn this study was possible to conclude that HEAb has gastroprotective effect related to the involvement of NO and PG pathways in the ethanol-induced gastric ulcer model in mice.

Gastroprotective effects of water extract of domesticated Amauroderma rugosum against several gastric ulcer models in rats

Context Amauroderma rugosum (Blume & T. Nees) Torrend (Ganodermataceae) is an edible mushroom with medicinal properties. However, the effects of A. rugosum on gastric ulcer remain unclear. Objective To investigate the gastroprotective efficacy of water extract of A. rugosum (WEA) on gastric ulcer. Materials and methods Sprague-Dawley rats were randomly grouped as control, model, lansoprazole and 200, 100 and 50 mg/kg of WEA. After pre-treatment for seven days, ethanol- and indomethacin-induced gastric ulcer models were established. The gastric ulcer and histopathology were investigated. Enzyme-linked immunosorbent assay (ELISA), quantitative polymerase chain reaction (Q-PCR) and Western blot assays were conducted to explore the potential anti-inflammatory effect and mechanism of WEA. Additionally, the pyloric ligation model was used to explore the influence of WEA on gastric acid and mucus. Results Pre-treatment with WEA (200, 100 and 50 mg/kg) effectively reduced ulcerous area in both ethanol-induced (71%, 88% and 71%) and indomethacin-induced (77%, 65% and 86%) gastric ulcer model. The gastric levels of tumour necrosis factor-alpha (TNF-α) (34% and 50 mg/kg), interleukin-6 (IL-6) (32% and 100 mg/kg) and interleukin-1β (IL-1β) (36%, 45% and 41%) were reduced significantly (p < 0.05) by WEA. Serum nitric oxide was decreased significantly (p < 0.05) at 200 and 50 mg/kg and PGE2 concentration was increased remarkably (p < 0.05) at 100 mg/kg. Gene expression of inflammasome Nlrp3, and the nuclear translocation of nuclear factor-κB (NF-κB) P65 were significantly decreased by WEA pre-treatment. However, the pH of gastric acid and secretion of mucus did not show any significant change. Conclusions The gastroprotective effect of WEA on gastric damage is attributed to anti-inflammation through the inhibition on NF-κB P65 nuclear migration and Nlrp3 gene expression.

Gastroprotective effect of an active ingredients group of Lindera reflexa Hemsl. On Ethanol-Induced gastric ulcers in Rats: Involvement of VEGFR2/ERK and TLR-2/Myd88 signaling pathway

Lindera reflexa Hemsl. (LR) has been used for the treatment of gastrointestinal disorders. The present study was carried out to investigate the gastroprotective effect of an active ingredients group of Lindera reflexa Hemsl. (LRG) on ethanol-induced gastric ulcer in rats and its possible mechanisms. The ulcer area was measured, and samples of gastric tissue were taken for histochemical, pathological, and biochemical analyses. Pretreatment with LRG protected the gastric mucosa as seen by reduction the GUI and gastric juice volume, regulated gastric acid secretion. LRG counteracted the ethanol-induced oxidative stress by increasing the levels of depleted SOD and CAT as well as significantly attenuating the lipid peroxidation by reducing the levels of MDA and MPO. LRG also reduced release of inflammatory mediator TNF-α, increased the content of PGE2 and inhibited MTL secretion. Immunofluorescence and Western blot analyses confirmed that the co-localization of TLR-2 and MyD88 protein in the gastric mucosa of LRG-treated rats was significantly lower than that of rats with gastric ulcers. Furthermore, LRG also modulated the expression of Ki-67 antigens. LRG markedly increased the expression of phosphorylated form of extracellular signal-regulated kinaseVEGFR2, ERK1/2, AKT and p38, thereby protecting the gastric mucosa. These findings indicated that the gastroprotective effect of LRG is attributable to its antioxidant, anti-inflammatory, and antisecretory properties. In addition, LRG can ameliorate ethanol-induced gastric ulcers in rats by regulating the VEGFR2/ERK and TLR-2/MyD88 signaling pathways.

Relationship between Hormonal Modulation and Gastroprotective Activity of Malvidin and Cyanidin Chloride: In Vivo and In Silico Approach.

Peptic ulcers are lesions that affect the gastrointestinal tract and that can be triggered by external factors such as alcohol use. This study investigated the gastroprotective role of two anthocyanidins, malvidin and cyanidin chloride, in an ethanol-induced gastric ulcer model in male and female mice (ovariectomized and supplemented with 17β-estradiol or not) and aimed to evaluate the effectiveness of anthocyanidins in preventing the formation of lesions and to identify the underlying mechanisms, while considering hormonal differences. Moreover, in silico comparative analysis was performed to predict the properties and biological behaviors of the molecules. We observed that the hormonal status did not interfere with the gastroprotective action of malvidin, although antioxidant mechanisms were modulated differently depending on sex. On the other hand, cyanidin showed gastroprotective activity at different doses, demonstrating that, for the same experimental model, there is a need to adjust the effective dose depending on sex. In silico analysis showed that, despite being structurally similar, the interaction with receptors and target proteins in this study (myeloperoxidase, superoxide dismutase, catalase, and reduced glutathione) differed between the two molecules, which explains the difference observed in in vivo treatments.

Investigation on the Effects and Mechanisms of Alkaline Natural Mineral Water and Distilled Water on Ethanol-Induced Gastric Ulcers In Vivo and In Vitro

Studies have proven that alkaline water has a protective effect on gastric diseases. However, the underlying mechanism is not clear. Moreover, in some countries, especially in China, purified water (distilled water) is also an important form of drinking water, while its protective effect on gastric diseases is still unknown. This study aimed to compare the effects of distilled water (pH = 5.6 ± 0.3) and alkaline natural mineral water (pH = 9.3 ± 0.6) on ethanol-induced gastric ulcers in mice and to further clarify the underlying mechanisms. Pepsin activity, prostaglandin E-2 (PGE2) and heat shock protein 70 (HSP70), superoxide dismutase (SOD), reduced glutathione (GSH), and malondialdehyde (MDA), as well as the oxidative stress pathway related proteins such as nuclear factor erythroid-2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NADH quinone oxidoreductase 1 (NQO1) were measured. After alkaline natural mineral water treatment, the levels of PGE2 and HSP70 were significantly increased (p &lt; 0.05). Antioxidant indexes (SOD, GSH, and MDA) and Western blot results (Nrf2, HO-1, and NQO1) showed that alkaline natural mineral water did not alleviate gastric ulcers by improving oxidative stress. Pepsin activity assay displayed that the pepsin activity was significantly declined after alkaline natural mineral water treatment compared with the distilled water treatment (p &lt; 0.05). This study indicated that alkaline natural mineral water may alleviate the ethanol-induced gastric ulcers in mice by inhibiting the pepsin activity and increasing the levels of PGE2 and HSP70.

Ginkgolide protects against ethanol-induced gastric ulcer in rats through NLRP3 related pathway

Ginkgolide protects against ethanol-induced gastric ulcer in rats through NLRP3 related pathway

Antiulcer activity of proanthocyanidins is mediated via suppression of oxidative, inflammatory, and apoptotic machineries.

Gastric ulcer (GU) is a lesion in the gastric mucosa associated with excessive oxidative damage, inflammatory response, apoptotic events, and irritation which may develop into cancer. However, medications commonly used in GU treatment cannot normalize gastric mucosa, while causing several adverse effects. Proanthocyanidins (PAs) are dietary flavonoids with numerous biological and pharmacological activities. In the current investigation, we studied the potential anti-ulcerative activity of PAs against acidified ethanol (HCl/ethanol)-caused gastric ulceration. Fifty male albino Wistar rats were allocated into five equal groups: control, HCl/ethanol (3mL/kg), lansoprazole (LPZ, 30mg/kg)+HCl/ethanol, and PAs (100 and 250mg/kg)+HCl/ethanol. LPZ and PAs were applied one week before gastric ulcer induction. PAs pretreatment notably reduced gastric mucosal macroscopic and microscopic pathological changes in a dose-dependent manner. Additionally, PAs activated the innate antioxidant molecules including glutathione and its derived antioxidants (glutathione peroxidase and glutathione reductase), along with superoxide dismutase and catalase, while attenuating pro-oxidant formation, including malondialdehyde and nitric oxide. Interestingly, PAs supplementation at a higher dose suppressed gastric inflammatory and apoptotic responses, as demonstrated by the reduced levels of interleukin-1β, interleukin-6, tumor necrosis factor alpha, high-mobility group box 1, cyclooxygenase 2, prostaglandin E2, nuclear factor kappa-B, Bcl-2-associated X protein, and caspase-3, while B cell lymphoma 2 was elevated. Hence, PAs could exhibit antiulcer activity by protecting gastric tissue from the development of oxidative damage, inflammatory responses, and apoptosis events associated with ulceration. PRACTICAL IMPLICATIONS: Gastric ulcer is a lesion in the gastric mucosal layer associated with excessive inflammatory response, apoptotic events, oxidative damage, and irritation, and may develop into cancer with about 5%-10% morbidity rate. However, medications commonly used in GU treatment cannot normalize gastric mucosa, while causing several adverse effects. Therefore, new therapeutic approaches are needed to treat or prevent gastric ulceration. Proanthocyanidins (PAs, condensed tannins) are dietary flavonoids found in abundance in different plant species, including their fruits, bark, and seeds. Due to their potent antioxidative activity, PAs have been applied to prevent or treat oxidative stress-related diseases, including cancer, as well as metabolic, neurodegenerative, cardiovascular, and inflammatory disorders. Here, we examine the potential therapeutic role of proanthocyanidins (PAs) against acidified ethanol-induced gastric ulcer in rats through evaluating oxidative challenge, inflammatory response, apoptotic events, and histopathological changes in the gastric tissue.

Isolation, Characterisation and Evaluation of Antiulcerogenic Potentials of Probiotic Lactic Acid Bacteria Isolated from Fermented Milk and Palm Wine against Ethanol-Induced Gastric Ulcer in Mice

Background: Gastric ulcer is one of the most common gastrointestinal diseases with a worldwide prevalence of about 40% in the developed countries and 80% in Africa. Acid inhibitors, anticholinergics, histamine H2-antagonists and antibiotics are commonly used to treat gastric ulcer. However, the accumulating evidence for resistance to antibiotics and the side effects of antibiotics and acid inhibitors, anticholinergics and histamine H2-antagonists. Therefore, there is an urgent need for approaches to treat and prevent gastric ulcer. One alternative strategy is the use of probiotic lactic acid bacteria. Aim of the study: This study aimed to isolate and characterised probiotic lactic acid bacteria from palm wine and fermented milk, and to evaluate their antiulcerogenic potentials on ethanol-induced gastric ulcer in mice. Methods: Probiotic lactic acid bacteria were isolated from the fermented milk and palm wine using pour plate technique on MRS agar and identified using the 16S r RNA gene sequencing. For functional properties and selection, acid and bile salt tolerance were evaluated based on viable colony count on MRS agar. Two probiotic lactic acid bacteria were selected for in vivo studies. Fifty-four healthy young adult Balb/c mice were randomly divided into 9 groups of 6 mice each. Gastric ulcer was induced in mice using one oral dose of absolute ethanol (10 mL/kg body weight). The probiotic lactic acid bacteria (F1 and F2) at different doses (MF3 = 9 × 108 CFU/mL, MF6 = 1.8 × 109 CFU/mL and MF9 = 2.7 × 109 CFU/mL) and omeprazole (20 mg/kg) (a reference drug) were orally administrated daily for 14 days before ulcer induction. These mice were sacrificed 1hour after induction and the stomach contents were collected for volume and pH determination. The stomachs were subjected to macroscopic, biochemical and histopathological analysis. Results: Among the isolates obtained, two were considered to have the best acid and bile tolerance capacity (viable count > 7.5 logCFU/ml) and were identified as Limosilactobacillus fermentum strain BB101 (F1) and Lactobacillus casei strain 02 (F2). Oral administration of probiotics Lactic acid bacteria F1 and F2 significantly attenuated gastric ulcer as revealed by significant reduction (P lactobacillus fermentum strain BB101 and Lactobacillus casei 02 with excellent bile and acid tolerance capacity. Also, these probiotic lactic acid bacteria exhibit gastroprotective effect on ethanol-induced gastric ulcer via antioxidant, enhance gastric ulcer healing, antacids, and anti-secretary effects.

Protective Effect of Nigella sativa Seeds Extract against Ethanol-Induced Gastric Ulcer in Rats: Possible Soluble Epoxide Hydrolase Inhibition

Nigella sativa seeds methanolic extract was prepared by a simple maceration process. The extract was subjected to preliminary phytochemical screening and high-performance thin-layer chromatography for linoleic and linolenic acid and tested for in vitro soluble epoxide hydrolase inhibition activity. Then the extract (100, 150 and 200 mg/kg) was evaluated against ethanol-induced stomach ulcer in rats using 1-(1-propanoylpiperidin-4-yl)-3-(4-trifluoromethoxy)phenyl) urea (1 mg/kg) and omeprazole (20 mg/ kg) as reference standards. The plant extract contains flavonoids, alkaloids, proteins, free amino acids, tannins, flavonoids and linoleic acid. The in vitro soluble epoxide hydrolase inhibition test results reveal that Nigella sativa seeds methanolic extract inhibit human soluble epoxide hydrolase enzyme (half maximal inhibitory concentration=2.619 μg/ml). The Nigella sativa seeds methanolic extract reversed macroscopic and microscopic alteration and attenuated the levels of myeloperoxidase, tumour necrosis factor-alpha, interleukin-6, 5-hydroxyeicosatetraenoic acid in ulcer rats. These results were comparable with standard control. In conclusion, Nigella sativa seeds methanolic extract has a protective action against ethanolinduced ulcers in rats.

Gastroprotective Effects of Fraxin with Antioxidant Activity on the Ethanol-Induced Gastric Ulcer

Gastroprotective Effects of Fraxin with Antioxidant Activity on the Ethanol-Induced Gastric Ulcer

Pretreatment with water kefir reduces the development of acidified ethanol-induced gastric ulcers

To evaluate the gastroprotective and antioxidant effects of pretreatment with water kefir on ulcers induced with HCl/ethanol. All pretreatments lasted 14 days. Male mice were separated into five groups: the control (C) group received vehicle without ulcer induction; the ulcerated (U) group received vehicle; the lansoprazole (L) group received 30 mg/kg/day lansoprazole; the water kefir (WK15 and WK30) groups received WK at a dose of 0.15 or 0.30 ml/kg/day, respectively. Gastroprotection was measured by ulcer area, ulcer index and ulcer reduction percentage. Antioxidant effects were quantified by measuring advanced oxidized protein products (AOPPs), superoxide dismutase (SOD), and catalase activity in the stomach. Pretreatment with WK at both doses promoted gastroprotection against HCl/ethanol-induced ulcers much like the pretreatment with lansoprazole. In addition, WK decreased protein oxidation while increasing SOD and catalase activity. We concluded that pretreatment with water kefir increases the activity of antioxidant enzymes, preventing gastric lesions induced by HCl/ethanol by maintaining the antioxidant performance in gastric tissue.

Gastroprotective and Antioxidative Effects of the Traditional Thai Polyherbal Formula Phy-Blica-D against Ethanol-Induced Gastric Ulcers in Rats.

Phy-Blica-D is a traditional Thai polyherbal formula that has reduced oxidative stress in non-communicable diseases. However, evidence supporting the gastroprotective effects of Phy-Blica-D has not been previously reported. Therefore, this study aimed to evaluate the gastroprotective effects of Phy-Blica-D against gastric ulcers in rats and investigate the potential underlying mechanism. To estimate the possible mechanisms of action, we examined the levels of oxidative stress markers, such as reactive oxygen species (ROS) and malondialdehyde (MDA), as well as antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH). According to our results, rats treated with only 80% ethanol (vehicle group) exhibited significant increases in their ulcer area and ulcer index (UI). Moreover, the levels of ROS and MDA markedly increased in the vehicle group compared with the normal control group. Daily oral administration of Phy-Blica-D (500 and 1000 mg/kg) for 7 days not only significantly decreased the ulcer area and UI, but also remarkably decreased the ROS and MDA levels in gastric tissue. Gastric ulcers induced by ethanol had significantly decreased antioxidant enzyme activities (CAT and SOD) and non-enzymatic antioxidant (GSH), whereas pretreatment with Phy-Blica-D significantly improved the activities of CAT, SOD, and GSH. Moreover, after exposure to ethanol, the rats exhibited a significantly increased level of inducible nitric oxide synthase (iNOS), which was reduced after treatment with Phy-Blica-D. These findings suggest that Phy-Blica-D potentially exerts its gastroprotective effects by suppressing oxidative stress and stimulating antioxidant enzymes, which is one of the causes of destruction of cell membranes, and it is involved in the pathogenesis of acute gastric ulcers induced by ethanol.

Gastroprotective Effects of Periplaneta americana L. Extract Against Ethanol-Induced Gastric Ulcer in Mice by Suppressing Apoptosis-Related Pathways.

Although Periplaneta americana L. and its modern preparation, Kangfuxin liquid, have been extensively applied for ulcerative diseases in gastrointestinal tract (e.g., gastric ulcer (GU) and ulcerative colitis, the effective components and potential mechanisms) remain unclear. In accordance with the accumulating research evidences, the relieving/exacerbating of GU is noticeably correlated to focal tissue programmed cell death. Herein, gastro-protective effects of the effective Periplaneta americana L. extract (PAE) fraction were assessed in vitro and in vivo, involving in programmed cell death-related signaling channels. To screen the effective PAE fraction exerting gastroprotective effects, several PAE fractions were gained based on a wide range of ethanol solution concentration, and they were assessed on ethanol-induced ulcer mice. Based on HPLC investigation with the use of nucleosides, the chemical composition of screened effective PAE, extracted by 20% ethanol, was analyzed in terms of quality control. Based on CCK-8 assay, the protective effects on GES-1 cells, impaired by ethanol, of PAE were assessed. After 3 days pre-treatment with PAE (200, 400, 800 mg/kg), the gastric lesions were assessed by tissue morphology, and periodic acid-schiff (PAS) staining, as well as hematoxylin and eosin (H&E) based histopathology-related investigation. The levels for inflammation cytokines (IL1-β, TNF-α, IL-18, PGE2, and IL-6), antioxidant indices (SOD and MDA) were examined via ELISA. In the meantime, based on Western Blotting assay, the expression levels of some programmed cell death-related protein targets (NLRP3, caspase-1, NF-κB p65, MyD88, and TLR4) were analyzed. As revealed from the results, PAE is capable of alleviating gastric mucosa impairment, suppressing the inflammatory cytokines, and down-regulating the MyD88/NF-κB channels. Accordingly, 20% ethanol extract of Periplaneta americana L. would contribute its gastroprotective effects, thereby providing the evidence that its anti-GU mechanisms correlated with inhibiting programmed cell death channel.

EVALUATION OF GASTROPROTECTIVE POTENTIAL OF CAJANUS CAJAN SEEDS EXTRACT ON ETHANOL-INDUCED GASTRIC ULCER IN ALBINO RATS

Objective: The present study was undertaken to evaluate the gastroprotective potential of Cajanus cajan seed aqueous extract (CCSE) on experimentally induced gastric ulcer in albino rats. Methods: Preliminary acute toxicity study was conducted to determine the oral median lethal dose (LD50). Twenty (20) male rats divided into 5 groups (A-E) of 4 animals each were used. Group A (normal control) and B (ulcer model) received 10ml/kg distilled water. Groups C, D and E received Cimetidine (100mg/kg b.w intraperitoneally), 250mg/kg and 500mg/kg b.w of CCSE orally respectively, once daily for seven (7) days. On Day 8, gastric ulcers were induced in groups B – E using 80% ethanol (1ml/rat) prior to sacrifice. Ulcer indices were determined on excised stomach tissues prior to further processing for histological examination. Results: The LD50 of CCSE is greater than 5g/kg b.w. Cimetidine and CCSE treatments showed statistically significant decrease (p&lt;0.05) in ulcer indices compared to group B (ulcer model). Histological features revealed noticeable preservation of the gastric mucosa in consistence with the macroscopical findings. Conclusion: The present study revealed that C. cajan seed extract possesses gastroprotective properties against ethanol-induced gastric ulcers.

Tricholoma matsutake-Derived Peptides Show Gastroprotective Effects against Ethanol-Induced Acute Gastric Injury.

Acute gastric injury caused by ethanol is a frequent disorder of the gastrointestinal tract. In this study, we investigated the potential gastroprotective effects of Tricholoma matsutake-derived peptides against ethanol-triggered acute gastric injury and the associated mechanisms. Peptides SDLKHFPF and SDIKHFPF significantly attenuated the ethanol-induced decrease in GES-1 cell survival (82.39 ± 1.93 and 80.10 ± 1.08% vs 56.58 ± 1.86%), inhibited GES-1 cell apoptosis, and alleviated the ethanol-induced gastric mucosal injury (64.76 ± 3.98 and 49.29 ± 3.25%), ulcer index (3.33 ± 0.47 and 4.67 ± 0.47 vs 6.67 ± 0.47), and histopathological changes in mice. Peptide treatment inhibited the phosphorylation and nuclear translocation of nuclear factor kappa B (NF-κB), the secretion of tumor necrosis factor-α, interleukin-6, and endothelin-1. In addition, T. matsutake peptide pretreatment increased growth factor secretion, upregulated B-cell lymphoma-2, downregulated Bcl-2-associated X (Bax), and cleaved cysteinyl aspartate specific proteinase 3, thereby promoting gastric cell survival. These findings strongly suggest that T. matsutake peptides attenuate ethanol-induced inflammatory responses and apoptosis by suppressing NF-κB signaling activation, thereby enhancing gastric epithelial barrier functions.

Protective Effects of Chitosan-Bilirubin Nanoparticles Against Ethanol-Induced Gastric Ulcers.

PurposeGastric ulcers (GU) are a disease of the gastrointestinal tract that can be caused by excessive alcohol consumption and heavy use of nonsteroidal anti-inflammatory drugs. GU manifests predominantly as pathological damage, such as extensive inflammatory erosion and superficial bleeding of the gastric mucosa. Oxidative stress damage and the inflammatory response are now considered important predisposing factors for GU, suggesting that antioxidant and anti-inflammatory drugs could be treatments for GU. Nanoparticle drug carriers offer many advantages over conventional drugs, such as improved drug efficiency, increased drug stability, and increased half-life.MethodsWe designed chitosan-bilirubin conjugate (CS-BR) nanoparticles and assessed the anti-inflammatory and antioxidant abilities of CS-BR in gastric epithelial cells. Then, we evaluated the intragastric retention time and the anti-ulcer effects of CS-BR in vivo.ResultsThe in vitro data showed that CS-BR nanoparticles protect gastric epithelial cells against oxidative/inflammatory injury. The in vivo study demonstrated that CS-BR nanoparticles accumulate permanently in the stomach and exert powerful antioxidant and anti-inflammatory effects against GU.ConclusionThis study applied bilirubin to the treatment of GU and confirmed that CS-BR nanoparticles are effective at alleviating acute GU in an experimental model. The findings provide innovative ideas for prophylaxis against or treatment of GU.