Targeting TRPV1 signaling: Galangin improves ethanol-induced gastric mucosal injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Galangin, a bioactive compound extracted from Alpinia officinarum Hance (Zingiberaceae), a plant with significant ethnopharmacological importance, has been used for thousands of years as a spice, condiment, and medicinal agent for various conditions, including gastrointestinal disorders. Although there is evidence suggesting its potential to improve gastric ulcers, the molecular mechanisms underlying its anti-ulcer properties are not fully understood. OBJECTIVE: of the Study: This study aimed to investigate the effects of galangin on ethanol-induced acute gastric mucosal injury (AGMI) in mice and elucidate its molecular mechanisms. MATERIALS AND METHODS: Sixty BALB/c mice were randomly assigned into two main groups: a normal control group (n = 10) and an ethanol-induced group (n = 50). After establishing the AGMI model in mice using a combination of 40% ethanol and anhydrous ethanol, the ethanol-induced group was further subdivided into five subgroups (n = 10): an omeprazole control group (20 mg/kg), an untreated ethanol group, and three treatment groups receiving high-dose (50 mg/kg) or low-dose (25 mg/kg) galangin or capsazepine (CPZ, 2 mg/kg). The protective effects of galangin were evaluated through mucosal injury indices, hematoxylin and eosin staining, and quantification of inflammatory markers (IL-1ß, IL-6, IL-8, and TNF-α). Oxidative stress levels and matrix metalloproteinase activity were measured using specific assay kits. Molecular docking was conducted to assess the binding affinity of galangin to key proteins within the transient receptor potential vanilloid 1 (TRPV1) pathway. Real-time fluorescence quantitative PCR (qPCR) was used to determine mRNA expression levels of TRPV1, calmodulin (CaM), substance P (SP), and CGRP in gastric tissues. Protein expression levels of TRPV1, nerve growth factor (NGF), tropomyosin receptor kinase A (TRKA), transforming growth factor beta (TGF-ß), cyclooxygenase-2 (COX-2), and nuclear factor kappa B (NF-κB) were assessed through Western blot analysis. In cellular experiments, Culture of Human Gastric Epithelial Cells (GES-1) were treated with various concentrations of galangin after 7% ethanol induction. Cell proliferation, apoptosis, and migration were evaluated using Hoechst 33258 staining and transwell migration assays. TRPV1 protein expression was detected using immunofluorescence, and the expression levels of Bcl-2, BCL2-Associated X (BAX), and Caspase-3 were quantified by qPCR. Additionally, specific probe kits were used to measure intracellular calcium ions (Ca2+) and mitochondrial membrane potential. RESULTS: The findings indicate that galangin significantly improved mucosal pathology by reducing ulcer indices and inflammatory levels, while enhancing superoxide dismutase (SOD) activity and decreasing malondialdehyde (MDA) concentration. Galangin also reduced matrix metalloproteinase-2 (MMP-2), m metalloproteinase-9 (MMP-9) levels, promoting mucosal repair. At the cellular level, galangin decreased intracellular calcium ion concentration and mitigated the decline in mitochondrial membrane potential, enhance the restoration of mucosal cells, increased migration and proliferation, and reduced apoptosis. Molecularly, galangin demonstrated favorable binding to TRPV1, NGF, TRKA, TGF-ß, COX-2, and NF-κB, and reversed the elevated expression of these proteins. Additionally, galangin downregulated the mRNA expression of TRPV1, CaM, SP, CGRP, BAX, and Caspase-3 in gastric tissues/cells, while upregulating Bcl-2 mRNA expression. CONCLUSION: Galangin mitigates AGMI by inhibiting the overactivation of the TRPV1 pathway, thereby blocking aberrant signal transduction. This study suggests that galangin has therapeutic potential against ethanol-induced AGMI and may be a viable alternative for the treatment of alcohol-induced gastric mucosal injuries.

Gastroprotective Effect of Isoferulic Acid Derived from Foxtail Millet Bran against Ethanol-Induced Gastric Mucosal Injury by Enhancing GALNT2 Enzyme Activity.

Excessive alcohol consumption has led to the prevalence of gastrointestinal ailments. Alleviating gastric disorders attributed to alcohol-induced thinning of the mucus layer has centered on enhancing mucin secretion as a pivotal approach. In this study, foxtail millet bran polyphenol BPIS was divided into two components with MW < 200 D and MW > 200 D by molecular interception technology. Combined with MTT, cell morphology observation, and trypan blue staining, isoferulic acid (IFA) within the MW < 200 D fraction was determined as the effective constituent to mitigate ethanol-induced damage of gastric epithelial cells. Furthermore, a Wistar rat model with similar clinical features to alcohol-induced gastric mucosal injury was established. Then, gastric morphological observation, H&E staining, and assessments of changes in gastric hexosamine content and gastric wall binding mucus levels were carried out, and the results revealed that IFA (10 mg/Kg) significantly ameliorated alcohol-induced gastric mucosal damage. Finally, we applied techniques including Co-IP, molecular docking, and fluorescence spectroscopy and found that IFA inhibited the alcohol-induced downregulation of N-acetylgalactosamintransferase 2 (GALNT2) activity related to mucus synthesis through direct interaction with GALNT2 in gastric epithelial cells, thus promoting mucin synthesis. Our study lays a foundation for whole grain dietary intervention tailored to individuals suffering from alcoholic gastric mucosal injury.

Cinnamaldehyde alleviates aspirin-induced gastric mucosal injury by regulating pi3k/akt pathway-mediated apoptosis, autophagy and ferroptosis.

BACKGROUND: Gastric mucosal injury is a chronic and progressive stomach disease that can be caused by nonsteroidal anti-inflammatory drugs (NSAIDs). Therefore, there is an urgent need to find safe and effective drugs to prevent gastric mucosal injury due to NSAIDs. Cinnamaldehyde (CA) is a bioactive compound extracted from the rhizome of cinnamon and has various pharmacological functions, including anti-inflammatory, analgesic, antiapoptotic, and antioxidant activities. However, the potential pharmacological effect of CA on gastric mucosal injury remains unknown. PURPOSE: The aim of this study was to investigate the protective effects of CA on aspirin-induced gastric mucosal injury and to explore its mechanism of action METHODS: The effect of CA on gastric mucosal injury was investigated in vitro and in vivo, in vitro mouse model of gastric mucosal injury induced by aspirin, in vitro model of GES-1 cell injury by aspirin and Erastin. The mechanism of action of CA was determined using Transcriptomics and bioinformatics. RESULTS: CA exerted its protective effects against gastric mucosal injury by modulating the downstream targets, including mTOR, GSK3ß, and NRF2, via the PI3K/AKT signaling pathway to inhibit autophagy, apoptosis, and ferroptosis in the gastric epithelial cells. Further cellular experiments confirmed that the PI3K/AKT pathway was a key target for CA against gastric mucosal injury. CONCLUSION: This study provides the first evidence of CA, an active compound in cinnamon, possessing therapeutic potential in preventing and treating gastric mucosal injury, with its mechanism involving the regulation of apoptosis, autophagy, and ferroptosis in gastric epithelial cells mediated by the PI3K/AKT signaling pathway.

The protective effects and potential mechanisms of fulvic acid against ethanol-induced gastric mucosal injury in mice.

Fulvic acid (FA) is a kind of natural organic acids extracted from lignite, which is the active ingredient in Wujin oral liquid, a proprietary Chinese medicine used to treat gastric and duodenal ulcers. However, our understanding of the mechanisms of FA remains limited. Currently, the protection of FA and its mechanism were explored using the ethanol-induced gastric mucosal injury mouse model. The histopathological examinations showed FAs at three doses effectively reduced gastric congestion, oedema caused by ethanol, and prevented gastric epithelial cell fall-off. When compared to the model group, FAs reduced IL-1ß and IL-6 levels in serum, as well as IL-1ß, IL-6, TNF-α, and COX-2 expression levels in tissue. Furthermore, FAs significantly inhibited p65, P38 MAPK, and Erk1/2 phosphorylation in damaged gastric tissue. It was indicated FA has good protection against ethanol-induced gastric mucosa injuries in mice and this effect was related to NF-κB and MAPK signalling pathways.

Protective role of fruits of Rosa odorata var. gigantea against WIRS-induced gastric mucosal injury in rats by modulating pathway related to inflammation, oxidative stress and apoptosis.

Objective: Rosa odorata var. gigantea is a popular medicinal plant. Some studies have demonstrated that ethanolic extract of the fruits of R. odorata var. gigantea (FOE) has gastroprotective properties. The aim of this study was to investigate the gastroprotective activity of FOE on water immersion restrained stress (WIRS)-induced gastric mucosal injury in a rat model and elucidate the possible molecular mechanisms involved. Methods: A rat stress ulcer model was established in this study using WIRS. After rats were treated with FOE orally for 7 d, the effect of FOE treatment was analyzed by hematoxylin and eosin (H&E) staining, and the changes of inflammatory factors, oxidative stress factors, and gastric-specific regulatory factors and pepsin in the blood and gastric tissues of rats were examined by ELISA assay. Molecular mechanism of FOE was investigated by immunohistochemical assay and Western blot. Results: Compared with the WIRS group, FOE could diminish both the macroscopic and microscopic pathological morphology of gastric mucosa. FOE significantly preserved the antioxidants glutathione peroxidase (GSH-PX), superoxide dismutase (SOD) and catalase (CAT) contents; anti-inflammatory cytokines interleukin-10 (IL-10) and prostaglandin E2 (PGE2) levels as well as regulatory factors tumor necrosis factor-α (TGF-α) and somatostatin (SS) contents, while decreasing malondialdehyde (MDA), nitric oxide synthase (iNOS), tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), gastrin (GAS) and endothelin (ET) levels. Moreover, FOE distinctly upregulated the expression of Nrf2, HO-1, Bcl2 and proliferating cell nuclear antigen (PCNA). In addition, FOE activated the expression of p-EGFR and downregulated the expression of NF-κB, Bax, Cleaved-caspase-3, Cyto-C and Cleaved-PARP1, thus promoting gastric mucosal cell survival. Conclusion: The current work demonstrated that FOE exerted a gastroprotective activity against gastric mucosal injury induced by WIRS. The underlying mechanism might be associated with the improvement of anti-inflammatory, anti-oxidation and anti-apoptosis systems.

A Rapid Self-Assembling Peptide Hydrogel for Delivery of TFF3 to Promote Gastric Mucosal Injury Repair.

Self-assembled peptide-based nanobiomaterials exhibit promising prospects for drug delivery applications owing to their commendable biocompatibility and biodegradability, facile tissue uptake and utilization, and minimal or negligible unexpected toxicity. TFF3 is an active peptide autonomously secreted by gastric mucosal cells, possessing multiple biological functions. It acts on the surface of the gastric mucosa, facilitating the repair process of gastric mucosal damage. However, when used as a drug, TFF3 faces significant challenges, including short retention time in the gastric mucosal cavity and deactivation due to degradation by stomach acid. In response to this challenge, we developed a self-assembled short peptide hydrogel, Rqdl10, designed as a delivery vehicle for TFF3. Our investigation encompasses an assessment of its properties, biocompatibility, controlled release of TFF3, and the mechanism underlying the promotion of gastric mucosal injury repair. Congo red/aniline blue staining revealed that Rqdl10 promptly self-assembled in PBS, forming hydrogels. Circular dichroism spectra indicated the presence of a stable ß-sheet secondary structure in the Rqdl10 hydrogel. Cryo-scanning electron microscopy and atomic force microscopy observations demonstrated that the Rqdl10 formed vesicle-like structures in the PBS, which were interconnected to construct a three-dimensional nanostructure. Moreover, the Rqdl10 hydrogel exhibited outstanding biocompatibility and could sustainably and slowly release TFF3. The utilization of the Rqdl10 hydrogel as a carrier for TFF3 substantially augmented its proliferative and migratory capabilities, while concurrently bolstering its anti-inflammatory and anti-apoptotic attributes following gastric mucosal injury. Our findings underscore the immense potential of the self-assembled peptide hydrogel Rqdl10 for biomedical applications, promising significant contributions to healthcare science.

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.

Low dose administration of mature silkworm powder induces gastric mucosal defense factors in ethanol-induced gastric injury rat model.

Gastric mucosa is important to protect the gastric damage against external factors. We previously reported the gastro-protective effects of steamed and freeze-dried mature silkworm larval powder (SMSP) in ethanol-treated rats. However, the factors that promote mucosal formation still remain unclarified. In this study, we evaluated the effect of SMSP on the restoration and maintenance of gastric mucosal layer as well as anti-inflammatory response in ethanol-induced stomach injury in rats. A significant decrease of ulcer indexes, histopathological scores and pro-inflammatory cytokine levels was observed in SMSP-treated group. In addition, SMSP protected the mucosal layer from ethanol-induced gastric damage by increasing the expression of nitric oxide synthases and heat shock proteins, along with promoting genes related gastric mucosal protection and biosynthesis including mucin 5AC and trefoil factors. These results demonstrate that SMSP attenuates the pro-inflammatory responses and strengthens the gastric mucosal layer, thus exhibiting gastro-protective effect against ethanol-induced gastric injury in rats.

Role of spasmolytic polypeptide-expressing metaplasia in gastric mucosal diseases.

Spasmolytic polypeptide-expressing metaplasia (SPEM) is a trefoil factor 2-expressing metaplasia in the fundic glands that resembles the fundic metaplasia of deep antral glandular cells and arises mainly from transdifferentiation of mature chief cells as well as mucous neck cells or isthmic stem cells. SPEM participates in the regulation of gastric mucosal injury, including focal and diffuse injury. This review focuses on the origin, models, and regulatory mechanisms of SPEM and on its role in the development of gastric mucosal injury. We hope to provide new prospects for the prevention and treatment of gastric mucosal diseases from the perspective of cell differentiation and transformation.

Phenolic acids-rich fraction from Ficus drupacea leaves for the prevention and treatment of ethanol-induced gastric mucosal injury in rats.

Bioactivity-guided fractionation of F. drupacea Thunb. extract revealed that the water fraction (FDWF) increased pH of the artificial gastric juice from 1.2 to 5.67 ± 0.015. The gastroprotective effect of FDWF against ulcer induced by ethanol was evaluated in rats. In ulcerogenic rats, increase in the gastric juice volume and ulcer lesions, and decrease in the gastric pH were evident. However, pretreatment with FDWF (100 mg/kg b.wt., p.o.) significantly inhibited lesion index, reduced gastric juice volume by 56.09% and increased gastric pH value. When given after ethanol, the same dose of FDWF led to significant healing of the gastric ulcer, with 75.60% reduction of gastric juice volume, and increase in pH value. In both prophylactic and therapeutic-treated groups, the level of superoxide dismutase and reduced glutathione in gastric homogenate were increased, while that of malondialdehyde was decreased. Also, the levels of succinate dehydrogenase and lactate dehydrogenase were increased, while that of acid phosphatase was decreased. In addition, the inflammatory markers; IL-10 and PGE2 were significantly increased. The histopathological results confirmed the above findings and indicated that the antiulcer effect of FDWF is mediated, at least in part, through antioxidant and anti-inflammatory mechanisms. Twenty-three compounds were tentatively identified in FDWF using UPLC-PDA-ESI-MS/MS and most of them were found to be phenolic acid derivatives. FDWF was standardized to contain 23.66 ± 2.62 mg/g and 8.86 ± 0.29 mg/g of quinic acid and chlorogenic acid, respectively. Accordingly, FDWF is a potential natural product that could increase the healing of gastric mucosal injury and prevents the development of ethanol-induced gastric mucosal injury in rats.

The protective effect of quinoa on the gastric mucosal injury induced by absolute ethanol.

BACKGROUND: Gastric mucosal injury caused by ethanol is a common gastrointestinal disease. Quinoa (Chenopodium quinoa Willd.), as a nutrient-rich grain, plays a significant role in preventing and treating gastric mucosal damage. The present study aimed to explore the protective effect of quinoa on alcohol-induced gastric mucosal damage and its possible mechanism. RESULTS: The ethanol-induced gastric mucosal injury rat model was used for in vivo experiments and H2 O2 -induced GES-1 cells for in vitro experiments to elucidate the protective effect of quinoa. The results show that quinoa water extract can increase the superoxide dismutase level and decrease the malondialdehyde level in vitro and in vivo. Furthermore, quinoa also reduced the bleeding point and bleeding area in rats with ethanol-induced gastric mucosal injury and improved gastric histopathological changes. H2 O2 significantly increased the levels of inflammatory factors in GES-1 cells, which were markedly ameliorated by quinoa water extract. Likewise, quinoa water extract regulated the protein expression levels of Nrf2, Keap1, HO-1, p-IKK, and p-NF-κB through Nrf2 and nuclear factor-κB signaling pathways, reducing the production of oxidative stress and inflammation, thereby repairing the damaged gastric mucosa. CONCLUSION: The findings of this study demonstrated that quinoa shows protective effect against ethanol-induced gastric mucosal injury through its anti-inflammatory and anti-oxidant effects. We propose that our research will provide a reference for quinoa as a functional food. © 2022 Society of Chemical Industry.

Effect of electroacupuncture on the repair of stress ulcer injury in neurocritical patients: A randomized clinical trial.

Background: Stress ulcer (SU) is one of the main causes of prolonged hospital stay, poor prognosis, and increased mortality in critically ill patients. This study aimed to investigate the effect of electroacupuncture (EA) on SU in patients with severe neurological diseases and explore its possible mechanisms. Methods: Taking patients with SU in adult neurocritical care as the research object, they were randomly divided into the EA group and the control group. Through the perioperative EA intervention, the following indicators were documented: main observation indicator (the effective rate of SU treatment), secondary observation indicators (gastric juice pH, gastric juice occult blood test, and stool occult blood test), related mechanisms [repair factors trefoil factor family 2 (TFF2), vascular endothelial growth factor (VEGF), and heat shock protein 70 (HSP70)], complications during hospitalization, and intensive care unit (ICU) stay time. Results: Compared with the control treatment, EA increased the effective rate of SU treatment (85.4% for the EA group, 57.5% for the control group, risk difference: 27.9% (95% CI: 8.3%-45.1%); P < 0.01). EA increased the success rate of gastric juice pH treatment on days 1, 2, and 3 (P < 0.01 for day 1, P < 0.05 for days 2 and 3). EA lowered the positive rate of gastric occult blood test on days 1 and 3 (all P-values < 0.05) and the positive rate of fecal occult blood test on day 3 (P < 0.05). EA also reduced the ICU stay time (P < 0.01) and total hospitalization time (P < 0.05). Compared with day 0, all serum repair factors (VEGF, HSP70, and TFF2) of both groups significantly increased on days 1, 3, and 5 (all P-values < 0.01). Compared with the control group, VEGF in the EA group was increased on days 3 and 5 (all P-values < 0.01); HSP70 was increased on days 1, 3, and 5 (P < 0.05 for day 1, P < 0.01 for days 3 and 5); and TFF2 was increased on days 1, 3, and 5 (all P-values < 0.01). Conclusion: Electroacupuncture promoted the repair of SU damage in severe neurological disease, and its effect was related to enhancing the expression of gastric mucosal repair factors. Clinical trial registration: [https://www.chictr.org.cn/showprojen.aspx?proj=127012], identifier [ChiCTR2100046701].

Protective Effect of Polyphenols Purified from Mallotus oblongfolius on Ethanol-Induced Gastric Mucosal Injury by Regulating Nrf2 and MAPKs Pathways.

Mallotus oblongifolius (MO), which is rich in polyphenols, is a characteristic tea resource with medicinal value. In this study, a total of 45 polyphenolic components of MO, including narirutin, isoquercitrin, rutin and digallic acid, were identified by UPLC-Q-TOF/MS analysis. In addition, the gastroprotective effect of Mallotus oblongifolius polyphenols (MOP) on ethanol-induced gastric mucosal injury in rats was investigated. The rats received anhydrous ethanol after continuous gavage of MOP or lansoprazole for one week. In addition, the macro- and micro-damage induced by ethanol in the gastric tissue was significantly reduced after MOP pretreatment for one week. Further analysis showed that MOP prevented ethanol-induced acute gastric mucosal injury by increasing the expression of antioxidant enzymes (SOD, CAT, GSH-Px) and decreasing the expression of reactive oxygen species (ROS), lipid oxidation product (MDA) and myeloperoxidase (MPO). Meanwhile, MOP inhibited the phosphorylation of p38/ERK/JNK and promoted the activation of the Nrf2 pathway. These results suggested that MOP may be a promising therapeutic target for the prevention of ethanol-induced gastric mucosal injury by improving oxidative stress, inhibiting the p38/ERK/JNK signaling pathways and activating Nrf2 expression.

The tibetan medicine Zuozhu-Daxi can prevent Helicobacter pylori induced-gastric mucosa inflammation by inhibiting lipid metabolism.

BACKGROUND: Tibetan medicine has been used in clinical practice for more than 3800 years. Zuozhu-Daxi (ZZDX), a classic traditional Tibetan medicine, has been proved to be effective in the treatment of digestive diseases, such as chronic gastritis, gastric ulcer, etc. Helicobacter pylori (H. pylori), one of the most common pathogenic microbes, is regarded as the most common cause of gastritis. Researching on the effects of ZZDX on H. pylori-induced gastric mucosa inflammation could provide more evidences on H. pylori treatment and promote the development of Tibetan medicine. This study aimed to explore whether ZZDX could rescue H. pylori-induced gastric mucosa inflammation and its mechanism. METHODS: Male C57BL/6 mice were infected with H. pylori, and orally treated with ZZDX to rescue gastric mucosa inflammation induced by H. pylori infection. Pathology of gastric mucosa inflammation was evaluated under microscopy by hematoxylin-eosin (HE) staining. The infection status of H. pylori was evaluated by immunohistochemical (IHC) staining. The reactive oxygen species (ROS) level in serum was evaluated using a detection kit. IL-1α, IL-6, and PGE2 expression levels in serum were measured using ELISA. IL-1α, IL-8, TNF-α, and NOD1 expression levels in gastric tissues were measured using real-time PCR. RNA sequencing and gene certification of interest were performed to explore the mechanisms in vivo and in vitro. RESULTS: The results showed that ZZDX could significantly inhibit H. pylori-induced gastric mucosa inflammation using HE staining. IL-1α, IL-6, and PGE2 expression levels in serum were significantly decreased after treatment with ZZDX. ZZDX treatment significantly decreased the mRNA expression of IL-8 induced by H. pylori infection in gastric tissues. Elovl4, Acot1 and Scd1 might be involved in the mechanisms of ZZDX treatment. However, the H. pylori infection status in the gastric mucosa was not reduced after ZZDX treatment. CONCLUSIONS: ZZDX reversed gastric mucosal injury and alleviated gastric mucosa inflammation induced by H. pylori infection.

Anti-Inflammatory Effect of Korean Propolis on Helicobacter pylori-Infected Gastric Mucosal Injury Mice Model.

Propolis, a natural resinous substance obtained from a variety of buds and plants, has been reported to possess various biological functions. Several recent studies have demonstrated the inhibitory effects of propolis on the growth of Helicobacter pylori (H. pylori) in vitro; however, current research efforts on Korean propolis (KP) remain insufficient especially in vivo. Our study aims to investigate the anti-inflammatory effect and molecular mechanism of KP on mouse gastric mucosa during H. pylori infection. We examined an in vivo H. pylori-induced gastric mucosal injury mice model. We found that KP inhibited the growth of H. pylori and attenuated the expression of H. pylori virulence factors such as cytotoxin-associated gene A, encoding urease A subunit, surface antigen gene and neutrophil-activating protein A. Moreover, KP reduced both gross lesions and pathological scores in H. pylori-challenged mice. In addition, KP markedly restrained the production of pro-inflammatory cytokines and nitric oxide levels compared with an untreated H. pylori-infected group. In particular, we found that KP repressed the phosphorylation of IκBα and NF-κB p65 subunit, and subsequently suppressed their downstream target genes. Taken together, these findings demonstrate the beneficial effects of KP on inflammation through the inhibition of NF-κB signaling as well as inhibition of H. pylori growth in a mouse model infected with H. pylori. This suggests the potential application of KP as a natural supplement for patient's suffering from gastric mucosal injury caused by H. pylori infection.

Aspirin in combination with gastrodin protects cardiac function and mitigates gastric mucosal injury in response to myocardial ischemia/reperfusion.

Myocardial ischemia/reperfusion (I/R) injury after percutaneous coronary intervention (PCI) is common in acute myocardial infarction. Aspirin is commonly prescribed as anti-thrombotic therapy with coronary heart disease (CHD). However, long-term use of aspirin causes severe gastric mucosal damage. Gastrodin is a Chinese natural medicine with anti-inflammatory and anti-oxidative properties. In this study, we investigated the effects of combined therapy with aspirin and gastrodin on the myocardial and gastric mucosal injury in response to myocardial I/R injury and underlying mechanisms using the Sprague-Dawley (SD) rat model. Our results demonstrated that myocardial I/R caused significant cardiac dysfunction and gastric mucosal damage. Administration of aspirin led to significantly reduce myocardial infarction size and myocardial enzyme release, as well as significantly improved cardiac function through exerting anti-inflammatory effects. However, aspirin exacerbated gastric mucosal damage by increasing the levels of inflammatory mediators and endothelin (ET) while reducing prostaglandin E2 (PGE2) levels. The combined treatment with aspirin and gastrodin not only significantly protected gastric mucosa by normalizing the expression levels of the inflammatory factors, ET and PGE2, but also significantly reduced myocardial infarction size and improved cardiac function by inhibiting inflammation in response to I/R. The combination therapy also dramatically down-regulated the levels of pyroptosis-related proteins in the myocardium and gastric mucosa. The combination therapy showed obviously reduced level of thromboxane B2 (TXB2), which was simultaneously accompanied with increased levels of the tissue plasminogen activator (t-PA). This suggested that gastrodin did not inhibit the anti-thrombotic function of aspirin. Accordingly, aspirin in combination with gasrtodin protected the structural and functional integrity of the heart and stomach by suppressing pyroptosis and inflammation. Therefore, combination of aspirin and gastrodin is a promising treatment for cardiac dysfunction and gastric mucosa injury after myocardial I/R.

Structural characterization and preventive effect on alcoholic gastric mucosa and liver injury of a novel polysaccharide from Dendrobium officinale.

In this study, a polysaccharide (DOP) with molecular weight of 8.25 × 105 Da and monosaccharide composition of mannose (Man) and glucose (Glc) at a molar ratio of 4.2: 1 was isolated from Dendrobium officinale. The preventive effect on alcoholic gastric mucosa and liver injury of DOP was also investigated. In vitro data exhibited that the IC50 values of 1, 1-diphenyl-2-picrylhydrazy (DPPH) radical scavenging ability and Fe2+ chelating capacity were 2.762 mg/mL and 6.667 mg/mL, respectively. Both the alcoholic gastric mucosal injury (AGMI) and alcoholic liver injury (ALI) animal models were used to investigate the gastrotrophic and hepatoprotective abilities of DOP. After administration of DOP, both gastric mucosal index (TNF-α, IL-6, PGE2, SOD, and MDA) and hepatic indicators (ALT, AST, SOD and MDA) improved compared to non-DOP groups. Histopathological results displayed that the DOP groups improved gastric epithelial defect and inflammatory cell redness caused by AGMI, and decreased vacuolization, hepatocyte necrosis and fibrosis caused by ALI. The results might be related to adjusting inflammatory factors, eliminating free radicals, and inhibiting lipid peroxidation capacities. These results manifested that DOP may be a therapeutic reagent to attenuate alcohol gastric mucosal and liver injury.

Biopsy Confirmed Doxycycline Induced Gastric Mucosal Injury.

Doxycycline (DOX) is a tetracycline antibiotic that is prescribed for treating a variety of infections involving the skin, respiratory tract, and urogenital system. Adversely, esophageal mucosal injury due to DOX is well described; however, gastric mucosal injury is less commonly reported and may result in severe gastrointestinal hemorrhage and occasionally, perforation. In most reported cases of DOX-induced gastric lesions, patients are symptomatic upon presentation leading to endoscopic evaluation and diagnosis with biopsy. However, severe gastric insults may go unrecognized in rare cases of asymptomatic patients, increasing the risk of mortality.

Comparison of the Degree of Gastric Mucosal Injury between Patients Who Are Receiving Dual Antiplatelet Therapy or Single Antiplatelet Therapy.

BACKGROUND: Patients taking low-dose aspirin have a higher incidence of gastroduodenal ulcers and higher risk of upper gastrointestinal bleeding than patients who do not. Thienopyridine antiplatelet agents may similarly cause bleeding gastroduodenal erosions and ulcers. The incidence of gastrointestinal bleeding is reported to be higher when these antithrombotic drugs are used in combination. Until now, most studies have focused on bleeding, and no study has compared the degree of gastric mucosal injury between patients receiving dual antiplatelet therapy (DAPT) and those receiving single antiplatelet therapy (SAPT) in real-world clinical practice. AIM: Our objective was to compare the degree of gastric mucosal injury in patients taking low-dose aspirin in combination with clopidogrel (one of the thienopyridine antiplatelet agents) with that of patients who were taking aspirin or clopidogrel as a single agent. METHODS: Patients who were taking aspirin and/or clopidogrel and who underwent scheduled esophagogastroduodenoscopy between April 2015 and March 2020 were enrolled in this study. Endoscopic images were reviewed retrospectively, and the degree of gastric mucosal injury was assessed with the modified Lanza score (m-Lanza score). The m-Lanza score was compared between DAPT patients taking aspirin and clopidogrel and SAPT patients taking either aspirin alone or clopidogrel alone. RESULTS: The m-Lanza scores of the DAPT group, the aspirin group, and the clopidogrel group were 1.67 ± 1.81 (mean ± standard deviation), 0.95 ± 1.61, and 0.72 ± 1.29, respectively. The m-Lanza score of the DAPT group tended to be higher than that of the aspirin group (p = 0.06) and was significantly higher than that of the clopidogrel group (p = 0.03). CONCLUSION: The degree of gastric mucosal injury in DAPT patients was significantly higher than that in patients using clopidogrel alone and tended to be higher than that in patients using aspirin alone in real-world clinical practice.

Antarctic krill (Euphausia superba) oil modulatory effects on ethanol-induced acute injury of the gastric mucosa in rats.

Antarctic krill oil (KO) prepared using supercritical carbon dioxide extraction and characterized using gas chromatography-mass spectrometry was used to investigate its preventive effect on ethanol-induced gastric tissue damage in a rat model in vivo. KO characterization showed that 74.96% of the unsaturated fatty acids consist of oleic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Rats pre-treated with KO (100, 200, and 500 mg/kg) showed mitigated oxidative stress through enhanced antioxidant enzyme superoxide dismutase (SOD) and reducing enzymes malondialdehyde (MDA) and myeloperoxidase (MPO) in gastric mucosal injury induced by ethanol. Additionally, the secretion of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß), the expression of the IκBα/NF-κB signaling pathway, and nitric oxide (NO) production was suppressed. The results also demonstrated a significant decrease in histological injury and hemorrhage scores in a dose-dependent manner in the KO range. Therefore, KO has potential as a food supplement to alleviate ethanol-induced acute gastric mucosal injury.