Ethanol-induced Gastric Ulcer In Mice Research Articles

Protective effects of an alcoholic extract of Kaempferia galanga L. rhizome on ethanol-induced gastric ulcer in mice

Ethnopharmacological relevanceThe rhizome of Kaempferia galanga L., a medicinal and edible Plant, was widely distributed in many Asian and African counties. It has been traditionally used to treat gastroenteritis, hypertension, rheumatism and asthma. However, there is a lack of modern pharmacology studies regarding its anti-gastric ulcer activity. Aim of the studyThe objective of this study is to investigate the protective effects of an extract from K. galanga L. rhizome (Kge) and its active components kaempferol and luteolin on ethanol-induced gastric ulcer. Materials and methodsThe kge was prepared by ultrasonic-assisted extraction, and the contents of kaempferol and luteolin were determined by HPLC. The mice were randomly divided into seven groups: blank control (0.5 % CMC-Na; 0.1 mL/10 g), untreatment (0.5 % CMC-Na; 0.1 mL/10 g), Kge (100, 200 and 400 mg/kg), kaempferol (100 mg/kg) and luteolin (100 mg/kg) groups. The mice were treated intragastrically once daily for 7 days. At 1 h post the last administration, the mice in all groups except the blank control group were intragastrically administrated with anhydrous alcohol (0.1 mL/10 g) once to induce gastric ulcer. Then, fasting was continued for 1 h, followed by sample collection for evaluation by enzyme-linked immunosorbent assay and real-time reverse transcription polymerase chain reaction assay. ResultsThe contents of kaempferol and luteolin in Kge were determined as 3713 μg/g and 2510 μg/g, respectively. Alcohol induced severely damages with edema, inflammatory cell infiltration and bleeding, and the ulcer index was 17.63 %. After pre-treatment with Kge (100, 200 and 400 mg/kg), kaempferol and luteolin, the pathological lesions were obviously alleviated and ulcer indices were reduced to 13.42 %, 11.65 %, 6.54 %, 3.58 % and 3.85 %, respectively. In untreated group, the contents of Ca2+, myeloperoxidase, malondialdehyde, NO, cyclic adenosine monophosphate and histamine were significantly increased, while the contents of hexosamine, superoxide dismutase, glutathione peroxidase, and prostaglandin E2 were significantly decreased; the transcriptional levels of IL-1α, IL-1β, IL-6, calcitonin gene related peptide, substance P, M3 muscarinic acetylcholine receptor, histamine H2 receptor, cholecystokinin 2 receptor and H+/K+ ATPase were significantly increased when compared with the blank control group. After pre-treatment, all of these changes were alleviated, even returned to normal levels. Kge exhibited anti-gastric ulcer activity and the high dose of Kge (400 mg/kg) exhibited comparable activity to that of kaempferol and luteolin. ConclusionThe study showed that K. galanga L., kaempferol, and luteolin have protective effects against ethanol-induced gastric ulcers. This is achieved by regulating the mucosal barrier, oxidative stress, and gastric regulatory mediators, as well as inhibiting the TRPV1 signaling pathway and gastric acid secretion, ultimately reducing the gastric ulcer index.

Gastroprotective effects of polysaccharides from purple sweet potato (Ipomoea batatas (L.) Lam) on an ethanol-induced gastric ulcer via regulating immunity and activating the PI3K/Akt/Rheb/mTOR pathway.

The study aimed to investigate the alleviation of an ethanol-induced gastric ulcer in mice by apolysaccharide (PSP) from purple sweet potato (Ipomoea batatas (L.) Lam) and explore the mechanism. The anti-ulcer activity was determined by histopathological evaluation, total gastric acidity, pepsin activity, gastric ulcer index and gastric ulcer inhibition rate. The expression levels of inflammatory factors were detected using ELISA. A special protein meter was used to detect the content of immunoglobulin lgM, immunoglobulin lgG, and complements C3 and C4 in the serum of mice. The expression of CD4+/CD8+ lymphocyte subsets of mice was detected using flow cytometry. Western blot analysis was used to examine the effect of PSP on the PI3K/Akt/Rheb/mTOR pathway. The results showed that PSP could effectively reduce the total gastric acidity, pepsin activity, and the index and inhibition rate of gastric ulcers. At the same time, PSP could significantly increase the levels of immunoglobulins (lgG and lgM) and complements (C3 and C4). It could also increase the activity of peritoneal macrophages in mice and the expression of CD4+/CD8+ in the spleen. ELISA analysis showed that the contents of TNF-α, IL-1β and IL-6 were significantly decreased and the content of IL-10 was significantly increased in the PSP group. The western blot analysis showed that PSP could upregulate the relative protein expressions of MUC5AC, PI3K, p-Akt, Rheb and mTOR. These results indicate that PSP can activate the PI3K/Akt/Rheb/mTOR signaling pathway to improve the immunity of mice and maintain the balance of the immune system, thereby protecting the gastric mucosa and improving stress gastric ulcers.

The Antioxidant and anti-inflammatory Activity of Selenium and Lecithin Combination Against ethanol-induced Gastric Ulcer in mice via Modulating IGF-1/PTEN/Akt/FoxO3a Signaling.

Gastric ulcers are one of the most prevalent gastrointestinal disorders. The current study investigated the antioxidant and anti-inflammatory effects of selenium (Se) and lecithin (Lec) alone and in combination against ethanol-induced gastric ulcers in mice, and their ability to modulate insulin-like growth factor-1 (IGF-1)/ Phosphatase and tensin homologue deleted on chromosome 10 (PTEN)/ Protein kinase B (Akt)/ Forkhead box O3a (FoxO3a) signaling. The mice were divided into normal, ethanol, Se + ethanol, Lec + ethanol, Se + Lec + ethanol, and omeprazole + ethanol groups. Treatment with the selected doses was continued for 14 days before a single dose of absolute ethanol (5 ml/kg body weight) was administered to induce gastric ulcers in mice. The results showed that pretreatment with Se and Lec combination effectively decreased both the macro- and microscopic gastric lesions and increased the protection index compared to the ethanol group. Remarkably, the Se and Lec combination decreased the levels of reactive oxygen species, malondialdehyde, and cytochrome c and increased glutathione, glutathione peroxidase, and thioredoxin reductase activities in gastric tissues. The Se and Lec combination increased prostaglandin E2 and interleukin-10 levels but decreased tumor necrosis factor-α, interleukin-6 and interleukin-1β levels compared to either treatment alone. Interestingly, this combination decreased the expression of IGF-1, p-Akt, and FoxO3a proteins and increased PTEN expression in gastric tissues. The gastric tissues examination by hematoxylin and eosin staining confirmed these results. Therefore, the Se and Lec combination showed superior protective effects against ethanol-induced gastric ulcers in mice, compared to either treatment alone, through antioxidant, and anti-inflammatory activities, in addition to modulating IGF-1/PTEN/Akt/FoxO3a pathway signaling.

Gastroprotective effects of Machilus zuihoensis Hayata bark against acidic ethanol-induced gastric ulcer in mice.

In traditional medicine, Machilus zuihoensis Hayata bark (MZ) is used in combination with other medicines to treat gastric cancer, gastric ulcer (GU), and liver and cardiovascular diseases. This study aims to evaluate the gastroprotective effects and possible mechanism(s) of MZ powder against acidic ethanol (AE)-induced GU and its toxicity in mice. The gastroprotective effect of MZ powder was analyzed by orally administering MZ for 14 consecutive days before AE-inducing GU. Ulcer index (UI) and protection percentage were calculated, hematoxylin and eosin staining and periodic acid-Schiff staining were performed, and gastric mucus weights were measured. The antioxidative, anti-inflammatory, and anti-apoptotic mechanisms, and possible signaling pathway(s) were studied. Pretreatment with MZ (100 and 200mg/kg) significantly decreased 10μL/g AE-induced mucosal hemorrhage, edema, inflammation, and UI, resulted in protection percentages of 88.9% and 93.4%, respectively. MZ pretreatment reduced AE-induced oxidative stress by decreasing malondialdehyde level and restoring superoxide dismutase activity. MZ pretreatment demonstrated anti-inflammatory effects by reducing both serum and gastric tumor necrosis factor-α, interleukin (IL)-6, and IL-1β levels. Furthermore, MZ pretreatment exhibited anti-apoptotic effect by decreasing Bcl-2 associated X protein/B-cell lymphoma 2 ratio. The gastroprotective mechanisms of MZ involved inactivations of nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) and mitogen activated protein kinase (MAPK) signaling pathways. Otherwise, 200mg/kg MZ didn't induce liver or kidney toxicity. In conclusion, MZ protects AE-induced GU through mucus secreting, antioxidative, anti-inflammatory, and anti-apoptotic mechanisms, and inhibitions of NF-κB and MAPK signaling pathways.

UPLC-QTOF-MS/MS-based metabolomic approach and gastroprotective effect of two chemotypes of Egletes viscosa (L.) less. against ethanol-induced gastric ulcer in mice.

Egletes viscosa (L.) (macela) is a native wild herb that can be found in different states of northeastern Brazil. The infusions of its flower buds are traditionally used for the treatment of gastrointestinal disorders. E. viscosa possesses two chemotypes (named A and B), distinguishable by the composition of the essential oil from the flower buds. Although there are previous studies of the gastroprotective effect of the isolated constituents of E. viscosa, its infusions have not been investigated yet. The present study aimed to evaluate and compare the chemical composition and the gastroprotective effect of flower bud infusions of E. viscosa from chemotype A (EVCA) and chemotype B (EVCB). Sixteen infusions were brewed with flower buds according to the traditional preparation mode and were analyzed through a UPLC-QTOF-MS/MS based metabolomic approach for determination of their metabolic fingerprints and quantification of bioactive compounds. Afterward, these data were analyzed by chemometric methods (OPLS-DA) for discrimination of the two chemotypes. Additionally, infusions of EVCA and EVCB (50, 100 and 200mg/kg, p.o.) were evaluated on gastric ulcers induced by absolute ethanol (96%, 0.2mL, p.o.) in mice. To elucidate the gastroprotective mechanisms, the effect of EVCA and EVCB on gastric acid secretion and gastric wall mucus was determined and the role of TRPV1 channels, prostaglandins, nitric oxide and KATP channels were assessed. Moreover, the oxidative stress-related parameters and the histological aspects of the stomach tissue were analyzed. The chemotypes can be discriminated from each other using UPLC-QTOF-MS/MS chemical fingerprints. Both chemotypes presented similar chemical compositions, consisting basically of caffeic acid derivatives, flavonoids and diterpenes. The quantification of bioactive compounds demonstrated that chemotype A possesses more ternatin, tanabalin and centipedic than chemotype B. EVCA and EVCB (50, 100 and 200mg/kg, p.o.) significantly decreased the severity of ethanol-induced gastric lesions, as shown by a reduction in histological alterations and leucocyte infiltration in gastric tissue. The gastroprotective mechanism of both infusions involves an antioxidant effect, maintenance of gastric mucus and reduction gastric secretion. Stimulation of endogenous prostaglandins and nitric oxide release, activation of TRPV1 channels, and KATP channels are also involved in the gastroprotection of the infusions. The gastroprotective effect of EVCA and EVCB was equivalent and mediated through antioxidant and antisecretory actions, including the activation of TRPV1 receptors, stimulation of endogenous prostaglandins and nitric oxide, and opening of KATP channels. The presence of caffeic acid derivatives, flavonoids and diterpenes in both infusions is involved in mediating this protective effect. Our findings support the traditional use of infusions of E. viscosa for gastric disorders regardless of the chemotype.

Evaluation of gastroprotective effect of jujube honey in ethanol-induced stomach ulcer in mice

Honey has been widely documented to have therapeutic benefits, especially on the healing of wounds, digestive disorders, and as an antimicrobial agent. It’s known that stomach ulcers are one of the most prevalent diseases that affect humans with no effective treatment. The objective of this study was to investigate the gastroprotective effects of jujube honey against ethanol-induced gastric ulcer in mice and to explore possible mechanism of its action on the gastric mucosa. Stomach’s tissues were examined for ulcerative lesions and white blood cell count (WBC), plasma C-reactive protein (CRP) and nitric oxide (NO) for clinical inflammation evaluation. The antioxidant enzyme activities were investigated using the measurement of superoxide dismutase (SOD) and catalase. Treatment with jujube honey reduced the ulcer index and preserved gastric tissue. It also decreased the inflammatory response by reducing WBC and plasma levels of CRP and NO in ulcerative group. In addition, jujube honey-treated group showed increased antioxidant enzyme activities of catalase and SOD. Furthermore, diluted jujube honey is more effective in preserving mucosal gastric integrity. In conclusion, these findings suggest that jujube honey, especially with dilution, may exert a protective effect against ethanol-induced gastric ulcer, through the improvement of antioxidant system and suppression of the inflammatory response via its bioactive compounds.

Selective accumulation of ionic nanocrystal H2 storage system as an in situ H2/boric acid nanogenerator fights against ethanol-induced gastric ulcers

Ethanol is a potential causative factor of gastric ulcers, which are associated with gastric injury and the overproduction of reactive oxygen species. Molecular hydrogen (H2) is reportedly a benign antioxidant and boric acid is an effective medication in repairing deep wounds. In this work, a nanoparticle system that consists of potassium borohydride ionic nanocrystals (KBH4 NCs) with a high H2 storage capacity is developed for the treatment and prevention of ethanol-induced gastric ulcers in mice. H2-rich water (HRW) is used as a control. Since the evolution of gaseous H2 from the HRW is abrupt, most of the evolved H2 gas is lost to the surrounding environment before and during oral administration. By contrast, KBH4 NCs can be trapped at the defect sites of ulcerated regions, reacting with the gastric fluid to generate sustainably gaseous H2 and boric acid, mitigating oxidative stress and excessive inflammation in tissues and repairing the gastric injury. Additionally, the protection that is afforded by gastric mucosa against ethanol-induced damage is stronger in mice that have been pretreated with KBH4 NCs than in those that have been pretreated with HRW, indicating the protective effect of KBH4 NCs. Overall, the data suggest that the as-developed KBH4 NCs are a promising oral formulation for the effective management of gastric ulcers.

Untargeted serum and liver metabolomics analyses reveal the gastroprotective effect of polysaccharide from Evodiae fructus on ethanol-induced gastric ulcer in mice

This study aimed at investigating the gastroprotective effect of Evodiae fructus polysaccharide (EFP) against ethanol-induced gastric ulcer in mice. Biochemical indexes along with untargeted serum and liver metabolomics were determined. Results showed that pre-treatment of EFP alleviated ethanol-induced gastric ulcer in mice. EFP lessened oxidative stress and inflammation levels of stomachs, showing as increments of SOD and GSH-Px activities, GSH content and IL-10 level, and reductions of MDA and IL-6 levels. Meanwhile, EFP activated the Keap1/Nrf2/HO-1 signaling pathway through increasing Nrf2 and HO-1 protein expressions, and decreasing Keap1 protein expression. Serum and liver metabolomics analyses indicated that 10 metabolic potential biomarkers were identified among normal control, ulcer control and 200 mg/kg·bw of EFP groups, which were related to 5 enriched metabolic pathways including vitamin B6 metabolism, nicotinate and nicotinamide metabolism, pentose phosphate pathway, bile secretion and ascorbate and aldarate metabolism. Further pearson's correlation analysis indicated that there were some positive and negative correlations between the biomarkers and the biochemical indexes. It could be concluded that the gastroprotection of EFP might be related to anti-oxidative stress, anti-inflammation, activation of Keap1/Nrf2/HO-1 signaling pathway and alteration of metabolic pathways. This study supports the potential application of EFP in preventing ethanol-induced gastric ulcer.

Dimethyl Cardamonin from Fruits of Campomanesia reitziana D. Legrand Promotes Gastroprotection and Gastric Healing Effects in Rodents.

Campomanesia reitziana D. Legrand (Myrtaceae) displays antiulcer properties when given to rodents. The major active chemical components of C. reitziana are chalcones, including 4',6'-dihydroxy-2'-methoxy-3',5'-dimethylchalcone or dimethyl cardamonin (DMC); therefore, we hypothesized that this compound could have antiulcer effects and the present study aimed to evaluate its gastroprotective and gastric healing properties. DMC was isolated from the fruits of C. reitziana, and its gastroprotective effect was evaluated by ethanol and indomethacin-induced gastric ulcer models in mice (0.1 mg/kg, i.p. and 1 and 3 mg/kg, p.o.). Oxidative stress and inflammatory parameters were analyzed in the gastric tissue. Moreover, its gastric healing effect was evaluated in rats. In addition, the compound's mode of action was evaluated in vivo and in vitro by measuring H+ -K+ -ATPase activity. Finally, the cytotoxic potential of DMC was tested in fibroblasts and human gastric adenocarcinoma cells. The DMC reduced the ethanol-induced gastric ulcer in mice by 77 %, increased the adhered mucus, and reduced lipoperoxides levels. The block of nonprotein sulfhydryls (NP-SH) compounds by pretreatment with N-ethylmaleimide (NEM), the inhibition of nitric oxide synthase with Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), or the antagonism of α2 receptor using yohimbine reversed the gastroprotective effects of DMC. Furthermore, DMC reduced the acidity of gastric content in pylorus-ligated rats but did not change H+ , K+ -ATPase (isolated from rabbit) activity in vitro. DMC reduced the lesion area in acetic acid-induced ulcers and decreased myeloperoxidase activity. DMC did not change the viability of fibroblast cells (L929) but reduced the viability of human gastric adenocarcinoma cells (AGS). The results confirmed that DMC could significantly enhance the gastric healing process and prevent ulcers due to improving protective factors on the gastric mucosa and reducing gastric acid secretion.

Snail Mucus Protective Effect on Ethanol-Induced Gastric Ulcers in Mice.

Nowadays, an increased interest in natural compounds with preventive or therapeutic potential for various diseases has been observed. Given the involvement of oxidative stress in the pathogenesis of gastric ulcer (GU) and the wide range of bioactive compounds isolated from snails, this study aimed to investigate the protective effect of Cornu aspersum (Müller, 1774) mucus on ethanol-induced GUs. Male albino mice were divided into Control, Ethanol, Mucus + Ethanol and Mucus + Omeprazole treated groups. The GUs were induced by administration of 96% ethanol (10 mL/kg, per os). One hour before ulcer induction, the mice of Mucus + Ethanol group were pretreated with mucus (20 mg/kg, per os), and the mice of Mucus + Omeprazole group were pretreated with omeprazole (20 mg/kg, per os). Ethanol administration caused grave lesions of gastric mucosa and a significant decrease of glutathione (GSH) and superoxide dismutase (SOD), catalase, and glutathione reductase (GR) activities. In the animals with mucus or omeprazole pre-administration compared to the Ethanol group, the following were observed: only a small number of hemorrhagic fields, significantly reduced GU index with calculated 73% protection by mucus and 78% protection by omeprazole, and significant recovery of mucosal GSH and SOD and GR activities. In addition, the mucus inhibited Helicobacter pylori growth. Thus, the protective effect of C. aspersum mucus on both gastric mucosa and gastric antioxidant potential in ethanol-induced GU model suggests that it may serve as a good tool for prevention of this disease.

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.

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 < 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 < 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.

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.

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.

The Gastroprotective Effect of Naringenin against Ethanol-Induced Gastric Ulcers in Mice through Inhibiting Oxidative and Inflammatory Responses.

Naringenin is a major flavanone found in grapes, tangelos, blood oranges, lemons, pummelo, and tangerines. It is known to have anti-inflammatory, antioxidant, anticancer, antimutagenic, antifibrogenic, and antiatherogenic pharmacological properties. This study aims to investigate the anti-inflammatory effects of naringenin in ethanol-induced gastric damage in vivo and ethanol-stimulated KATO III cells in vitro. Our results showed that pretreatment with naringenin significantly protected mice from ethanol-induced hemorrhagic damage, epithelial cell loss, and edema with leucocytes. It reduced gastric ulcers (GU) by suppressing ethanol-induced nuclear factor-κB (NF-κB) activity and decreasing the levels of nitric oxide (NO), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and myeloperoxidase (MPO). In addition, pretreatment with naringenin might inhibit the secretion of TNF-α, IL-6, and IL-8, as well as the proteins cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) via the suppression of NF-κB and mitogen-activated protein kinase (MAPK) signaling in ethanol-stimulated stomach epithelial KATO III cells. Together, the results of this study highlight the gastroprotective effect of naringenin in GU of mice by inhibiting gastric secretion and acidity, reducing inflammation and oxidative stress, suppressing NF-κB activity, and restoring the histological architecture. These findings suggested that naringenin has therapeutic potential in the alleviation of ethanol-induced GU.

Effects of the diphenylheptane extract of Alpinia officinarum rhizomes on ethanol-induced gastric ulcers in mice.

Objective(s):Experimental studies have revealed that Alpinia officinarum Hance (Zingiberaceae) exhibits a gastrointestinal protective effect. The present study aimed to investigate the effects of diphenylheptanes (DPHs) extracted from A. officinarum rhizomes on ethanol-induced gastric ulcers in BALB/c mice.Materials and Methods:A total of 60 female BALB/c mice were divided into six groups as follows: negative control, which received sodium carboxymethyl cellulose; positive control, which received ethanol; treatment control, which received ethanol+ranitidine; ethanol+high dose of DPHs; ethanol+medium dose of DPHs; ethanol+low dose of DPHs. Different doses of DPHs were administered orally once daily for seven consecutive days before the animals were subjected to ethanol-induced gastric ulcers.Results:Various doses of DPHs significantly reduced Gastric ulcers index when compared with the positive control. DPHs treatments and treatment control increased the activity of superoxide dismutase; decreased the levels of inflammatory mediators, malondialdehyde, motilin, and gastrin; decreased the activity of inducible nitric oxide synthase and cyclooxygenase-2; and inhibited the expression of Toll-like receptor 4, myeloid differentiation factor 88, and nuclear factor-κB at the protein and mRNA levels. In addition, DPHs inhibited the expression of transient receptor potential vanilloid 1, calcitonin gene-related peptide, and increased the expression of substance P at the protein and mRNA levels. Conclusion:The protective effect of DPHs extracted from A. officinarum rhizomes against ethanol-induced gastric damages in mice suggests that the extract can be used as an auxiliary supplement for the prevention and treatment of gastric ulcers.

Pistacia atlantica Desf. roots extract: LC-ESI-MS Analysis, antioxidant activity and gastroprotective effect on experimentally-induced ultrastructural gastric ulcers in mice

ABSTRACT Pistacia atlantica Desf. (Atlas Pistachio) is an Anacardiaceae tree traditionally used in Tunisia for the treatment of ophthalmic, stomatitis, and digestive tract diseases. In the present study, the Pistacia atlantica Desf. roots extract (PR) was phytochemically analyzed, for the first time, by LC-ESI-MS for phenolic and flavonoid contents, in vitro tested for its potential antioxidant activity based on the 2.2-diphenyl-1-picrylhydrazyl (DPPH) and the reduced power essays (FRAP), and in vivo tested for its ability to shield against ethanol-induced gastric ulcer in mice. The LC-ESI-MS analysis proved the identification of 12 compounds, including Quinic, Gallic, and Protocatechuic, as major phenolic acids and high levels of flavonoids, such as Catechin, Epicatechin, and Cirsiliol. PR also exhibited a mild in vitro antioxidant activity when compared with ascorbic acid. In vivo pretreatment of ethanol-ulcerated mice with PR doses 50 mg/kg and 100 mg/kg body weight (b.w) significantly reduced (P< .05) gastric lesions at a rate of 20.10% and a rate of 40.90%, respectively, when compared with 60.70% rate of sucralfate (50 mg/kg b.w) evidenced by a dose-dependent manner increase in the gastric mucosa enzymatic (SOD, CAT, GPx) antioxidant levels, the decline of the lipid peroxidation, and the preservation of normal gastric superficial epithelium. The underlying mechanism of PR antiulcerogenic activity could be due to a synergistic effect of phenolic acids and flavonoid contents which enhances the gastric antioxidant defense system. Abbreviations: BHT: butylated hydroxytoluene, b.w: body weight, CAT: catalase, DPPH:1-Diphenyl-2-picrylhydrazyl, DW: dry weight, EtOH: ethanol, FRAP: Ferric reducing antioxidant power, GAE: gallic acid equivalents, GPx: Glutathione peroxidase, QE: quercetin equivalents, LC-ESI-MS: Liquid chromatography-Electrospray Ionization-Tandem Mass Spectrometry, MDA: malondialdehyde, PR: Pistacia root, TBA: thiobarbituric acid reagent, TBARS: thiobarbituric acid reactive substances, TCA: trichloroacetic acid, SOD: Superoxide dismutase.

Protective effect of snail\xa0secretion filtrate against ethanol-induced gastric ulcer in mice

Gastric ulcer or peptic ulcer is a common disease worldwide. Basically, it develops when there is an imbalance between the protective and aggressive factors, especially at the luminal surface of epithelial cells. Thus, there is a constant interest in research new drugs for treatment of gastric ulcer. The snail secretion is a dense mucous, that covers the external surface of the snails, with important functions for the survival of snails. The biological proprieties of snail Helix Aspersa Muller mucus it has been known for centuries to treat human disorders in particular for skin disease. Recently the use of snail mucus has seen a worldwide increase, as a component in cosmetic product and it has been used in particular for the management of wound and skin disorders. In this study we use a murine model of ethanol intragastric administration which has been widely used to test the drugs efficacies and to explore the underlying mechanism for gastric ulcer development. The intragastric ethanol administration causes several mucosal damages and an induction of a severe inflammatory response. Our results show a significant protective effect of snail secretion filtrate in reducing macroscopic and histological lesions, as well the protective effect on mucus content, oxidative stress and inflammatory response. In conclusion this study demonstrate the protective effect of intragastrical snail secretion filtrate, in a model of ethanol-induced gastric ulcer in mice, suggesting its possible useful use in the treatment or prevention of gastric ulcer.

Gastroprotective effect and mechanisms of Chinese sumac fruits (Rhus chinensis Mill.) on ethanol-induced gastric ulcers in mice.

This paper aimed to study the effect of the phenol-rich fraction from Chinese sumac fruits on ethanol-induced gastric ulcers in mice and to further elucidate the potential mechanisms. The results showed that the phenol-rich fraction of the fruits significantly decreased the ulcer index, restored the levels of prostaglandin E-2, heat shock protein 70, glutathione and superoxide dismutase, and reduced the malondialdehyde content. Further analyses revealed that the fraction significantly alleviated the gastric oxidative stress by upregulating the Nrf2 protein pathway to increase the HO-1 and NQO1 expression levels, suppressed the inflammation by reducing the expression levels of p-NF-κB and p-IκBα and inhibited the secretion of tumor necrosis factor-α, interleukin-1β, and interleukin-6. In addition, the fraction remarkably prevented gastric mucous cell apoptosis by upregulating Bcl-2 and downregulating Bax and cleaved caspase3. This experiment clarified for the first time that the phenol-rich fraction from Chinese sumac fruits can prevent ethanol-induced gastric ulcers in mice by inhibiting the oxidative stress, inflammatory response and cell apoptosis. The results obtained from the current work indicated that the phenol-rich fraction from Chinese sumac fruits could be applied as a kind of natural resource for producing new functional foods to prevent and/or improve gastric ulcers induced by ethanol.

Protective Effect of Schisandra chinensis Extract Against Ethanol-Induced Gastric Ulcers in Mice by Promoting Anti-inflammatory and Mucosal Defense Mechanisms

Schisandra chinensis (Turcz.) Baill., Schisandraceae, is a common Chinese traditional medicine for the treatment of nervous system disorders and cardiovascular diseases. However, little is known about its efficacy in treating gastrointestinal diseases. In the present study, the protective effect of the ethanol extract of S. chinensis against ethanol-induced acute gastric lesions was investigated in mice. Furthermore, we developed a method based on high-performance liquid chromatography for the quantification of bioactive lignans with a dibenzocyclooctadiene skeleton. The ethanol extract of S. chinensis significantly decreased the ulcer index, sheltered mucosa from lesions, increased levels of superoxide dismutase, decreased malondialdehyde levels, and downregulated plasma levels of tumor necrosis factor-α and interleukin-1β. Our findings demonstrated the gastroprotective properties of the ethanol extract of S. chinensis.