Ethanol-induced Gastric Mucosal Lesions Research Articles

Gastric Mucosal Protective Effects of Cinnamomum cassia in a Rat Model of Ethanol-Induced Gastric Injury.

Cinnamomum cassia (cassia) is a tropical aromatic evergreen tree of the Lauraceae family well known for its fragrance and spicy flavor and widely used in Asian traditional medicine. It has recently garnered attention for its diverse potential health benefits, including anti-inflammatory, anti-cancer, and anti-diabetic properties. However, the gastroprotective effect of C. cassia, particularly against ethanol-induced gastric damage, remains unclear. We investigated the potential gastroprotective property of C. cassia and the underlying mechanisms of action in a rat model of ethanol-induced gastric injury. To assess its effectiveness, rats were fed C. cassia for a 14-day period prior to inducing gastric damage by oral administration of ethanol. Our results indicated that pre-treatment with C. cassia mitigated ethanol-induced gastric mucosal lesions and bleeding. Reduced gastric acid secretion and expression of acid secretion-linked receptors were also observed. Additionally, pretreatment with C. cassia led to decreased levels of inflammatory factors, including TNF-α, p-p65, and IκBα. Notably, C. cassia upregulated the expressions of HO1 and HSP90, with particular emphasis on the enhanced expression of PAS and MUC, the crucial gastric mucosa defense molecules. These findings suggest that C. cassia has protective effects on the gastric mucosa and can effectively reduce oxidative stress and inflammation.

Retraction: Antioxidant Properties and Gastroprotective Effects of 2-(Ethylthio)Benzohydrazones on Ethanol-Induced Acute Gastric Mucosal Lesions in Rats.

Retraction: Antioxidant Properties and Gastroprotective Effects of 2-(Ethylthio)Benzohydrazones on Ethanol-Induced Acute Gastric Mucosal Lesions in Rats.

Prevotella histicola suppresses ferroptosis to mitigate ethanol-induced gastric mucosal lesions in mice

BackgroundEthanol-induced gastric mucosal lesions (EGML) is one of the most common digestive disorders for which current therapies have limited outcomes in clinical practice. Prevotella histicola (P. histicola) has shown probiotic efficacy against arthritis, multiple sclerosis and oestrogen deficiency-induced depression in mice; however, its role in EGML remains unclear in spite of its extensive colonisation of the stomach. Ferroptosis, which is characterised by lipid peroxidation, may be involved in EGML. Herein, we aimed to investigate the effects and underlying mechanism of action of P. histicola on EGML in the ferroptosis-dependent pathway.MethodsP. histicola was intragastrically administered for a week, and deferoxamine (DFO), a ferroptosis inhibitor, was intraperitoneally injected prior to oral ethanol administration. The gastric mucosal lesions and ferroptosis were assessed via histopathological examinations, quantitative real-time PCR, Western blot, immunohistochemistry and immunofluorescence.ResultsP. histicola was originally found to attenuate EGML by reducing histopathological changes and lipid reactive oxygen species (ROS) accumulation. The pro-ferroptotic genes of Transferrin Receptor (TFR1), Solute Carrier Family 39 Member 14 (SLC39A14), Haem Oxygenase-1 (HMOX-1), Acyl-CoA Synthetase Long-chain Family Member 4 (ACSL4), Cyclooxygenase 2 (COX-2) and mitochondrial Voltage-dependent Anion Channels (VDACs) were up-regulated; the anti-ferroptotic System Xc-/Glutathione Peroxidase 4 (GPX4) axis was inhibited after ethanol administration. However, the changes of histopathology and ferroptosis-related parameters induced by ethanol were reversed by DFO. Furthermore, P. histicola treatment significantly downregulated the expression of ACSL4, HMOX-1 and COX-2, as well as TFR1 and SLC39A14, on mRNA or the protein level, while activating the System Xc-/GPX4 axis.ConclusionsWe found that P. histicola reduces ferroptosis to attenuate EGML by inhibiting the ACSL4- and VDAC-dependent pro-ferroptotic pathways and activating the anti-ferroptotic System Xc-/GPX4 axis.

Glucagon-like peptide-2 protects the gastric mucosa via regulating blood flow and metabolites.

Refractory peptic ulcers lead to perforation and hemorrhage, which are fatal. However, these remain a therapeutic challenge. Gastric mucosal blood flow is crucial in maintaining gastric mucosal health. It's reported that Glucagon-like peptide-2 (GLP-2), a gastrointestinal hormone, stimulated intestinal blood flow. However, the direct role of GLP-2 in gastric mucosal blood flow and metabolites remain unclear. Here, we speculated that GLP-2 might protect the gastric mucosa by increasing gastric mucosal blood flow and regulating metabolites. This study was conducted to evaluate the role of GLP-2 in gastric mucosal lesions and its underlying mechanism. We analyzed endogenous GLP-2 during gastric mucosal injury in the serum. Rats were randomly divided into two groups, with 36 rats in each group as follows: (1) normal control group (NC1); (2) ethanol model group (EC1); rats in EC1 and NC1 groups were intragastrically administered ethanol (1 ml/200 g body weight) and distilled water (1 ml/200 g body weight). The serum was collected 10 min before intragastric administration and 15, 30, 60, 90, and 120 min after intragastric administration. Furthermore, additional male Sprague-Dawley rats were randomly divided into three groups, with six rats in each group as follows: (1) normal control group (NC); (2) ethanol model group (EC); (3) 10 μg/200 g body weight GLP-2 group (GLP-2). Rats in the NC and EC groups were intraperitoneally injected with saline. Those in the GLP-2 group were intraperitoneally injected with GLP-2. Thirty minutes later, rats in the EC and GLP-2 groups were intragastrically administered ethanol (1 ml/200 g body weight), and rats in the NC group were intragastrically administered distilled water (1 ml/200 g body weight). After the intragastric administration of ethanol for 1 h, the animals were anesthetized and gastric mucosal blood flow was measured. Serum were collected for ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) metabolomics. There were no significant change in endogenous GLP-2 during gastric mucosal injury (P<0.05). Pretreatment with GLP-2 significantly reduced ethanol-induced gastric mucosal lesions by improving the gastric mucosal blood flow, as examined using a laser Doppler flow meter, Guth Scale, hematoxylin-eosin staining, and two-photon microscopy. UPLC-MS/MS analyses showed that GLP-2 also maintained a steady state of linoleic acid metabolism. Taken together, GLP-2 protects the gastric mucosa against ethanol-induced lesions by improving gastric mucosa blood flow and affecting linoleic acid metabolism.

Gastroprotective mechanism of modified lvdou gancao decoction on ethanol-induced gastric lesions in mice: Involvement of Nrf-2/HO-1/NF-κB signaling pathway.

Modified Lvdou Gancao decoction (MLG), a traditional Chinese medicine formula, has been put into clinical use to treat the diseases of the digestive system for a long run, showing great faculty in gastric protection and anti-inflammatory, whereas its protective mechanisms have not been determined. The current study puts the focus on the protective effect and its possible mechanisms of MLG on ethanol-induced gastric lesions in mice. In addition to various gastric lesion parameters and histopathology analysis, the activities of a list of relevant indicators in gastric mucosa were explored including ALDH, ADH, MDA, T-SOD, GSH-Px, and MPO, and the mechanisms were clarified using RT-qPCR, ELISA Western Blot and immunofluorescence staining. The results showed that MLG treatment induced significant increment of ADH, ALDH, T-SOD, GSH-Px, NO, PGE2 and SS activities in gastric tissues, while MPO, MDA, TNF-α and IL-1β levels were on the decline, both in a dose-dependent manner. In contrast to the model group, the mRNA expression of Nrf-2 and HO-1 in the MLG treated groups showed an upward trend while the NF-κB, TNFα, IL-1β and COX2 in the MLG treated groups had a downward trend simultaneously. Furthermore, the protein levels of p65, p-p65, IκBα, p-IκBα, iNOS, COX2 and p38 were inhibited, while Nrf2, HO-1, SOD1, SOD2 and eNOS were ramped up in MLG treatment groups. Immunofluorescence intensities of Nrf2 and HO-1 in the MLG treated groups were considerably enhanced, with p65 and IκBα diminished simultaneously, exhibiting similar trends to that of qPCR and western blot. To sum up, MLG could significantly ameliorate ethanol-induced gastric mucosal lesions in mice, which might be put down to the activation of alcohol metabolizing enzymes, attenuation of the oxidative damage and inflammatory response to maintain the gastric mucosa. The gastroprotective effect of MLG might be achieved through the diminution of damage factors and the enhancement of defensive factors involving NF-κB/Nrf2/HO-1 signaling pathway. We further confirmed that MLG has strong potential in preventing and treating ethanol-induced gastric lesions.

Gastroprophylactic Effects of p-Cymene in Ethanol-Induced Gastric Ulcer in Rats

The prevalence of gastric ulcers has increased in recent years, mainly because of non-steroidal anti-inflammatory drug utilization. Therefore, the current study investigates the gastroprotective effect of p-Cymene on absolute ethanol-induced acute gastric mucosal hemorrhagic lesions in rats. Thirty Sprague Dawley rats were randomly separated into five groups: normal control, ulcer control, reference, and two experimental groups. The normal and ulcer control groups were orally fed with 0.5% carboxymethylcellulose (CMC). The reference group was fed orally with 20 mg/kg omeprazole. The experimental groups were fed with 30 mg/kg and 60 mg/kg p-Cymene, respectively. After one hour, the normal group was fed with 0.5% CMC, and groups 2–5 were given absolute alcohol. After another hour all rats were sacrificed. The ulcer control group showed severe superficial hemorrhagic gastric mucosal lesions with decreased gastric mucus secretion and pH of gastric content. p-Cymene significantly reduced ethanol-induced gastric lesions, as evidenced by increased mucus and pH of gastric content, decreased ulcer area, reduced or absence of edema, and leucocyte infiltration of the subcutaneous layer. In gastric mucosal homogenate, p-Cymene displayed a significant increase in superoxide dismutase (SOD), catalase (CAT) activities, prostaglandin E2 (PGE2), and significantly reduced the malondialdehyde (MDA) level. In addition, p-Cymene increased the intensity of periodic acid–Schiff (PAS) stain of the gastric epithelium, and produced up-regulation of the HSP 70 protein and down-regulation of the Bax protein of the stomach epithelium, as well as a reduction in the levels of tumor necrotic factor-alpha and interleukin-6, while the level of interleukin-10 was increased. p-Cymene decreased the level of TNF-a and IL-6, and increased the level of IL-10. Acute toxicity with a higher dose of 500 mg/kg p-Cymene did not manifest any toxicological signs in rats and could enhance defensive mechanisms against gastric mucosal lesions. p-Cymene showed gastroprotective effects that could be attributed to its antioxidant nature, or its ability to increase mucus secretion, increase endogenous enzymes (SOD, CAT, PGE2), reduce MDA level, up-regulate HSP 70 protein, down-regulate Bax protein, and modulate inflammatory cytokines.

Polygonum hydropiper extract attenuates ethanol-induced gastric damage through antioxidant and anti-inflammatory pathways.

The present study was conducted to investigate the underlying mechanisms and effective components of Polygonum hydropiper in ethanol-induced acute gastric mucosal lesions. The ethanol extract was purified on an AB-8 macroporous resin column and eluted with 60% ethanol and was then injected into the HPLC system for quantitative analysis. Sprague-Dawley rats were orally pretreated with P. hydropiper extract (PHLE; 50, 100, and 200 mg/kg) for 5 days and then absolute ethanol was administered to induce gastric mucosal damage. One hour after ethanol ingestion, the rats were euthanized and stomach samples were collected for biochemical analysis. Antioxidant enzymes and anti-inflammatory cytokines were quantified. Western blotting was used to detect the expression levels of proteins. Cell proliferation was assayed by CCK-8 assays. The proportion of total flavonoids in the final extract of P. hydropiper was 50.05%, which contained three major bioactive flavonoid constituents, including rutin, quercitrin, and quercetin. PHLE significantly increased cell viability and effectively protected human gastric epithelial cells-1 against alcohol-induced damage in vitro. PHLE pretreatment attenuated gastric mucosal injuries in a dose-dependent manner in rats, and increased the activity of superoxide dismutase, glutathione peroxidase, and glutathione, and decreased the levels of malondialdehyde in gastric tissue. Pretreatment with PHLE also reduced the generation of the pro-inflammatory cytokines tumor necrosis factor-α and interleukin-1β in gastric tissue by downregulating the expression of nuclear factor-kappa B. PHLE exerted protective effects against gastric injury through antioxidant and anti-inflammatory pathways. Flavonoids might be the main effective components of P. hydropiper against gastric mucosal injury.

Protective Effects of Wheat Peptides against Ethanol-Induced Gastric Mucosal Lesions in Rats: Vasodilation and Anti-Inflammation.

Alcohol consumption increases the risk of gastritis and gastric ulcer. Nutritional alternatives are considered for relieving the progression of gastric mucosal lesions instead of conventional drugs that produce side effects. This study was designed to evaluate the gastroprotective effects and investigate the defensive mechanisms of wheat peptides against ethanol-induced acute gastric mucosal injury in rats. Sixty male Sprague–Dawley rats were divided into six groups and orally treated with wheat peptides (0.1, 0.2, 0.4 g/kgbw) and omeprazole (20 mg/kgbw) for 4 weeks, following absolute ethanol administration for 1 h. Pretreatment with wheat peptides obviously enhanced the vasodilation of gastric mucosal blood vessels via improving the gastric mucosal blood flow and elevating the defensive factors nitric oxide (NO) and prostaglandin E2 (PGE2), and lowering the level of vasoconstrictor factor endothelin (ET)-1. Wheat peptides exhibited anti-inflammatory reaction through decreasing inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6, and increasing trefoil factor 1 (TFF1) levels. Moreover, wheat peptides significantly down-regulated the expression of phosphorylated nuclear factor kappa-B (p-NF-κB) p65 proteins in the NF-κB signaling pathway. Altogether, wheat peptides protect gastric mucosa from ethanol-induced lesions in rats via improving the gastric microcirculation and inhibiting inflammation mediated by the NF-κB signaling transduction pathway.

Research on the structural characteristics of a novel Chinese Iron Yam polysaccharide and its gastroprotection mechanism against ethanol-induced gastric mucosal lesion in a BALB/c mouse model.

In this study, a triple-helix Chinese Iron Yam polysaccharide (CIYP) with a molecular weight of 1.67 × 103 kDa was obtained. The CIYP was extracted with deionized water followed by deproteination, decoloration and purification using anion-exchange chromatography and size exclusion chromatography. Its structural characteristics and micromorphology were investigated by GC-MS, periodate oxidation and Smith degradation, FT-IR, NMR spectroscopy, SEM and AFM. The results showed that CIYP is a catenarian polysaccharide composed of rhamnose, arabinose, mannose, glucose, galactose and galacturonic acid in the ratio of 1 : 1.33 : 8.31 : 2.83 : 1.12 : 2.62. Meanwhile, the gastric mucosa protective effect of CIYP on an ethanol-injured BALB/c mouse model was investigated. It was found that the preventive CIYP-treatment groups (200 and 400 mg kg-1 d-1) showed gastric mucosa protective effects on the BALB/c mouse model. The lesion index and lesion inhibition rate of the CIYP and cimetidine treatment groups were significantly altered compared with the ethanol-induced gastric mucosal lesion (GML) group. Moreover, the administration of CIYP showed definite effects of increasing the NO, PGE2 and EGF levels, and SOD activities, and reducing the MDA levels of gastric mucosa tissues to prevent gastric oxidative stress. Histopathological analysis indicated that the microscopic morphology of gastric mucosal tissues was changed after being damaged by ethanol and the damage was significantly reduced after CIYP administration. Finally, the western blot and quantitative real-time polymerase chain reaction (qRT-PCR) results provided comprehensive evidence that the CIYP could repress gastric inflammation through the reduction of IL-1β, TNF-α and IL-6, prevent gastric oxidative stress through the inhibition of lipid peroxides, and favor cell survival via downregulating the TAK1, MKK3, P-p38 and Bax levels and upregulating the protein expression levels, compared with the CIM group.

Dynamic observation and analysis of metabolic response to moxibustion stimulation on ethanol-induced gastric mucosal lesions (GML) rats

BackgroundGastric mucosal lesion (GML) is the initiating pathological process in many refractory gastric diseases. And moxibustion is an increasingly popular alternative therapy that prevents and treats diseases. However, there are few published reports about developing pathology of GML and therapeutic mechanism of moxibustion treatment on GML. In this study, we investigated pathology of GML and therapeutic mechanism of moxibustion treatment on GML.MethodsThe male Sprague-Dawley (SD) rats were induced by intragastric administration of 75% ethanol after fasting for 24 h and treated by moxibustion at Zusanli (ST36) and Liangmen (ST21) for 1 day, 4 days or 7 days. Then we applied 1H NMR-based metabolomics to dynamic analysis of metabolic profiles in biological samples (stomach, cerebral cortex and medulla). And the conventional histopathological examinations as well as metabolic pathways assays were also performed.ResultsMoxibustion intervention showed a beneficial effect on GML by modulating comprehensive metabolic alterations caused by GML, including energy metabolism, membrane metabolism, cellular active and neurotransmitters function.ConclusionsMoxibustion can effectively treat gastric mucosal damage and effectively regulate the concentration of some related differential metabolites to maintain the stability of the metabolic pathway.

Chemical characterization and gastroprotective effect of an isolated polysaccharide fraction from Bletilla striata against ethanol-induced acute gastric ulcer

The chemical characterization and protective role against ethanol-induced gastric ulcerated rats of a polysaccharide fraction from Bletilla striata (BSP) collected by ultrafiltration membrane approach were evaluated. This BSP faction was consisted of mannose and glucose at a molar ratio of 2.4:1 approximately, with a molecular weight of 146 KDa. FT-IR, NMR and XRD spectra indicated that BSP faction contained α-Man and β-Glc residues with low overall crystallinity. The polysaccharide exhibited significant scavenging activities of ABTS and FRAP, as well as non-toxicity against human gastric epithelial GES-1 cells. Oral administration with 100 mg/kg of BSP for 3 days continuously could significantly prevent the formation of ethanol-induced gastric mucosal lesion. It could also reduce the levels of pro-inflammatory cytokines, including TNF-α, IL-1β, IL-6, and IL-18, and MPO activity in gastric tissue. Additionally, the BSP faction exhibited antioxidant activity, increased the content of PEG2 as a defensive factor, and suppressed MAPK/NF-κB signaling pathway in gastric tissue. These results indicated that the gastroprotective activity of BSP faction could be attributed to the reduction of pro-inflammatory cytokines and oxidative stress and the inhibition of MAPK/NF-κB pathways. Our results provided substantial evidence that BSP could be a promising phytomedicine for gastric ulcer prevention.

Protective effect of Corchorus capsularis L. leaves on ethanol-induced acute gastric mucosal lesion in rats.

In Taiwan, Corchorus capsularis L. has long been cultivated and the leaves are consumed as edible vegetable. This study is to investigate the protection effect of extract of C. capsularis leaves (ECC) on ethanol-induced acute gastric mucosal lesion (AGML) in rats. The results of phytochemical determination in ECC for total polyphenol, flavonoid and polysaccharide were 59.88 ± 0.61 mg/g, 86.39 ± 18.0 mg/g and 320.89 ± 6.99 mg/g, respectively. ECC showed significant activity of 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging with IC50 of 0.25 mg/ml. In vivo studies, Sprague-Dawley (SD) rats were randomly divided into five groups: sham, vehicle (control) and low-, medium-, and high-dose ECC (LECC, MECC, HECC; 200, 400, and 1,000 mg/kg/day, respectively). ECC was able to decrease significantly the ulcer index (UI) caused by 80% ethanol in a dose dependent manner. There was no significant effect on growth trend and food intake rate after the administration of ECC in the experimental period. The serum lipid parameters in ECC groups revealed significant increase in glutathione peroxidase (GPx), superoxide dilmutase (SOD) and catalase (CAT), and a decrease in malondialdehyde (MDA). Significant amelioration on pathological lesion score was found in ECC groups compared with the control group (P<0.05). The overall results indicate that ECC has protective effects on ethanol-induced AGML in rats, which could be associated with its antioxidant activity.

Alterations in Gastric Mucosal Expression of Calcitonin Gene-Related Peptides, Vanilloid Receptors, and Heme Oxygenase-1 Mediate Gastroprotective Action of Carbon Monoxide against Ethanol-Induced Gastric Mucosal Lesions.

Carbon monoxide (CO) has been reported to contribute to the maintenance of gastric mucosal integrity, gastroprotection, and ulcer healing. However, involvement of transient receptor potential vanilloid receptor type 1 (TRPV1) located on afferent sensory fibers endings and sensory neuropeptide calcitonin gene-related peptide (CGRP) in CO-mediated gastroprotection against ethanol-induced gastric damage has not been explored. Male Wistar rats with and without denervation of afferent sensory neurons induced by capsaicin (total dose 125 mg/kg within 3 days) were pretreated with vehicle, CO donor tricarbonyldichlororuthenium (II) dimer (CORM-2, 5 mg/kg i.g.), administered alone or with CGRP-α (10 μg/kg i.p.) or TRPV1 antagonist capsazepine (5 mg/kg i.g.), followed 30 min later by intragastric (i.g.) administration of 75% ethanol. The area of gastric damage and gastric blood flow (GBF) were assessed planimetrically and by laser flowmetry, respectively. Microscopic evaluation of ethanol-induced gastric lesions was performed after haematoxylin/eosin (H&E) or alcian blue/periodic acid-Schiff/alcian blue (AB/PAS) staining. Gastric mucosal mRNA fold change for heme oxygenase (HMOX)-1, HMOX-2, CGRP-α, CGRP-β, inducible nitric oxide synthase (iNOS), endothelial (e)NOS, neuronal (n)NOS, cyclooxygenase (COX)-1, COX-2, and protein expression for HMOX-1 and TRPV1 was determined by real-time PCR or Western blot, respectively. Pretreatment with CORM-2 combined or not with CGRP reduced ethanol-induced gastric lesions and elevated GBF. Capsaicin-denervation or co-treatment with capsazepine or CGRP and CORM-2 in capsaicin-denervated animals failed to affect these beneficial effects of CO donor. In rats with intact sensory nerves, CORM-2 increased gastric mRNA level for HMOX-1 and CGRP-α. In capsaicin-denervated rats, CORM-2 increased eNOS mRNA fold change and TRPV1 protein expression while capsaicin denervation itself decreased HMOX-1 protein expression and eNOS mRNA level. We conclude that CO prevents gastric mucosa from ethanol-induced lesions due to activation of TRPV1/CGRP-α system and accompanying increase in gastric microcirculation but independently on afferent sensory nerve activity despite the stimulation of TRPV1 protein and CGRP-α mRNA expression.

Evaluation of Gastroprotective Effect of Vanadyl Sulfate and Lycopene on rat model with Ethanol-Induced Gastric Mucosal Lesions

Gastric ulcers result from an imbalance between endogenous defense mechanisms and certain aggressive agents. Many drugs were used to overcome this imbalance, but few literatures made on plants. Therefore, we try to evaluate the gastroprotective efficacy of two nutritional supplements (Vanadyl sulfate and Lycopene) in comparison to Lansoprazole. Five groups of seven healthy albino male rats each were received an oral daily dose of above agents for ten days. Then 1.25 ml of 95% ethanol orally used to induce mucosal injury and animals were sacrificed 1 hour later. Glutathione and malondialdehyde were estimated. A significant elevation in glutathione level found in Vanadyl and Lycopene-received groups in comparison to lansoprazole-received group (717.13±19.47 μmol/gm wet tissue, 609.55±17.6 μmol/gm wet tissue and 512.07±25.32 μmol/gm wet tissue respectively), with a significant reduction in malondialdehyde level (10.63±0.92 nmol/gm wet tissue, 12.66±0.56 nmol/g wet tissue and 14.90±0.33 nmol/gm wet tissue respectively). This revealed gastro-protective effects of Vanadyl and Lycopene in ameliorating the oxidative cellular damage.

Gastroprotective activity of polysaccharide from Hericium erinaceus against ethanol-induced gastric mucosal lesion and pylorus ligation-induced gastric ulcer, and its antioxidant activities

The gastroprotective activity of Hericium erinaceus polysaccharide was investigated in rats. The antioxidant activities were also evaluated. Pre-treatment of polysaccharide could reduce ethanol-induced gastric mucosal lesion and pylorus ligation-induced gastric ulcer. The polysaccharide exhibited scavenging activities of 1, 1-diphenyl-2-picryl-hydrozyl and hydroxyl radicals, and ferrous ion-chelating ability. In the pylorus ligation-induced model, gastric secretions (volume of gastric juice, gastric acid, pepsin and mucus) of ulcer rats administrated with polysaccharide were regulated. Levels of tumor necrosis factor-α and interleukins-1β in serum, and myeloperoxidase activity of gastric tissue were reduced, while antioxidant status of gastric tissue was improved. Defensive factors (nitric oxide, prostaglandin E2, epidermal growth factor) in gastric tissue were increased. These results indicate that Hericium erinaceus polysaccharide possess gastroprotective activity, and the possible mechanisms are related to its regulations of gastric secretions, improvements of anti-inflammatory and antioxidant status, as well as increments of defensive factors releases.

Short Chain Fatty Acid Acetate Protects against Ethanol-Induced Acute Gastric Mucosal Lesion in Mice

Short Chain Fatty Acid Acetate Protects against Ethanol-Induced Acute Gastric Mucosal Lesion in Mice

Gastroprotective effects of Tunisian green clay on ethanol-induced gastric mucosal lesion in rats

Natural green clay is mostly used in pharmaceutical and cosmetic products. The effect of this raw material from different outcrops around the world demonstrates its beneficial role on human health. The green clay from southern Tunisia is widely used in local traditional medicine and cosmetic preparations but its biological activity in vivo has not been studied yet. For this reason, this work was interested in deciphering the properties of the Tunisian green clay such as mineralogy composition and biological effect. In fact, the mineralogical study of this green clay shows two types of clay minerals such as illite and kaolinite with proportion of 75% and 25%, respectively. In order to study the biological effect, green clay was administered orally to rats for 1h at 50, 75, 100 and 125mg/kg doses. After that, ethanol 95% was given to these rats to induce a gastric ulcer. Then, several parameters (e.g. Ulcer index, protective rate, mucus production gastric and mucosa histology) were measured to evaluate the gastroprotective activity. The histology study shows normal gastric mucosa in rats pretreated at 75, 100 and 125mg/kg doses and the decrease of Ulcer Index (%I=97%) and lesions areas.The oral administing mixture of Tunisian green clay with ethanol in rats induces severe mucosal lesion and hemorrhagic bands. This clay colored by methylene blue shows that clay was linked to the mucus excreted by the stomach surface. The green clay didn't neutralize ethanol gastro toxicity and formed a layer on the gastric mucosa to protect it by a mechanical action. When investigated on rats at an effective dose treatment (75mg/kg) for 30days, the subchronic toxicity test of green clay did not reveal any signs of mortality and toxicity, and it demonstrated the normal hematological and biochemical parameters of rats.Thus, the Tunisian green clay can be considered as a safe natural product since it has a potential gastroprotective activity on ethanol induced gastric mucosal lesions in rats.

Mechanisms of curcumin-induced gastroprotection against ethanol-induced gastric mucosal lesions

BackgroundCurcumin, a pleiotropic substance used for centuries in traditional medicine, exhibits antioxidant, anti-inflammatory and antiproliferative efficacy against various tumours, but the role of curcumin in gastroprotection is little studied. We determined the effect of curcumin against gastric haemorrhagic lesions induced by 75% ethanol and alterations in gastric blood flow (GBF) in rats with cyclooxygenase-1 (COX-1) and COX-2 activity inhibited by indomethacin, SC-560 or rofecoxib, inhibited NO-synthase activity, capsaicin denervation and blockade of TRPV1 receptors by capsazepine.MethodsOne hour after ethanol administration, the gastric mucosal lesions were assessed by planimetry, the GBF was examined by H2 gas clearance, plasma gastrin was determined by radioimmunoassay, and the gastric mucosal mRNA expression of Cdx-2, HIF-1α, HO-1 and SOD 2 was analysed by RT-PCR.ResultsCurcumin, in a dose-dependent manner, reduced ethanol-induced gastric lesions and significantly increased GBF and plasma gastrin levels. Curcumin-induced protection was completely reversed by indomethacin and SC-560, and significantly attenuated by rofecoxib, L-NNA, capsaicin denervation and capsazepine. Curcumin downregulated Cdx-2 and Hif-1α mRNA expression and upregulated HO-1 and SOD 2, and these effects were reversed by L-NNA and further restored by co-treatment of L-NNA with l-arginine.ConclusionsCurcumin-induced protection against ethanol damage involves endogenous PG, NO, gastrin and CGRP released from sensory nerves due to activation of the vanilloid TRPV1 receptor. This protective effect can be attributed to the inhibition of HIF-1α and Cdx-2 expression and the activation of HO-1 and SOD 2 expression.

English

English

Preparation, Characterization and Anti-Ulcer Efficacy of Sanguinarine Loaded Solid Lipid Nanoparticles

Aim: This study was designed to develop sanguinarine-loaded solid lipid nanoparticles (SG-SLNs) and investigate its gastroprotective effect on ethanol-induced gastric mucosal lesions in mice. Methods: SG-SLNs were prepared by high temperature melt-cool solidification method using glycerol monostearate as the lipid and a combination of lecithin with poloxamer 188 as the surfactants. Solid lipid nanoparticles (SLNs) were designed at varying lipid concentrations (5, 10, 15, and 20 mg/mL), surfactant mixture concentrations (6, 12, and 18 mg/mL), and drug contents (5, 10, 15, and 20 mg/mL) in “one factor at a time” fashion. Ethanol-induced gastric ulcer model was performed on Kunming mice to examine the anti-inflammatory activity of SG-SLNs and compare it with sanguinarine (SG). Results: The high temperature melt-cool solidification method provided consistent production of SLNs with smaller size and high entrapment efficiency (EE%). The composition of optimal formulation was 10 mg/mL lipid concentration, 18 mg/mL surfactant mixture concentration, and 15 mg/mL drug amount. The mean particle size and EE% of optimized formulation were 238 ± 10.9 nm and 79 ± 2.8%, respectively. Additionally, SG-SLNs significantly decreased tumor necrosis factor-alpha and interleukin-6 levels in the serum and gastric tissue, and reduced the content of NO in serum, and strengthened the protection of mucosal membrane. Moreover, SG-SLNs treatment markedly inhibited ethanol-induced nuclear factor-kappa B (NF-κB) activation when compared with SG. Conclusions: SLNs could be potentially applied as a delivery system of SG. The protective effect of SG-SLNs is due to the suppression of NF-κB expression and subsequent pro-inflammatory cytokines release.