Ethanol-induced Acute Gastric Injury Research Articles

Aibika Flower Flavonoid Extract Exhibits Antiulcer Activity in a Murine Model of Ethanol-Induced Acute Gastric Injury.

Aibika (Abelmoschus manihot (L.) Medic) is a garden vegetable whose flower has been shown to have various bioactivities. This study investigated the protective effect of aibika flower flavonoid extract (AFF) on ethanol-induced gastric injury in mice. The experimental results showed that pre-feeding 125 and 250 mg AFF/kg BW for 1 week significantly reduced the gastric injury area in the negative control group from 19.2% to 6.7% and 0.6%, respectively. The results of the pathological sections staining also showed that AFF had a protective ability against alcohol-induced injury of gastric tissue and liver tissue. When the mice were exposed to high concentrations of ethanol, AFF pretreatment significantly upregulated the expression of antioxidant enzymes. The pretreatment also promoted the production of the intracellular antioxidant, reduced glutathione, in both gastric tissue and serum. On the contrary, AFF delayed the lipid peroxidation process, which, in turn, reduced the damage to the gastric mucosa. When acute inflammation was induced by ethanol stimulation, AFF significantly downregulated the proinflammatory cytokines and mediators such as TNF-α, IL-1β, IL-6, NF-κB, COX-2, and iNOS. Furthermore, AFF pretreatment greatly promoted the production of healing factors, such as matrix metalloproteinase (MMP)-2, MMP-7, and MMP-9, in the gastric tissue. In addition, AFF significantly reduced gastric cell apoptosis induced by ethanol stimulation. These results demonstrate that AFF has a good protective effect on alcohol-induced gastric ulcer and has the potential to be used in gastrointestinal health care.

Albizzia chinensis (Osbeck) Merr extract YS ameliorates ethanol-induced acute gastric ulcer injury in rats by regulating NRF2 signaling pathway.

Around the world, there is a high incidence of gastric ulcers. YS, an extract from the Chinese herb Albizzia chinensis (Osbeck) Merr, has potential therapeutic applications for gastrointestinal diseases. Here we elucidated the protective effect and underlying mechanism of action of YS on gastric ulcer in rats injured by ethanol. The ethanol-induced gastric ulcer rat model was used to assess the protective effect of YS. A pathological examination of gastric tissue was performed by H&E staining. GES-1 cells damaged by hydrogen peroxide were used to simulate oxidative damage in gastric mucosal epithelial cells. Endogenous NRF2 was knocked down using small interfering RNA. Immunoprecipitation was used to detect ubiquitination of NRF2. Co-immunoprecipitation was used to detect the NRF2-Keap1 interaction. YS (10 and 30 mg/kg, i.g.) significantly reduced the ulcer index, decreased MDA level, and increased SOD and GSH levels in gastric tissues damaged by ethanol. YS promoted NRF2 translocation from cytoplasm to nucleus and enhanced the NQO1 and HO-1 expression levels in injured rat gastric tissue. In addition, YS regulated NQO1 and HO-1 via NRF2 in H2O2-induced oxidative injured GES-1 cells. Further studies on the underlying mechanism indicated that YS reduced the interaction between NRF2 and Keap1 and decreased ubiquitylation of NRF2, thereby increasing its stability and expression of downstream factors. NRF2 knockdown abolished the effect of YS on MDA and SOD in GES-1 cells treated with H2O2. YS reduced the NRF2-Keap1 interaction, promoting NRF2 translocation into the nucleus, which increasing the transcription and translation of NQO1 and HO-1 and improved the antioxidant capacity of rat stomach.

Construction of diallyltrisulfide nanoparticles for alleviation of ethanol-induced acute gastric injury

Gastric ulcer, a significant health issue characterized by the degradation of the gastric mucosa, often arises from excessive gastric acid secretion and poses a challenge in current medical treatments due to the limited efficacy and side effects of first-line drugs. Addressing this, our study develops a novel therapeutic strategy leveraging gas therapy, specifically targeting the release of hydrogen sulfide (H2S) in the treatment of gastric ulcers. We successfully developed a composite nanoparticle, named BSA·SH-DATS, through a two-step process. Initially, bovine serum albumin (BSA) was sulfhydrated to generate BSA·SH nanoparticles via a mercaptosylation method. Subsequently, these nanoparticles were further functionalized by incorporating diallyltrisulfide (DATS) through a precise Michael addition reaction. This sequential modification resulted in the creation of BSA·SH-DATS nanoparticles. Our comprehensive in vitro and in vivo investigations demonstrate that these nanoparticles possess an exceptional ability for site-specific action on gastric mucosal cells under the controlled release of H2S in response to endogenous glutathione (GSH), markedly diminishing the production of pro-inflammatory cytokines, thereby alleviating inflammation and apoptosis. Moreover, the BSA·SH-DATS nanoparticles effectively regulate critical inflammatory proteins, including NF-κB and Caspase-3. Our study underscores their potential as a transformative approach for gastric ulcer treatment.

Construction of Magnolol Nanoparticles for Alleviation of Ethanol-Induced Acute Gastric Injury.

Ethanol (EtOH) has been identified as a potential pathogenic factor in gastric ulcer development primarily due to its association with gastric injury and excessive production of reactive oxygen species. Magnolol (Mag), the principal active compound in Magnolia officinalis extract, is well studied for its notable anti-inflammatory and antioxidant properties. However, its limited solubility, propensity for agglomeration, and low absorption and utilization rates significantly restrict its therapeutic use. This study aims to overcome these challenges by developing a Mag nanoparticle system targeting the treatment and prevention of EtOH-induced gastric ulcers in mice. Utilizing a click chemistry approach, we successfully synthesized this system by reacting thiolated bovine serum albumin (BSA·SH) with Mag. The in vitro analysis revealed effective uptake of the BSA·SH-Mag nanoparticle system by human gastric epithelial cells (GES-1), showcasing its antioxidant and anti-inflammatory capabilities. Additionally, BSA·SH-Mag exhibited gradual disintegration and release in simulated gastric fluid, resulting in a notable reduction of oxidative stress in gastric tissues and mucosal tissue repair and effectively reducing inflammatory expression. Furthermore, BSA·SH-Mag attenuated EtOH-induced gastric inflammation by decreasing the level of NOX4 protein expression and augmenting the level of Nrf2 protein expression. In conclusion, our findings indicate that BSA·SH-Mag represents a promising candidate as an oral therapeutic for gastric ulcer treatment.

Multifunctional gallic acid self-assembled hydrogel for alleviation of ethanol-induced acute gastric injury

Ethanol-induced acute gastric injury is a prevalent type of digestive tract ulcer, yet conventional treatments strategies frequently encounter several limitations, such as poor bioavailability, degradation of enzymes and adverse side effects. Gallic acid (GA), a natural compound extracted from dogwood, has demonstrated potential protective effects in mitigating acute gastric injury. However, its poor stability and limited bioavailability have restricted applications in vivo. To address these issues, we report a hydrogel constructed only by gallic acid with high bioavailability for alleviation of gastric injury. Molecular dynamic simulation studies revealed that the self-assembly of GA into hydrogel was predominantly attributed to π-π and hydrogen bonds. After assembling, the GA hydrogel exhibits superior anti-oxidative stress, anti-apoptosis and anti-inflammatory properties compared with free GA. As anticipated, in vitro experiments demonstrated that GA hydrogel possessed the remarkable ability to promote the proliferation of GES-1 cells, and alleviates apoptosis and inflammation caused by ethanol. Subsequent in vivo investigation further confirmed that GA hydrogel significantly alleviated ethanol-triggered acute gastric injury. Mechanistically, GA hydrogel treatment enhanced the antioxidant capacity, reduced oxidative stress while simultaneously suppressing the secretion of pro-inflammatory cytokines and reduced the production of pro-apoptotic proteins during the process of gastric injury. Our finding suggest that this multifunctional GA hydrogel is a promising candidate for gastric injury, particularly in cases of ethanol-induced acute gastric injury.

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

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

Gastroprotective Effects of Ganoderma lucidum Polysaccharides with Different Molecular Weights on Ethanol-Induced Acute Gastric Injury in Rats.

Ganoderma lucidum is known as a medicine food homology that can ameliorate gastrointestinal diseases. To evaluate the gastroprotective effects on different Ganoderma lucidum polysaccharides (GLPs), GLP was separated into three parts with different molecular weights using 100 kDa, 10 kDa, and 1 kDa membranes. The mitigation effects of different GLPs on ethanol-induced acute gastric injury were observed in rats. After pretreatment with different GLPs, especially GLP above 10 kDa, the symptoms of gastric mucosal congestion and bleeding were improved; serum myeloperoxidase, inflammatory factor, and histamine were decreased; and antioxidant activity and defense factors (NO and EGF) were increased. Results showed that GLP with different molecular weights had a dose-dependent effect in alleviating alcohol-induced gastric injury. The underlying mechanism might be related to regulating anti-oxidation, promoting the release of related defense factors, reducing inflammatory factors, and reducing the level of histamine in serum. The current work indicated that GLPs above 10 kDa could be applied as natural resources for producing new functional foods to prevent gastric injury induced by ethanol.

Preparation of deer oil powder and its effect on acute gastric mucosal injury in rats.

In this paper, deer oil was used as a raw material to prepare deer oil powder by microencapsulation technology to study the potential protective activity of deer oil powder on ethanol-induced acute gastric mucosal injury in rats. The results show that the best process for preparing deer oil powder is: the solids account for 25% of the system content, the wall material Whey Milk Protein Isolate-Maltodextrin ratio is 1:5, the Sodium Stearyl Lactate-Glycerides of Monostearate and Distearate compound emulsifier content is 0.8%, the ratio is 1:1, and the deer oil accounts for 30% of the solid content, and the spray drying inlet temperature is 180°C. Deer oil powder can reduce total stomach injury, gastric mucosal congestion area, and injury score index. Without affecting the blood lipid level, it can reduce the content of Myeloperoxidase, enhance the activity of Superoxide Dismutase and Glutathione Peroxidase, and has good antioxidant activity. Enhance the expression of defense factors Estradiol, Epidermal Growth Factor, and Somatostatin. At the same time, it reduces the levels of Interleukin-1β and Interleukin-6 pro-inflammatory cytokines in gastric tissue and enhances the expression of anti-inflammatory factors Interleukin-4 and Interleukin-10. These results indicate that the gastric protection mechanism of deer oil powder may be related to the enhancement of mucosal defense factors, inhibition of inflammation, and oxidative stress. PRACTICAL APPLICATIONS: This study screened the optimal formula for preparing microencapsulated deer oil powder and proved for the first time that deer oil powder has a strong gastroprotective effect on ethanol-induced acute gastric injury in rats. The gastric protective mechanism of deer oil powder is mainly to reduce oxidative stress, inflammatory cytokine accumulation and to increase the content of defense factors. Therefore, deer oil powder can be used as a new source of gastric treatment drugs.

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

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

Gastroprotective Effect of Myricetin on Ethanol-Induced Acute Gastric Injury in Rats.

The flavonoid myricetin is abundant in vegetables and has various bioactive properties, including anti-inflammatory and antioxidative activities. In the present study, we explored the effects of myricetin on alcohol-induced gastric ulcer in a rat model. To induce gastric ulcer, absolute ethanol (5 mL/kg body weight) was orally administrated to each rat. The positive control and myricetin-treated groups were given oral doses of omeprazole (20 mg/kg) or myricetin (12 mg/kg), respectively, 1 hour prior to the administration of absolute alcohol. We found that pretreatment with myricetin significantly decreased alcohol-induced gastric ulcer, hemorrhage, hyperemia, and epithelial cell loss in the gastric mucosa. Myricetin pretreatment reduced the level of malondialdehyde (MDA) and increased that of total glutathione (GSSG/GSH) and superoxide dismutase (SOD) in gastric tissues. In addition, it elevated the expression levels of cyclooxygenase-1 (COX-1) and prostaglandin E2 (PGE2) and decreased the phosphorylation of nuclear factor kappa B (NF-κB). Together, these results indicate that myricetin effectively inhibits ethanol-induced acute gastric injury by preventing oxidative damage, stimulating PGE2 production, and inhibiting NF-κB activation. We suggest that myricetin may be an alternative treatment for gastric injury caused by alcohol intake.

Comparative study of raw and processed Vladimiriae Radix on pharmacokinetic and anti-acute gastritis effect through anti-oxidation and anti-inflammation

BackgroundVladimiriae Radix (VR) is the dry root of Vladimiria souliei (Franch.) Ling or Vladimiria souliei (Franch.) Ling var. cinerea Ling. Costunolide (CO) and dehydrocostus lactone (DE) are the two most effective active ingredients of VR. Raw Vladimiriae radix (rVR) and processed Vladimiriae radix (pVR) are the two most common forms. They have been used for hundreds of years to treat gastritis, gastric ulcer and gastrointestinal pain, but their protective effects on gastric mucosa have been widely considered to be different, and the mechanism is not clear. PurposeA comparative study of in vivo process and efficacy difference of raw and processed Vladimiriae Radix was carried out to explore the treatment mechanism and to provide reference for the rationality of clinical usage. MethodsIn this study, multi-batch rVR and pVR were used to establish the characteristic chromatograms through high performance liquid chromatography (HPLC) to control the qualities of their extracts. A rapid and accurate ultra-high performance liquid chromatography - mass spectrometry (UPLC-MS) method was established and verified, and the concentrations of CO and DE in plasma of rats after oral administration were determined to analyze the pharmacokinetics. The anti-inflammatory and antioxidant activities of ethanol-induced acute gastric mucosa injury (AGMI) in rats were quantitatively analyzed by ELISA and Westernblot methods. ResultsCharacteristic chromatograms study showed that there were 9 common characteristic peaks between the chromatograms of rVR and pVR, and there was a high level (> 0.90) of the similarity between batches (only one batch less than 0.90). The increased levels of Tmax, T1/2 and MRT were found in rats treated with the pVR. Animal model studies indicated that both the two forms of VR could relieve AGMI, but pVR could more effectively reduce the content of ethanol in blood and lower the levels of TNF-α, IL-6, IL-1β, NO, iNOS and MDA, and increase the level of SOD. Results of Westernblot proved that pVR also could inhibit the expression of NF-κB p65, IκBα and up-regulate the expression of HO-1 and NRF2 more operatively to protect gastric mucosa through anti-inflammatory and antioxidant stress mechanisms. ConclusionCompared with rVR, pVR has an accelerated absorption in vivo and its effect time was prolonged, and the observed improvement of anti-AGMI effect was achieved through anti-oxidation and anti-inflammation regulation.

Effect of heat-killed Enterococcus faecalis EF-2001 on ethanol-induced acute gastric injury in mice: Protective effect of EF-2001 on acute gastric ulcer.

Enterococcus faecalis is a facultative anaerobic gram-positive commensal bacterium common in the gastrointestinal tract of animals and humans. This study aimed to investigate the protective effects of heat-killed E. faecalis EF-2001 (EF-2001) on acute gastric ulcer using a murine model of ethanol (EtOH)-induced acute gastric injury. EF-2001 (20, 40, and 80 mg/kg/day) was administered by oral gavage for 5 days before EtOH treatment (10 mL/kg body weight). EF-2001 effectively attenuated EtOH-induced gastric mucosal injury with reduced gastric mucosal ulcer and histological damage score. Pretreatment of EF-2001 markedly suppressed the phosphorylation of mitogen-activated protein kinases (MAPKs; ERK1/2, JNK, and p38MAPK). In addition, EF-2001 significantly inhibited phosphorylation of nuclear factor kappa B (NF-κB) and subsequently suppressed the upregulation of inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 in gastric tissues. Taken together, these results suggest that EF-2001 exerts a gastroprotective effect against acute gastric injury, and the underlying mechanism might be associated with the suppression of MAPKs and NF-κB signaling and consequent reduction of pro-inflammatory mediators or cytokines.

Protective effects of genipin on ethanol-induced acute gastric injury in mice by inhibiting NLRP3 inflammasome activation

Genipin has been shown to exert anti-inflammatory effects, but its mechanism in protecting the ethanol-induced acute gastric injuries remains largely unclear. The present study aimed to investigate the effects of genipin on ethanol-induced acute gastric injuries in mice. After intragastrical administration of genipin for 7 consecutive days, acute gastric injuries were induced in the mice by ethanol treatment for 1 h. The expression levels of MDA, MPO, SOD, CAT, and NO in gastric tissues, and the levels of IL-6, TNF-α, MTL, SP, VIP and SS in serum samples were measured by ELISA. In addition, Western blotting was used to determine the expression levels of proteins involved in NLRP3 signaling pathway. The findings revealed that oral administration of genipin significantly ameliorated the pathological injury of gastric mucosa induced by ethanol, decreased the oxidative stress induced by ethanol and suppressed the expression levels of in-flammatory cytokines in gastric tissues and serum samples. In addition, it was observed that oral administration of genipin could remarkably inhibit the expression levels of related proteins in the NLRP3 signaling pathway. In conclusion, these results suggest that genipin may exhibit protective roles in ethanol-induced gastric mucosal injuries by activating antioxidant system and attenuating inflammatory reaction.

The caspase-1 inhibitor AC-YVAD-CMK attenuates acute gastric injury in mice: involvement of silencing NLRP3 inflammasome activities.

This study evaluated the protective effects of inhibiting caspase-1 activity or gastric acid secretion on acute gastric injury in mice. AC-YVAD-CMK, omeprazole, or vehicle were administered to mice before cold-restraint stress- or ethanol-induced gastric injury. Survival rates and histological evidence of gastric injury of mice pretreated with AC-YVAD-CMK or omeprazole, and exposed to cold-restraint stress, improved significantly relative to the vehicle group. The increased levels of tumour necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-18 following cold-stress injury were decreased by AC-YVAD-CMK, but not omeprazole, pretreatment. The increased expression of CD68 in gastric tissues was inhibited significantly by AC-YVAD-CMK pretreatment. Inhibiting caspase-1 activity in the NLRP3 inflammasome decreased gastric cell apoptosis, and the expression of Bax and cleaved caspase-3. AC-YVAD-CMK pretreatment significantly inhibited cold-restraint stress-induced increases in the expression of phosphorylated IκB-alpha and P38. General anatomy and histological results showed the protective effect of AC-YVAD-CMK on ethanol-induced acute gastric injury. Overall, our results showed that the caspase-1 inhibitor AC-YVAD-CMK protected against acute gastric injury in mice by affecting the NLRP3 inflammasome and attenuating inflammatory processes and apoptosis. This was similar to the mechanism associated with NF-κB and P38 mitogen-activated protein kinase signalling pathways.

Protective Effects of Manassantin A against Ethanol-Induced Gastric Injury in Rats.

Manassantin A, a neolignan isolated from Saururus chinensis, is a major phytochemical compound that has various biological activities, including anti-inflammatory, neuroleptic, and human acyl-CoA : cholesterol acyltransferase (ACAT) inhibitory activities. In this study, we investigated the protective effects of manassantin A against ethanol-induced acute gastric injury in rats. Gastric injury was induced by intragastric administration of 5 mL/kg body weight of absolute ethanol to each rat. The positive control group and the manassantin A group were given oral doses of omeprazole (20 mg/kg) or manassantin A (15 mg/kg), respectively, 1 h prior to the administration of absolute ethanol. Our examinations revealed that manassantin A pretreatment reduced ethanol-induced hemorrhage, hyperemia, and epithelial cell loss in the gastric mucosa. Manassantin A pretreatment also attenuated the increased lipid peroxidation associated with ethanol-induced acute gastric lesions, increased the mucosal glutathione (GSH) content, and enhanced the activities of antioxidant enzymes. The levels of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β were clearly decreased in the manassantin A-pretreated group. In addition, manassantin A pretreatment enhanced the levels of cyclooxygenase (COX)-1, COX-2, and prostaglandin E2 (PGE2) and reduced the inducible nitric oxide synthase (iNOS) overproduction and nuclear factor kappa B (NF-κB) phosphorylation. Collectively, these results indicate that manassantin A protects the gastric mucosa from ethanol-induced acute gastric injury, and suggest that these protective effects might be associated with COX/PGE2 stimulation, inhibition of iNOS production and NF-κB activation, and improvements in the antioxidant and anti-inflammatory status.

Banhabaekchulchunma-tang, a traditional herbal formula attenuates absolute ethanol-induced gastric injury by enhancing the antioxidant status

BackgroundBanhabaekchulchunma-tang (hange-byakujutsu-tenma-to in Japanese and banxia-baizhu-tianma-tang in Chinese) is a mixture of fourteen herbs. It is used traditionally for the treatment of anemia, anorexia, general weakness, and female infertility in China, Japan, and Korea. In this study, we investigated the protective effects of a Banhabaekchulchunma-tang water extract (BCT) against ethanol-induced acute gastric injury in rats.MethodsGastric injury was induced by intragastric administration of 5 mL/kg body weight of absolute ethanol to each rat. The positive control group and the BCT group were given oral doses of omeprazole (50 mg/kg) or BCT (400 mg/kg), respectively, 2 h prior to the administration of absolute ethanol. The stomach of each animal was excised and examined for gastric mucosal lesions. To confirm the protective effects of BCT, we evaluated the degree of lipid peroxidation, the level of reduced glutathione (GSH), and the activities of the antioxidant enzymes catalase, glutathione-S-transferase, glutathione peroxidase, and glutathione reductase in the stomach. In addition, we conducted an acute toxicity study to evaluate the safety of BCT according to OECD guideline.ResultsBCT reduced ethanol-induced hemorrhage, hyperemia, and loss of epithelial cell in the gastric mucosa. BCT reduced the increased lipid peroxidation associated with ethanol-induced acute gastric lesions, and increased the mucosal GSH content and the activities of antioxidant enzymes. In addition, BCT did not cause any adverse effects at up to 5000 mg/kg.ConclusionsThese results indicate that BCT protects the gastric mucosa against ethanol-induced gastric injury by increasing the antioxidant status. We suggest that BCT could be developed as an effective drug for the treatment of gastric injury caused by alcohol intake.

Gastroprotective effects of Leejung-tang, an oriental traditional herbal formula, on ethanol-induced acute gastric injury in rats

Leejung-tang (LJT, Rechu-to in Japanese and Lizhong-tang in Chinese) is an oriental traditional traditional herbal formula. LJT has been used for treatment of gastrointestinal disorders in Korea, Japan, and China for a long time. In present study, we investigated the protective effects of LJT against absolute ethanol induced gastric injuries. Rats in the control group were given PBS orally (5 mL/kg body weight) as the vehicle, and the absolute-ethanol group (EtOH group) received absolute ethanol (5 mL/kg body weight) by oral gavage. Rats in the positive control group were given omeprazole orally (50 mg/kg body weight) 2 h prior to the administration of absolute ethanol. The treatment groups received LJT (400 mg/kg body weight) 2 h prior to absolute ethanol administration. All rats were sacrificed 1 h after receiving the ethanol treatment. The stomach was excised for macroscopic examination and biochemical analysis. The administration of LJT protected gastric mucosa against ethanol-induced acute gastric injury, including hemorrhage and hyperemia. LJT reduced the increase in lipid peroxidation in ethanol-induced acute gastric lesions. LJT increased GSH content and activities of the antioxidant enzymes, catalase, glutathione-S-transferase, glutathione reductase, glutathione peroxidase, and superoxide dismutase. These results indicate that LJT protects gastric mucosa against ethanol-induced acute gastric injury by increasing their antioxidant content. We suggest that LJT can be developed as an effective drug for the treatment of acute gastric injury.

Musashi-1 post-transcriptionally enhances phosphotyrosine-binding domain-containing m-Numb protein expression in regenerating gastric mucosa.

ObjectiveUpregulation of the RNA-binding protein Musashi-1 (Msi1) has been shown to occur in rat gastric corpus mucosa after ethanol-induced mucosal injury. However, there is no direct evidence linking Msi1 with gastric regeneration. We examined the process of tissue repair after acute gastric mucosal injury with Msi1-knock-out (KO) mice to clarify the role of Msi1 and Msi1-dependent regulation of m-Numb expression in regenerating gastric mucosa.MethodsAcute gastric injury was induced in Msi1-KO and wild-type ICR mice by administering absolute ethanol. Expression of the splicing variants of m-Numb mRNA and protein in the gastric mucosa were analyzed by quantitative RT-PCR and western blotting, respectively.ResultsWe demonstrated that phosphotyrosine-binding domain-containing m-Numb expression was significantly upregulated at both the mRNA and protein levels in wild-type mice at 3 h after ethanol-induced acute gastric injury. In contrast, in Msi1-KO mice, the m-Numb protein was expressed weakly, and was associated with delayed regeneration of the injured gastric mucosal epithelium. In the Msi1-KO mouse, the ratio of m-Numb mRNA to total m-Numb mRNA in the heavy polysome fractions was lower than that in the wild-type mouse. Further, we showed that m-Numb-enhancement in gastric mucous cells induced the expression of prostate stem cell antigen and metallothionein-2. Under the m-Numb enhancing condition, the gastric cells exhibited enhanced cell proliferation and were significantly more resistant to H2O2-induced cell death than control cells.ConclusionsMsi1-dependent post-transcriptional enhancement of m-Numb is crucial in gastric epithelial regeneration.

Protective effect of Bojungikki-tang, a traditional herbal formula, against alcohol-induced gastric injury in rats

Ethnopharmacological evidenceOxidative stress plays an important role in the pathogenesis of ethanol-induced acute gastric mucosal injury. Bojungikki-tang (Hochuekkito in Japanese, Bu-zhong-yi-qi-tang in Chinese) is a traditional herbal formula used in Korea, Japan, and China to treat allergic diseases and gastrointestinal disorders. However, the mechanism responsible for its actions has not been investigated experimentally. Aim of the studyThe aims of this study were to investigate whether Bojungikki-tang water extract (BJITE) has protective effects against ethanol-induced acute gastric injury in rats and to perform an acute toxicity study to evaluate its safety. Materials and methodsIn this rat model, gastric mucosal injury was imposed by oral administration of 5mL/kg body weight of absolute ethanol. BJITE at one of two doses (200 or 400mg/kg body weight) was administered by gavage 2h before ethanol administration. Gastric tissues were collected and analyzed to assess the gastric injury index, and content or activity of catalase, superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), glutathione-S-transferase (GST), glutathione reductase (GR), and glutathione peroxidase (GPx). ResultsAcute administration of ethanol significantly increased the gastric injury index concomitantly with an increase in MDA and GSH content, and a decrease in the activities of catalase, GST, GR, GPx, and SOD. Pretreatment with 200 or 400mg/kg BJITE attenuated ethanol-induced gastric mucosal injury; this was accompanied by an increase in the content or activity of PGE2, catalase, GSH, GST, GR, GPx, and SOD, and a decrease in MDA content. In the acute toxicity study, no adverse effects of BJITE were observed at doses up to 2000mg/kg body weight. ConclusionThese results indicate that BJITE can partly protect the gastric mucosa from ethanol-induced acute gastric injury and suggest that these protective effects might be induced by increasing the antioxidant status. We suggest that BJITE can be developed as an effective drug for the treatment of acute gastric injury.

Yijin-tang, an oriental herbal formula reduces ethanol-induced acute gastric injury in rats

Protective effects of Yijin-tang extract (YTE) were investigated on ethanol-induced acute gastric injury. Simultaneous determination of six components, homogentisic aicd, liquiritin, hesperidin, neohesperidin, poncirin, and glycyrrhizin was performed in YTE by high performance liquid chromatography-photodiode. Acute gastric lesion was induced by oral administration of absolute ethanol (5 mL/kg). The positive control (omeprazole, 50 mg/kg) and YTE groups (200 and 400 mg/kg) were administered by oral gavage 2 h prior to ethanol treatment. The animals were sacrificed 1 h after receiving ethanol treatment. Acute toxicity study was performed to evaluate the safety of YTE. YTE protected gastric mucosa against ethanol-induced acute gastric injury including hemorrhage and hyperemia. YTE reduced the elevated lipid peroxidation of stomach and increased the activities of antioxidant enzyme. In the acute toxicity study, YTE did not cause any toxic effect at the dose level of 2000 mg/kg in rats. These results showed that YTE protects gastric mucosa from ethanolinduced acute gastric injury via increasing the antioxidant status. We suggest that YTE has a potential as a therapeutic agent for acute gastric injury.