Ethanol-induced Gastric Mucosal Damage Research Articles

Pretreatment with Dan-Shen-Yin granules alleviates ethanol-induced gastric mucosal damage in rats by inhibiting oxidative stress and apoptosis via Akt/Nrf2 signaling pathway

BackgroundGastric ulcer (GU) is a common gastrointestinal disease with high morbidity that may be caused by various pathogenic factors. Dan-Shen-Yin (DSY), a traditional prescription, improves myocardial and gastrointestinal functions; however, its effect on GU and the underlying mechanisms requires further research. PurposeWe aimed to evaluate the pharmacodynamics of DSY granules in GU using three different animal models and explore their potential mechanisms. MethodsDSY granules were manufactured and subjected to quality control by high-performance liquid chromatography (HPLC). Three GU models were established using ethanol, aspirin, or water immersion restraint combined with aspirin and examined using the Guth method and hematoxylin and eosin (H&E) staining. The effects of DSY granules on gastric mucosal glycoproteins and the release of defensive and aggressive factors in ethanol-induced GU were measured using periodic acid-Schiff (PAS) staining and ELISA. TUNEL staining and detection of apoptosis-related proteins were used to evaluate the role of DSY granules on apoptosis. Potential mechanisms were predicted using network pharmacology, molecular docking, and western blot to verify the related targets and pathways. ResultsDSY granules were prepared for the first time and quality control standard was established. Pharmacodynamic evaluation indicated that DSY granules significantly reduced the GU index and gastric mucosal injury in the three GU models, and the GU inhibition rate of DSY granules was superior to omeprazole in ethanol-induced GU model (60.32% vs 21.96%). Further studies in ethanol-induced GU model revealed that DSY granules increased the levels of the defensive factors (PGE2, NO, SOD, CAT, TAOC, and GSH) and decreased the levels of aggressive factors (MDA, TNF-α, and IL-1β), thereby inhibiting oxidative stress and inflammation, attenuating gastric mucosal injury. Moreover, the results of TUNEL staining and western blot showed that DSY granules suppressed apoptosis by reducing the ratios of Bax/Bcl-2 and cleaved-Caspase-3/Caspase-3. In addition, the results of network pharmacology and molecular docking suggested that the mechanisms of DSY granules against GU may be related to the Akt-related signaling pathway. Further study confirmed that DSY granules significantly reduced the ratio of p-Akt/Akt and promoted the expression of Nrf2 and NQO1, protecting the gastric mucosa. ConclusionsOur results indicated that DSY granules had protective effects on GU caused by different mechanisms, especially ethanol-induced GU. DSY granules alleviated gastric mucosal damage by inhibiting oxidative stress, inflammation, and apoptosis, which may be associated with the regulation of Akt/Nrf2 signaling pathway. Therefore, DSY granules may be a promising drug for the treatment of GU.

Pretreatment with Dan-Shen-Yin granules alleviates ethanol-induced gastric mucosal damage in rats by inhibiting oxidative stress and apoptosis via Akt/Nrf2 signaling pathway

BackgroundGastric ulcer (GU) is a common gastrointestinal disease with high morbidity that may be caused by various pathogenic factors. Dan-Shen-Yin (DSY), a traditional prescription, improves myocardial and gastrointestinal functions; however, its effect on GU and the underlying mechanisms requires further research. PurposeWe aimed to evaluate the pharmacodynamics of DSY granules in GU using three different animal models and explore their potential mechanisms. MethodsDSY granules were manufactured and subjected to quality control by high-performance liquid chromatography (HPLC). Three GU models were established using ethanol, aspirin, or water immersion restraint combined with aspirin and examined using the Guth method and hematoxylin and eosin (H&E) staining. The effects of DSY granules on gastric mucosal glycoproteins and the release of defensive and aggressive factors in ethanol-induced GU were measured using periodic acid-Schiff (PAS) staining and ELISA. TUNEL staining and detection of apoptosis-related proteins were used to evaluate the role of DSY granules on apoptosis. Potential mechanisms were predicted using network pharmacology, molecular docking, and western blot to verify the related targets and pathways. ResultsDSY granules were prepared for the first time and quality control standard was established. Pharmacodynamic evaluation indicated that DSY granules significantly reduced the GU index and gastric mucosal injury in the three GU models, and the GU inhibition rate of DSY granules was superior to omeprazole in ethanol-induced GU model (60.32% vs 21.96%). Further studies in ethanol-induced GU model revealed that DSY granules increased the levels of the defensive factors (PGE2, NO, SOD, CAT, TAOC, and GSH) and decreased the levels of aggressive factors (MDA, TNF-α, and IL-1β), thereby inhibiting oxidative stress and inflammation, attenuating gastric mucosal injury. Moreover, the results of TUNEL staining and western blot showed that DSY granules suppressed apoptosis by reducing the ratios of Bax/Bcl-2 and cleaved-Caspase-3/Caspase-3. In addition, the results of network pharmacology and molecular docking suggested that the mechanisms of DSY granules against GU may be related to the Akt-related signaling pathway. Further study confirmed that DSY granules significantly reduced the ratio of p-Akt/Akt and promoted the expression of Nrf2 and NQO1, protecting the gastric mucosa. ConclusionsOur results indicated that DSY granules had protective effects on GU caused by different mechanisms, especially ethanol-induced GU. DSY granules alleviated gastric mucosal damage by inhibiting oxidative stress, inflammation, and apoptosis, which may be associated with the regulation of Akt/Nrf2 signaling pathway. Therefore, DSY granules may be a promising drug for the treatment of GU.

The Gastroprotective Effect of Walnut Peptides: Mechanisms and Impact on Ethanol-Induced Acute Gastric Mucosal Injury in Mice

The objective of this research was to explore the protective impact of walnut peptides (WP) against ethanol-induced acute gastric mucosal injury in mice and to investigate the underlying defense mechanisms. Sixty male BALB-c mice were divided into five groups, and they were orally administered distilled water, walnut peptides (200 and 400 mg/kg bw), and omeprazole (20 mg/kg bw) for 24 days. Acute gastric mucosal injury was then induced with 75% ethanol in all groups of mice except the blank control group. Walnut peptides had significant protective and restorative effects on tissue indices of ethanol-induced gastric mucosal damage, with potential gastric anti-ulcer effects. Walnut peptides significantly inhibited the excessive accumulation of alanine aminotransferase (ALT), aspartate transferase (AST), and malondialdehyde (MDA), while promoting the expression of reduced glutathione (GSH), total antioxidant capacity (T-AOC), glutathione disulfide (GSSG), and mouse epidermal growth factor (EGF). Furthermore, the Western blot analysis results revealed that walnut peptides significantly upregulated the expression of HO-1 and NQO1 proteins in the Nrf2 signaling pathway. The defensive impact of walnut peptides on the gastric mucosa may be achieved by mitigating the excessive generation of lipid peroxides and by boosting cellular antioxidant activity.

Protection by gabapentin against indomethacin and ethanol-induced gastric mucosal damage in the rat. A histological and histochemical study

Protection by gabapentin against indomethacin and ethanol-induced gastric mucosal damage in the rat. A histological and histochemical study

Melanin from Sepia pharaonis ink alleviates mucosal damage and reduces inflammation to prevent alcohol-induced gastric ulcers

Melanin (MSI) is the primary component of Sepia pharaonis ink. Studies have demonstrated melanin's anti-inflammatory and antioxidant activities in colitis. In the present study, the protective effect of ink melanin against ethanol-induced gastric mucosal damage in mice was investigated. After oral administration of MSI for 12 days, the mice were treated with anhydrous ethanol (0.2 mL) to establish the gastric ulcer model. Histopathological analysis showed that MSI reduced the ulcer area and bleeding symptoms of gastric tissue. MSI exhibited significant antioxidant properties by upregulating superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) activities and decreasing malondialdehyde (MDA) content. The expression levels of epidermal growth factor (EGF), epidermal growth factor receptor (EGFR), and prostaglandin E−2 (PGE2) significantly decreased during gastric mucosal injury, while MSI significantly reversed the effects. Furthermore, MSI reduced the expression of inflammatory factors tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) and the protein expression of toll-like receptor 4 (TLR4), p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal-regulated protein kinases 1/2 (ERK1/2). In addition, MSI repressed gastric cell apoptosis by decreasing the expression of Caspase-3. In conclusion, MSI alleviated ethanol-induced gastric ulcer injury by modulating oxidation stress and inflammatory cytokines and maintaining the mucosal barrier, which can be used as therapeutic functional food or nutritional supplement to prevent gastric ulcers. Meanwhile, the mechanism of MSI targeted gastric TLR4/MAPKs pathway deserves further verification.

Gastroprotective effect of Zinnia elegans extracts against ethanol-induced gastric mucosal damage through downregulation of TLR4 and inflammatory cytokines

Background: One of the most common gastrointestinal diseases is gastric ulcer (GU). The ethanolic extract from the aerial part of Zinnia elegans was created to test its ability to protect the gastric mucosa from damage caused by ethanol in mice. Method: Zinnia elegans ethanolic extract was administrated intragastrically once daily for three days. After the final intragastric dose, gastric ulcer in mice was created on the third day using 70% ethanol. The stomach tissues were extracted to assess the severity of the gastric mucosal changes. Results: Orally administered Zinnia elegans ethanolic extract reduced the severity of stomach mucosal changes. In addition, the levels of tumor necrosis factor‐α (TNF‐α), interleukin-1B (IL‐1β), and tool-like receptor (TLR4) activity in stomach tissues were all dramatically reduced after oral administration of the extract. These findings demonstrate that the anti-inflammatory properties of Zinnia elegans ethanolic extract protect against ethanol-induced stomach mucosal damage in mice. Conclusions: The results of this investigation offer some support for the creation of new treatments for stomach ulcers as an alternative to treating gastric damage brought on by alcohol consumption.

Evidence of anti-inflammatory and anti-ulcer properties of aerial parts of Centaurea tougourensis Boiss. and Reut.

Purpose: To determine the anti-inflammatory and anti-ulcer properties of the aerial parts of Centaurea tougourensis Boiss. & Reut.
 Methods: The effects of n-butanol (n-BuOH) extract of the aerial part of Centaurea tougourensis on carrageenan-induced paw edema and ethanol-induced gastric mucosal damage were determined at 2 doses (200 and 400 mg/kg, po) in a mouse model. For each test, the animals were randomly divided into negative and positive control groups, as well as extract-treated groups. The mice were observed for any sign of inflammation for a period of 24h.
 Results: Reduction of paw edema by C. tougourensis extract was highly significant (p < 0.001) at a dose of 400 mg/kg 24 h after carrageenan injection, with 55.26 % inhibition, followed very closely by 53.15 % inhibition at the dose of 200 mg/kg; indomethacin group showed an inhibition of 60 %. Histological examination supported the inhibition results. A significant reduction in inflammation by the extract at a dose of 400 mg/kg was also observed. No sign of ulcer was observed with C. tougourensis at the two doses (200 and 400 mg/kg). The total polyphenol content of the n-BuOH extract was 85.44 цg gallic acid equivalent/mg of extract. Tannins were the most abundant fraction (51.87 цg tannic acid equivalent/mg of extract), followed by flavonoids (25.55 цg quercetin equivalent/mg of extract).
 Conclusion: The results indicate that C. tougourensis may have potential beneficial effects in the treatment of diseases associated with inflammation and pain, besides its protective effect on the gastrointestinal tract.

Terazosin Stimulates Pgk1 to Remedy Gastrointestinal Disorders.

Gastrointestinal disease is the most common health concern that occurs due to environmental, infectious, immunological, psychological, and genetic stress. Among them, the most frequent diseases are gastric ulcer (GU) and ulcerative colitis (UC). DSS-induced UC and ethanol-stimulated GU models resemble the pathophysiology of human gastrointestinal disease. The current study was designed to explore the anti-oxidation, anti-inflammation, anti-cell death properties of terazosin, an α-adrenergic receptor antagonist, in vivo and in vitro. Our results indicate that terazosin dramatically activates Pgk1, and upregulates glycose metabolism, evidenced by the enhanced ATP production and higher LDH enzymatic activity. Also, terazosin significantly enhances p-AKT expression and inhibits NF-κB p65 activation through abrogating the phosphorylation of IKBα, as well as lowers Caspase-1 and GSDMD expression. The findings in this study demonstrate that terazosin exhibits anti-inflammatory effects by downregulating NF-κB-GSDMD signal pathway, along with enhancing glycolysis for gastrointestinal disease treatment. Meanwhile, we also find terazosin ameliorates ethanol-induced gastric mucosal damage in mice. Collectively, as a clinical drug, terazosin should be translated into therapeutics for gastrointestinal disease soon.

Activation of AMPK/mTOR-driven autophagy and inhibition of NLRP3 inflammasome by saxagliptin ameliorate ethanol-induced gastric mucosal damage

AimsSaxagliptin, a selective/potent dipeptidyl peptidase-4 inhibitor, has revealed remarkable anti-inflammatory features in murine models of nephrotoxicity, hepatic injury, and neuroinflammation. However, its potential effect on ethanol-induced gastric mucosal injury has not been examined. Hence, the present work investigated the prospect of saxagliptin to attenuate ethanol-evoked gastric injury, with emphasis on the AMPK/mTOR-driven autophagy and NLRP3/ASC/caspase-1 pathway. Materials and methodsIn ethanol-induced gastropathy, the gastric tissues were examined by immunohistochemistry, immunoblotting, histopathology, and ELISA. Key findingsThe results demonstrated that saxagliptin (10 mg/kg; by gavage) suppressed the gastric pathological signs (area of gastric ulcer and ulcer index scores), histopathologic aberrations/damage scores, without provoking hypoglycemia in rats. These protective features were attributed to the enhancement of gastric mucosal autophagy flux, as proven with increased expression of LC3-II and Beclin 1, decreased accumulation of p62 SQSTM1, and activation of the autophagy-linked AMPK/mTOR pathway by increasing the expression of p-AMPK/AMPK and decreasing the expression of the autophagy suppressor p-mTOR/mTOR signal. In tandem, saxagliptin counteracted the ethanol-induced pro-apoptotic events by downregulating Bax, upregulating Bcl2 protein, and lowering the Bax/Bcl2 ratio. Equally important, saxagliptin suppressed the NLRP3 inflammasome in the gastric tissue by lowering the expression of NLRP3, ASC, and nuclear NF-κBp65, decreasing the activity of caspase-1, and diminishing the IL-1β levels. In the same regard, saxagliptin suppressed the mucosal oxidative stress by lowering lipid peroxide levels, increasing GSH and GPx antioxidants, and activating Nrf2/HO-1 pathway. SignificanceSaxagliptin may be a promising intervention against ethanol-evoked gastropathy by activating AMPK/mTOR-driven autophagy and inhibiting NLRP3 inflammasome.

Gastroprotective Effect of Ethanol Extracts from Bark of Magnolia officinalis on Ethanol-Induced Gastric Mucosal Damage in Rats.

Background. Magnolia officinalis Rehd. and Wils. is widely used in Asian countries because of its multiple pharmacological effects. This study investigated the gastroprotective effect and mechanisms of the ethanol extracts from the bark of Magnolia officinalis (MOE) against ethanol-induced gastric mucosal damage in rats. Methods. MOE was prepared by reflux extraction with 70% ethanol, and its main compounds were analyzed by UPLC-Q-Exactive Orbitrap-MS. DPPH, ABTS, and FRAP methods were used to evaluate the antioxidant capacity of MOE in vitro. The gastroprotective effects of MOE were evaluated by the area of gastric injury, H&E (hematoxylin-eosin), and PAS (periodic acid-Schiff). The mechanism was explored by measuring the levels of cytokines and protein in the NF-κB signaling pathway. Results. 30 compounds were identified from MOE, mainly including lignans and alkaloids. MOE presented a high antioxidant activity in several oxidant in vitro systems. Gastric ulcer index and histological examination showed that MOE reduced ethanol-induced gastric mucosal injury in a dose-dependent manner. MOE pretreatment significantly restored the depleted activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) enzymes, reduced malondialdehyde (MDA), and prostaglandin E2 (PGE2) levels in the gastric tissue in rats. In addition, MOE also inhibited the activation of nuclear factor kappa B (NF-κB) pathway and decreased the production of proinflammatory cytokines. Conclusions. The gastroprotective effect of MOE was attributed to the inhibition of oxidative stress and the NF-κB inflammatory pathway. The results provided substantial evidence that MOE could be a promising phytomedicine for gastric ulcer prevention.

Caffeic acid attenuates gastric mucosal damage induced by ethanol in rats via nitric oxide modulation

Anti-oxidant and anti-inflammatory properties of caffeic acid (CA) have been reported recently. In this study, the therapeutic effects of CA on ethanol-induced ulcer and the roles of nitric oxide and cholinergic pathways in these effects were investigated. Ulcer was induced by ethanol via oral gavage. Ulcer induced rats were treated with either vehicle (ulcer group) or CA (100, 250 or 500 mg/kg, per oral gavage). Macroscopic evaluation showed that 250 mg/kg CA was the effective dose. To elucidate the action mechanism of CA, 10 mg/kg l-NAME or 1 mg/kg atropine sulfate was administered to 250 mg/kg CA treated groups. All rats were decapitated 1 h after ulcer induction and gastric samples were scored macroscopically and microscopically, and analyzed for myeloperoxidase (MPO), malondialdehyde (MDA), and glutathione (GSH) levels. ANOVA test was used for statistical analyses. Macroscopic and microscopic damage scores, MDA levels and MPO activity were increased while GSH levels were decreased in ulcer group. Treatment with 250 mg/kg and 500 mg/kg CA reduced macroscopic and microscopic damage scores, decreased MPO activity and MDA levels, and preserved the depleted glutathione significantly. l-NAME administration before CA treatment elevated MDA levels, MPO activity and depleted glutathione. However, atropine sulfate had no effect on biochemical parameters.We conclude that CA ameliorates ethanol-induced gastric mucosal damage, and NO pathway contributes to this effect. On the other hand, there is a lack of evidence for the contribution of the muscarinic cholinergic system.

Wheat peptide protects against ethanol-induced gastric mucosal damage through downregulation of TLR4 and MAPK

• Excessive alcohol consumption can lead to gastric mucosal damage. • Wheat peptides repressed gastric inflammation through the reduction of inflammatory factor. • Wheat peptides prevented gastric oxidative stress through the inhibition of lipid peroxides. • Wheat peptides down-regulated protein expression levels of TLR4, MAPK and ERK. • Ethanol-induced gastric mucosal damage in rats can be prevented by wheat peptides. Excessive alcohol consumption can induce gastric mucosal damage. The present work aimed to examine the protective effect of wheat peptides against ethanol-induced gastric mucosal damage in rats. Wheat peptides (WP) were administered daily by gavage for 30 days before the rats were treated with anhydrous ethanol (1 mL). Histological observations were performed, as well as the anti-oxidation effect and anti-inflammatory action. WP increased the superoxide dismutase activity and prostaglandin E-2 (PGE2) levels and decreased the malondialdehyde and interleukin-8 (IL-8) levels. WP suppressed gastric mucosa inflammation through the reduction of TNF-α, MPO, IL-6, and IL-1β. WP repressed the expression of caspase-3, and enhanced the expression of anti-apoptotic protein EGFR. Furthermore, WP down-regulated protein expression levels of TLR4, MAPK and ERK, suggesting that WP have a potential effect to inhibit ethanol-induced inflammatory responses via blocking TLR4/MAPK/ERK signal transduction. The potential mechanism may be associated with enhancement of antioxidation, anti-inflammatory action and anti-apoptosis function.

Flavonoid-Rich Extract of Dissotis rotundifolia Whole Plant Protects against Ethanol-Induced Gastric Mucosal Damage.

Dissotis rotundifolia is a plant in the family Melastomataceae. The methanolic extract of the whole plant is reported to be rich in C-glycosylflavones such as vitexin and orientin. Though there are several reports on the ethnomedicinal use of this plant extract in stomach ulcers, experimental-based data is unavailable. The drive for carrying out this research was to obtain data on the possible ameliorative effect of the whole plant extract of Dissotis rotundifolia (DRE) in gastric ulcerations induced by ethanol in Sprague Dawley (SD) rats. SD rats were pretreated with 100, 300, and 500 mg/kg of DRE for 14 days after which an ulcerogen-ethanol was administered. Gross examinations of the stomach lining and histological analysis of gastric lesions were carried out coupled with an assessment of the antioxidant activity of gastric mucosa using MDA, GSH, CAT, and SOD as indicators. The data suggested a significant attenuation in gastric mucosal damage in DRE-pretreated ethanol-induced gastric ulcer reflected in the antioxidant status. There was also a reduction or absence of hemorrhage, edema, and leucocytes infiltration in DRE-treated groups compared to the negative control group. DRE conserved glutathione (GSH) levels, reduced malondialdehyde (MDA) levels, and enhanced catalase (CAT) and superoxide dismutase (SOD) enzyme levels. The present study shows that DRE possess protective effects against ethanol-induced ulcer damage in the stomach of rats, which could be attributed to its antioxidant activity.

Selenium Nanoparticles-Embedded Chitosan Microspheres and Their Effects Upon Alcohol-Induced Gastric Mucosal Injury in Rats: Rapid Preparation, Oral Delivery, and Gastroprotective Potential of Selenium Nanoparticles.

BackgroundSelenium (Se) is an indispensable trace element required for animals and human beings, whereas Se-deficiency can accelerate the development of acute gastric injury induced by over-consumption of alcohol. Selenium nanoparticles (SeNPs), as a special Se-supplement with favorable properties and unique bioactivities, are expected to play a passive role in gastroprotection. To the best of our knowledge, the gastroprotective potential of SeNPs is unknown and also, a rapid preparation of orally stable SeNPs available for prospective commercial application in the clinic is needed. Thus, SeNPs-embedded chitosan microspheres (SeNPs-CM) were developed to deliver SeNPs, and their gastroprotective potential was evaluated.ResultsHerein, a rapid, eco-friendly and economic preparation process, composed of synthesis of SeNPs decorated by chitosan (CS), purification of CS-SeNPs by ultra-filtration (UF) and spray-drying of the purified CS-SeNPs, was introduced to prepare SeNPs-CM. The uniformly distributed SeNPs with a nanosize range of 60 nm were loaded into CS-microspheres, and they could be released from the microspheres in gastric conditions. In addition, SeNPs-CM were safer than selenite in terms of Se dose, with a LD50 of around 8-fold of that of selenite, and it could efficiently enhance the Se retention in Se-deficient Wistar rats. Furthermore, SeNPs-CM pre-treatment might significantly attenuate the ethanol-induced gastric mucosal damage, based on histological evaluation. It might be partly attributed to the systematic antioxidant activities of SeNPs-CM, reflected by the reduction in lipid peroxidation, the augmentation in antioxidant enzymatic activity as well as decreasing aggressive nitric oxides (NO).ConclusionSeNPs-CM could be taken into consideration as a prospective Se-supplement for the oral delivery of SeNPs, with prominent gastroprotective effect against ethanol-induced mucosal injury.

Protective effects of total flavonoids from Alpinia officinarum rhizoma against ethanol-induced gastric ulcer in vivo and in vitro

Context Alpinia officinarum Hance (Zingiberaceae) is traditionally used to treat inflammation, pain, colds and digestive diseases. Objective To investigate the potential protective mechanism of total flavonoids from the rhizomes of A. officinarum (F-AOH) in ethanol-induced acute gastric in vivo and in vitro. Materials and methods In vivo: Gastric damage was induced in BALB/c mice by administering ethanol (10 mL/kg) after oral treatment with F-AOH at 126.8, 63.4 and 31.7 mg/kg or ranitidine (Ran) at 100 mg/kg (1 week of continuous gavage). In vitro: Gastric mucosal epithelial cells (GES-1) were incubated with F-AOH (8, 4 and 2 μg/mL) for 16 h and treated with 7% ethanol for 4 h. The extent of gastric damage was assessed histopathologically, and the expression of NF-κB, COX-2, TNF-α, iNOS and IL-1β was quantified by Western blot analysis. In addition, proinflammatory mediators and concentrations of motilin (MTL) and gastrin (GAS) were measured by ELISA test. Results F-AOH effectively reduced the ulcer index (from 23.4 ± 4.28 to 8.32 ± 1.5) and reduced release of inflammatory mediators (IL-1β, IL-6, TNF-α and PGE2), increased the content of nitric oxide and improved GAS and MTL secretion. The 50% inhibitory concentration (IC50) of F-AOH on cell damage was 17 μg/mL. F-AOH increased ethanol-induced cell survival (from 47 to 85%) and inhibited the expression of NF-κB, COX-2, TNF-α, IL-1β and iNOS proteins. Conclusions F-AOH inhibits ethanol-induced gastric mucosal damage, provides a theoretical basis for galangal in the treatment of other causes of GU, and promotes the application of galanga in the treatment of GU.

Evaluation of Antiulcer Activity of Lawsonia inermis and Murraya koenigii Seed Extract in Ethanol-induced Gastric Mucosal Damage in Rats

Evaluation of Antiulcer Activity of Lawsonia inermis and Murraya koenigii Seed Extract in Ethanol-induced Gastric Mucosal Damage in Rats

Ethnopharmacological Inspections of Organic Extract of Oroxylum indicum in Rat Models: A Promising Natural Gift.

The stem bark of Oroxylum indicum (O. indicum) was aimed at testing for anti-inflammatory, antiulcerative, antihyperglycemic, and antidyslipidemic activities. Liver enzyme concentration (SGPT, SGOT) had also been assessed. After being extracted in organic solvent, 3 distinct doses, 100, 200, and 400 mg/kg b.w. (p.o.), were used. For edema formation 0.1 ml carrageenan at a dose of 1% w/v was injected into paw of left hind. It showed a fall of edemas 37.50%, 48.34%, and 55.83% while used doses were 100, 200, and 400 mg/kg b.w. (p.o.) individually. The EtOH extract of O. indicum (50%) and its fractions PET, CLF, EtOAc, and nBUT were studied against ethanol-induced gastric mucosal damage. Only PET and n-BuOH exhibited the highest percentage of protection and were 96% and 99%, respectively, persuaded by ethanol. In OGTT glibenclamide revealed reduction of glucose level to 7.55 ± 0.22 mmol/L from 10.57 ± 0.32 mmol/L after 30 minutes. Antihyperglycemic activities were assessed for 8- and 12-week duration in diabetic rats. Glibenclamide reduced glucose level from 33.50±0.31 to 7.90±0.19 mmol/L in 12 weeks. In 12 and 8 weeks, combination therapy lowered blood glucose level to a normal extent by 79% and 61% individually. In antidyslipidemic activities after 12-week treatment, it revealed simvastatin; MEOI (400 mg/kg b.w.) and combination of both reduced TC level by 44%, 28%, and 48% consequently followed by TG and LDL. In 8-week treatment, HDL levels were increased by 34%, 13%, and 36%, and in 12 weeks increased by 36%, 8%, and 38% consequently. Liver enzyme concentration after 12 weeks of treatment with glibenclamide, 400 mg/kg b.w. (p.o.) of MEOI and combination of both, exhibited the fact that concentration of SGPT showed downturn by 43.23%, 8.01%, and 54.86% and SGOT by 42.40%, 5.31%, and 44.85%. This study remarked that O. indicum has anti-inflammatory, antiulcer, antidiabetic, and antidyslipidemic potentials but has no ameliorative effect on liver enzyme.

Protective Effects of Dioscorea batatas Flesh and Peel Extracts against Ethanol-Induced Gastric Ulcer in Mice.

Gastric ulcer is a major digestive disorder and provoked by multifactorial etiologies, including excessive alcohol consumption. In this study, we examined the gastroprotective effect of aqueous and ethanolic extracts of Dioscorea batatas Decne (DBD; commonly called Chinese yam) flesh or peel against acidified ethanol-induced acute gastric damage in mice. Our findings demonstrated that oral supplementation of aqueous or ethanolic extracts of DBD flesh or peel before ulcer induction was significantly effective in macroscopically and histologically alleviating ethanol-induced pathological lesions in gastric mucosa, decreasing the plasma levels of inflammatory mediators, such as nitric oxide and interleukin-6, attenuating the gastric expression of cyclooxygenase-2, and increasing the gastric content of prostaglandin E2. In particular, pretreatment with the flesh extract prepared in 60% ethanol prominently decreased the expression of biomarkers of oxidative stress, including the plasma levels of 8-hydroxy-2-guanosine and malondialdehyde, and restored heme oxygenase-1 expression and superoxide dismutase activity in the stomach. Overall, these findings suggest that the oral supplementation with DBD extract, especially flesh ethanol extract, prior to excessive alcohol consumption, may exert a protective effect against ethanol-induced gastric mucosal damage in vivo, presumably through the activation of the antioxidant system and suppression of the inflammatory response.

Effects of intracerebroventricularly injected glucagon-like peptide-2 on ethanol-induced gastric mucosal damage in rats

ABSTRACTPurpose: The present study aims to investigate the effects of intracerebroventricularly (i.c.v.)-injected glucagon-like peptide-2 (GLP-2) on ethanol-induced gastric mucosal damage and to reveal the mechanisms involved in this effect.Materials and Methods: Rats received absolute ethanol orally via an orogastric tube 30 minutes after GLP-2 (1–200 ng/10 µl; i.c.v.) or saline (10 µl) injections. They were decapitated 1 hour later, their stomachs were removed, and the gastric mucosal damage was scored.Results: A total of 100 ng GLP-2 inhibited the gastric mucosal damage by 67%. This effect was abolished by the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37) (10 µg/kg; s.c.), but was not affected by either the nitric oxide (NO) synthase inhibitor L-NAME (30 mg/kg; s.c.) or the cyclooxygenase inhibitor indomethacin (5 mg/kg; i.p.). The most effective gastroprotective dose of GLP-2 (100 ng/10 µl; i.c.v.), but not the higher doses (150 or 200 ng/10 µl; i.c.v.) prevented the decrease in gastric mucosal blood flow caused by ethanol.In conclusion, i.c.v. GLP-2 protects against ethanol-induced gastric mucosal damage and this effect is mediated by CGRP receptor activation and gastric mucosal blood flow, but not by NO or prostaglandins.

Protective effect of Pu-erh tea extracts against ethanol-induced gastric mucosal damage in rats.

Pu-erh tea has become a focus of research due to its reported biological activities, including anti-oxidation, anti-inflammation and anti-immunosenescence. The present study was performed to evaluate the potential gastroprotective function of Pu-erh tea extracts against ethanol-induced gastric mucosal damage in rats. Sprague Dawley rats were randomly divided into seven groups: A normal control, a model control, a cimetidine (0.08 g/kg) group, three Pu-erh tea extracts groups (low, moderate and high-dose; 0.50, 1.00 and 1.50 g/kg, respectively, and a green tea powder (1.00 g/kg) group. The normal and model groups were pre-treated with distilled water while the other groups were respectively administered cimetidine, Pu-erh tea extracts and green tea powder for 14 days. Then, absolute ethanol was orally administered to the rats of all groups excluding the normal controls. The effects of the pretreatments on gastric mucosal injury were evaluated by gross assessment of gastric lesions, examination of histopathology and determination of myeloperoxidase (MPO) activity and asymmetric arginine (ADMA) concentration in gastric mucosal homogenate. Pre-treatment with cimetidine or Pu-erh tea extracts markedly suppressed the formation of ethanol-induced gastric lesions. Furthermore, clear decreases in MPO activity and ADMA concentration in the gastric mucosal homogenate were observed following pretreatment with cimetidine or Pu-erh tea extracts. The anti-gastric ulcer activity of green tea was less than that of Pu-erh tea. Overall, these effects of Pu-erh tea extracts may be due to potential functions in protecting the gastric mucus layer and suppressing inflammation.