Acute Gastric Inflammation Research Articles

Cinnamaldehyde: An effective component of Cinnamomum cassia inhibiting Helicobacter pylori

Ethnopharmacological relevanceCinnamomum cassia Presl (Cinnamomum cassia) is a common traditional Chinese medicine, which can promote the secretion and digestion of gastric juice, improve the function of gastrointestinal tract. Cinnamaldehyde (CA) is a synthetic food flavoring in the Chinese Pharmacopoeia. Aim of the studyThis study aimed to search for the active ingredient (CA) of inhibiting H. pylori from Cinnamomum cassia, and elucidate mechanism of action, so as to provide the experimental basis for the treatment of H. pylori infection with Cinnamomum cassia. Materials and methodsIt's in vitro and in vivo pharmacological properties were evaluated based on minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and an acute gastric inflammation model in mice infected with H. pylori. Drug safety was evaluated using the CCK8 method and high-dose administration in mice. The advantageous characteristics of CA in inhibiting H. pylori were confirmed using acidic conditions and in combination with the antibiotics. The mechanism underlying the action of CA on H. pylori was explored using scanning electron microscopy (SEM), adhesion experiments, biofilm inhibition tests, ATP and ROS release experiments, and drug affinity responsive target stability (DARTS) screening of target proteins. The protein function and target genes were verified by molecular docking and Real-Time quantitative reverse transcription PCR (qRT-PCR). ResultsThe results demonstrated that CA was found to be the main active ingredient against H. pylori in Cinnamomum cassia in-vitro tests, with a MIC of 8–16 μg/mL. Moreover, CA effectively inhibited both sensitive and resistant H. pylori strains. The dual therapy of PPI + CA exhibited remarkable in vivo efficacy in the acute gastritis mouse model, superior to the standard triple therapy. DARTS, molecular docking, and qRT-PCR results suggested that the target sites of action were closely associated with GyrA, GyrB, AtpA, and TopA, which made DNA replication and transcription impossible, then leading to inhibition of bacterial adhesion and colonization, suppression of biofilm formation, and inhibition ATP and enhancing ROS. ConclusionsThis study demonstrated the suitability of CA as a promising lead drug against H. pylori, The main mechanisms can target GyrA ect, leading to reduce ATP and produce ROS, which induces the apoptosis of bacterial.

The G-Protein-Coupled Bile Acid Receptor Gpbar1 (TGR5) Inhibits Gastric Inflammation Through Antagonizing NF-κB Signaling Pathway.

Gpbar1 (TGR5), a membrane-bound bile acid receptor, is well-known for its roles in regulation of energy homeostasis and glucose metabolism. Here, we show that mice lacking TGR5 were much more susceptible to lipopolysaccharide (LPS)-induced acute gastric inflammation than wild-type (WT) mice and TGR5 is a negative regulator of gastric inflammation through antagonizing NF-κB signaling pathway. We found that the treatment of TGR5 ligands 23(S)-mCDCA and GPBARA (3-(2-Chlorophenyl)-N-(4-chlorophenyl)-N,5-dimethylisoxazole-4-carboxamide) suppressed gene and protein expression mediated by NF-κB signaling. TGR5 overexpression with ligand treatment inhibited gene expression of interferon-inducible protein 10 (IP-10), TNF-α, and chemoattractant protein-1 (MCP-1) induced by LPS. Furthermore, we revealed that TGR5 activation antagonized NF-κB signaling pathway through suppressing its transcription activity, the phosphorylation of IκBα and p65 translocation, which suggests that TGR5 antagonizes gastric inflammation at least in part by inhibiting NF-κB signaling. These findings identify TGR5 as a negative mediator of gastric inflammation that may serve as an attractive therapeutic tool for human gastric inflammation and cancer.

Anti-Inflammatory and Gastroprotective Activities of C udrania Tricuspidata Leaf Extract Against Acute HCl/Ethanol-Induced Gastric Mucosal Injury in Sprague-Dawley Rats

We investigated the inhibitory effect of Cudrania tricuspidata ethanol 10% extract (CTL10) on gastric inflammation induced by acute ethanol treatment in Sprague-Dawley rats. After oral administration of CTL10 (100 or 300 mg/kg) for 7 days, acute gastric inflammation was induced by 70% ethanol and 0.15 M HCl. After 1 h of ethanol administration, the animals were sacrificed. Pretreatment with CTL10 showed attenuation of gastric mucosal injury, hemorrhages and gastric juice secretion induced by ethanol administration. Oral administration of CTL10 significantly decreased the levels of lipid peroxidation and increased superoxide dismutase activity. Additionally, pretreatment with 300 mg/kg CTL10 significantly decreased the expression of nuclear factor-κB, cyclooxygenase-2, interferon-γ, interleukin-6 and tumor necrosis factor-α compared with the gastric inflammation group. Based on this study, CTL10 may be considered a potential agent to control acute gastric inflammation induced by alcohol through the antioxidative effect of CTL10. Practical Applications Ethanol directly and dose-dependently impairs the gastric mucosal barrier, and the molecular mechanisms underlying ethanol-induced gastric inflammation remain incompletely understood. However, there is evidence that free radical production and oxidative stress play a major role in the pathogenesis of acute gastric inflammation by ethanol. We investigated the inhibitory effect of Cudrania tricuspidata ethanol 10% extract (CTL10) on gastric inflammation induced by acute ethanol treatment in Sprague-Dawley (SD) rats. We found that CTL10 has inhibitory effects on gastric inflammation induced by acute ethanol treatment in SD rats. Although the exact mechanism underlying these effects is unclear, the effects on acute gastric inflammation suggest a mechanism involving the antioxidant properties of C. tricuspidata. C. tricuspidata may be a new alternative for the clinical management of gastric inflammation while serving as an antioxidant against oxidative stress.

Mesenchymal Stem Cells Utilize CXCR4–SDF-1 Signaling for Acute, but Not Chronic, Trafficking to Gastric Mucosal Inflammation

Background Helicobacter infection is the main risk factor in developing gastric cancer. Mesenchymal stem cells (MSCs) are non-hematopoietic stromal cells, which are able to differentiate into different cell lineages. MSC contribute to cancer development by forming the tumor directly, contributing to the microenvironment, or by promoting angiogenesis and metastasis. CXCR4/SDF-1 axis is used by MSC in trafficking, homing, and engraftment at chronic inflammation sites, and plays an important role in tumorigenesis.AimTo determine if CXCR4 receptor has a role in MSC contribution to the development of Helicobacter-mediated gastric cancer.MethodsSDF-1 and CXCR4 expression in mouse gastric mucosa in the setting of acute and chronic inflammation was measured using RT-PCR. Mouse culture-adapted MSC express CXCR4. Wild-type C57BL/6 mice infected with Helicobacter felis for 6 months or controls were given IV injections of CXCR4 knock-down MSC. Animals were followed for another 4 months. Homing of MSC in the stomach was quantified using RT-PCR. MSC differentiation into gastric epithelia lineages was analyzed using immunohistochemistry and fluorescent in situ hybridization.ResultsCXCR4 and SDF-1 are both upregulated in the settings of Helicobacter-induced chronic gastric inflammation. CXCR4 is fully required for homing of MSC to the stomach in acute gastric inflammation, but only partially in Helicobacter-induced gastric cancer. MSC lead to gastric intraepithelial neoplasia as early as 10 months of Helicobacter infection.ConclusionsOur results show that MSC have a tumorigenic effect by promoting an accelerated form of gastric cancer in mice. The engraftment of MSC in chronic inflammation is only partially CXCR4-dependent.

Inhibitory effect of Canavalia gladiata extract on gastric inflammation induced by acute ethanol treatment in SD rats

We investigated the inhibitory effect of Canavalia gladiata water extract (CGW) on ethanol‐induced gastric inflammation, specifically on gastric acid secretion and gastric mucosal damage in Sprague‐Dawley (SD) rats. The possible mechanisms of CGW actions via ROS was also further determined for antioxidant effects. Rats were divided into four groups : saline(G1), gastric inflammation plus saline(G2), gastric inflammation plus Lansoprazole 30mg/kg b.w(G3), gastric inflammation plus CGW 250mg/kg b.w(G4), gastric inflammation plus CGW 500mg/kg b.w(G5). After oral administration of either saline, Lansoprazole or CGW for 7 days, acute gastric inflammation was induced by oral administration of 1mL of 70% ethanol and 0.15M HCl at groups G2,G3,G4 and G5. After 1h on ethanol administration, all animals were sacrificed. Gastric acid secretion and gastric mucosal injury were significantly decreased in G3 when compared to that of G2. And groups pretreated with CGW (G4, G5) caused a significant decrease in gastric acid secretion and gastric mucosal injury in a dose dependant manner. To examine the regulatory factors related inflammation, NF‐kB, COX‐1, COX‐2 and cytokines were measured by immuno‐histochemistry and ELISA. The expression of NF‐kB, COX‐1 and COX‐2 were clearly decreased in G3 and G5 compared with the G2. Additionally, cytokines was significantly decreased in G3 and G5. We next examined the levels of MDA and SOD activity related in antioxidative effects. Oral administration of CGW significantly decreased levels of MDA and SOD activity was dramatically increased. In conclusion, our data show that CGW has inhibitory effects on gastric inflammation induced by acute ethanol treatment in SD rat. Although the exact mechanism underlying these actions is unclear, the effects on acute gastric lesions suggest a multifactorial mechanism probably involving the antioxidant properties of CGW.

Acute gastric inflammation in Mongolian gerbils depends on the status of cag pathogenicity island of Helicobacter pylori

Acute gastric inflammation in Mongolian gerbils depends on the status of cag pathogenicity island of Helicobacter pylori

Helicobacter pylori cagA+ strains and dissociation of gastric epithelial cell proliferation from apoptosis.

Infection with Helicobacter pylori induces chronic gastritis in virtually all infected persons, and such gastritis has been associated with an increased risk of developing gastric cancer. This risk is further enhanced with cagA+ (positive for cytotoxin-associated gene A) H. pylori strains and may be a consequence of induced gastric cell proliferation and/or alteration in apoptosis (programmed cell death) in the gastric epithelium. To determine whether the H. pylori cagA genotype and another virulence-related characteristic, the vacA (vacuolating cytotoxin A) s1a genotype, differentially affect epithelial cell proliferation, apoptosis, and the histologic parameters of inflammation and injury, we quantitated these characteristics in infected and uninfected persons. Fifty patients underwent upper gastrointestinal endoscopy, and biopsy specimens were taken. Apoptotic cells in the specimens were quantitated after terminal deoxynucleotidyl transferase labeling of DNA fragments with digoxigenin-deoxyuridine triphosphate; epithelial cell proliferation was scored by immunohistochemical analysis of the proliferation-associated antigen Ki-67. Antibodies directed against H. pylori and CagA protein were measured in the serum of patients by means of enzyme-linked immunosorbent assays. Analysis of H. pylori genomic DNA, by use of the polymerase chain reaction, was performed to determine the cagA and vacA genotypes. Acute and chronic inflammation, epithelial cell degeneration, mucin depletion, intestinal metaplasia, glandular atrophy, and vacuolation were each scored in a blinded manner. Reported P values are two-sided. Persons harboring cagA+ strains (n = 20) had significantly higher gastric epithelial proliferation scores than persons infected with cagA-strains (n = 9) or uninfected persons (n = 21) (P = .025 and P<.001, respectively), but the difference in cell proliferation between the latter two groups was not statistically significant. The number of apoptotic cells per 100 epithelial cells (apoptotic index) in persons infected with cagA+ strains was lower than in persons infected with cagA-strains (P = .05). Apoptotic indices in the cagA+ group were similar to those in the uninfected group (P = .2). Epithelial cell proliferation was significantly correlated with acute gastric inflammation, but only in the cagA+ group (r = .44; P = .006). The cagA+ and vacA s1a genotypes were found to be concordant, confirming the close relationship between these virulence-related genotypes. Gastric mucosal proliferation was significantly correlated with the severity of acute gastritis in persons infected with cagA+ vacA s1a strains of H. pylori. This increased proliferation was not accompanied by a parallel increase in apoptosis. Increased cell proliferation in the absence of a corresponding increase in apoptosis may explain the heightened risk for gastric carcinoma that is associated with infection by cagA+ vacA s1a strains of H. pylori.

Helicobacter pylori and atrophic gastritis: importance of the cagA status.

Infection with Helicobacter pylori is a major risk factor for the development of atrophic gastritis and gastric cancer. H. pylori strains can differ with respect to the presence of cagA (cytotoxin-associated gene A), a gene encoding a high-molecular-weight immunodominant antigen. H. pylori strains possessing cagA have been associated with enhanced induction of acute gastric inflammation. We investigated the relationship between cagA status and the development of atrophic gastritis in a cohort of subjects infected with H. pylori. Gastrointestinal endoscopy with biopsy sampling was used to study the natural history of gastritis in 58 subjects infected with H. pylori. Biopsy specimens were obtained before and after a mean follow-up period of 11.5 years (range, 10-13 years). The cagA status of each individual was determined at the follow-up visit with the use of an enzyme-linked immunosorbent assay designed to detect the presence of serum immunoglobulin G directed against the CagA protein. Two-sided Fisher's exact tests, McNemar's tests, Student's t tests, and Wilcoxon sum rank tests were used to analyze the data. Twenty-four (41%) of the 58 evaluated subjects had serum antibodies against CagA (i.e., they were cagA positive), and 34 subjects were cagA negative. At the initial visit, moderate to severe atrophic gastritis was observed in eight (33%) of the cagA-positive subjects and in six (18%) of the cagA-negative subjects. At that time, positive cagA status and gastric atrophy were not significantly related (P = .22; Fisher's exact test; odds ratio [OR] 2.33; 95% confidence interval [CI] = 0.58-9.65). During follow-up, 16 (36%) of the 44 initially atrophy-negative subjects developed atrophic gastritis (eight [50%] of 16 cagA-positive subjects versus eight [29%] of 28 cagA-negative subjects; P = .20, Fisher's exact test; relative risk [RR] = 1.75; 95% CI = 0.82-3.76). In six of these 16 subjects (five cagA positive versus one cagA negative), atrophic gastritis was accompanied by the development of intestinal metaplasia (i.e., a change in the type of specialized cells present) (P = .02; Fisher's exact test; RR = 9.06; 95% CI = 1.16-71.0). One of the initially atrophy-negative, cagA-positive subjects developed early gastric cancer. Four (29%) of the 14 subjects initially diagnosed with atrophic gastritis showed regression of atrophy during follow-up (one cagA positive and three cagA negative). Therefore, at the end of follow-up, 15 (62%) of the 24 cagA-positive subjects had atrophic gastritis compared with 11 (32%) of the 34 cagA-negative subjects (P = .02; Fisher's exact test; OR = 3.48; 95% CI = 1.02-12.18). Infection with cagA-positive H. pylori strains is associated with an increased risk for the eventual development of atrophic gastritis and intestinal metaplasia.

Nitrofurans in the treatment of gastritis associated with Campylobacter pylori

We conducted a double-blind, placebo-controlled, randomized treatment study in Peruvian adults with antral gastritis associated with Campylobacter pylori. Patients received either 400 mg of furazolidone (n = 14), 400 mg of nitrofurantoin (n = 24), or a placebo (n = 31) for 14 days. Endoscopy was carried out at baseline, 1 day after ceasing therapy, and 6 wk after the end of treatment to verify colonization by C. pylori and determine the extent of gastric inflammation. Treatment with nitrofurantoin or furazolidone markedly reduced or, in some cases, cleared C. pylori from the antrum (p < 0.0005 compared with placebo). Resolution of acute gastric inflammation, as evidenced by decreased polymorphonuclear leukocyte infiltration and regeneration of the mucus layer, paralleled the reduction in bacterial colonization (p < 0.005 compared with placebo). A high percentage of patients experienced relapse (recolonization by C. pylori and return to pretreatment levels of gastritis) within 6 wk after cessation of treatment. Significant relief of dyspeptic symptoms was not evident during the study.