Gastritis Model Research Articles

Selectively Antagonizing the NOD1-Mediated Inflammatory Signaling Pathway Mitigates the Gastric Inflammation Induced by Helicobacter pylori Infection.

Helicobacter pylori (H. pylori) infection is characterized by the complex interplay between H. pylori and gastric disorders. It has been established that NOD1 can be activated by the peptidoglycan (PGN) present in the cell wall of H. pylori, serving as a key mediator of inflammation and initiating the RIP2/NF-κB and MAPK inflammatory signaling pathways. In this article, we reported on the development of a 2-chloroquinazolin-4-ol derivative 66 as a potent and selective antagonist of both human and mouse NOD1, which effectively inhibited the expression of inflammatory cytokines (IL-6, TNF-α) and chemokines (CXCL1, CXCL8) in immune and epithelial cells, as well as inflammatory cytokines (KC, IL-6) in a H. pylori-induced murine model of gastritis following oral administration. This study laid a foundation for treating gastritis induced by H. pylori infection.

Identification of the Biomarkers for Chronic Gastritis with TCM Damp Phlegm Pattern by Using Tongue Coating Metabolomics.

This study aimed to establish a model for identifying chronic gastritis with the traditional Chinese medicine damp phlegm pattern by examining metabolite changes in the tongue coating of patients. It also explored the role of metabolic pathways in the pathogenesis of this condition. This cross-sectional study involved 300 patients diagnosed with chronic gastritis. Of these, 200 patients exhibited the damp phlegm pattern, while 100 did not. Metabolomic methods employing GC-TOF-MS and UHPLC-QE-MS were utilized to identify various metabolites in the tongue coating of patients. An identification model for chronic gastritis with the damp phlegm pattern was created based on ROC curves derived from differential biomarkers. Additionally, 50 samples not included in model construction were collected for external validation. Comparison of the damp phlegm pattern group with the non-damp phlegm pattern group revealed a total of 116 differential metabolites. Among these, lipids and lipid-like compounds were most abundant, comprising 27 types, which included four lipid metabolites related to sphingomyelin metabolism. The ROC model, which included phenol, 2.6-diaminoheptanedioic acid, and N-hexadecanoyl pyrrolidine, demonstrated the highest accuracy, with accuracy, sensitivity, and specificity metrics of 94.0%, 91.0%, and 87.0%, respectively. Furthermore, external validation using tongue coating metabolites from 50 patients revealed accuracy, sensitivity, and specificity in the validation set of 93.9%, 90.6%, and 83.3%, respectively. Differential metabolites between patients with the damp phlegm pattern and those without are primarily lipids and lipid-like compounds. N-hexadecanoyl pyrrolidine, phenol, and 2.6-diaminoheptanedioic acid may serve as potential biomarkers for chronic gastritis characterized by the damp phlegm pattern.

A combination of carbonates and Opuntia ficus-indica extract protects esophageal cells against simulated acidic and non-acidic reflux in vitro

Buffering of stomach acid by antacids is a well-established symptomatic therapy for heartburn. In addition, preparations from prickly pear (Opuntia ficus-indica) have been shown to reduce tissue damage in experimental gastritis models and to attenuate gastrointestinal discomfort in patients. Both active principles have been included in a fixed-combination product for symptomatic treatment of heartburn containing carbonate antacids (CaCO3 and MgCO3) and an extract from Opuntia ficus-indica cladodes. The aim of the study was to characterize the acid neutralization and esophageal cell protective activities of the product and its individual active ingredients in a set of in vitro assays. Acid neutralization was assessed in a simulated stomach model. Protective activity of individual constituents and in combination was analyzed in an esophageal cell line (COLO-680 N) exposed to low pH and deoxycholic acid to simulate acidic and non-acidic reflux challenge. The combination product protected cells against low pH mediated cytotoxicity via acid neutralization by carbonates. Opuntia extract itself and the combination product attenuated bile acid-induced cell irritation as measured by reduced release of proinflammatory interleukin-6 and -8. In conclusion, addition of Opuntia extract to a mineral antacid provides dual protection against acidic and non-acidic simulated reflux challenge.

Endoscopic appearances of gastric mucosa in different endoscopic models according to H. pylori infection status.

H. pylori infection has been recognized as a type 1 carcinogen of the gastric malignancy; therefore, early diagnosis and treatment are the corner stone of eradication. Recent findings have also shown that atrophy and intestinal metaplasia remain after successful eradication, which moderately increases the risk of gastric cancer compared with those who have never infected, so the evaluation of gastric mucosa during gastroscopy is important. We aimed to describe and summarize the reliable literature and proposed features of H. pylori infection status and gastritis in research on newly developed endoscopic models that influence clinical practice. In the result, conventional white light endoscopic, image-enhanced endoscopic models, and studies related to the Kyoto classification of gastritis were searched and reviewed. Kyoto classification of gastritis and modified Kyoto classification scoring model for gastritis using conventional white light image (CWLI) endoscopy is an effective tool for evaluating current H. pylori infection status, past infections, eradications, noninfections, and pre-cancerous conditions. This model is widely used, low cost, and time-efficient, and is supported by recent findings. Advanced image-enhanced endoscopic models combined with magnifying endoscopy provide more clear endoscopic features for H. pylori infection status and early gastric cancer. According to H pylori infection status, endoscopic prediction of gastric mucosal surface architecture analysis is possible, which influences clinical management. Endoscopic models might lead us to accurate and early diagnose of H. pylori infection status and may not be effective only for the eradication of H. pylori infection but also in the detection of early gastric cancer status.

Application of Immunohistochemistry in Rat Models of Erosive Gastritis

Application of Immunohistochemistry in Rat Models of Erosive Gastritis

Comparison of gut microbiota immunity and pathology in specific-pathogen-free chickens with glandular and muscular gastritis using different methods.

The objective of this study is to review different methods to screen for the optimal model for preventing and treating chicken glandular and muscular gastritis syndrome. Twenty-four 40-day-old specific pathogen-free (SPF) chickens were randomly allocated into four groups (N = 6): polyethylene glycol + ammonium chloride group (M1 group), acetic acid + rhubarb group (M2 group), polyethylene glycol + rhubarb group (M3 group), and control group. The control group had free access to water, while the remaining groups received different doses of molding reagents added to their drinking water. The animal models were assessed based on clinical manifestations, histopathology findings, serological analysis, and composition of intestinal microbiota to establish an optimal approach for constructing an avian model of glandular and muscular gastritis. The SPF chickens in each model group exhibited typical symptoms of glandular and muscular gastritis, poor spirit, yellow loose stools with undigested feed, and enlargement and ulceration of the glandular and muscular stomach. Among these groups, the M3 group had the highest incidence rate of 100%. Compared to the control group, the body weight and body temperature of the chicken in the three model groups were reduced, and the glandular and muscular stomachs and duodenum showed different degrees of bleeding, mucosal abscission, and other pathological injuries. Additionally, the levels of serum IL-2 and α-amylase activity decreased while the content of IL-4 increased. After conducting 16s rDNA sequencing, it was observed that the abundance of Bacteroides, Faecalibacterium, and Ruminococcaceae UCG-014 was significantly increased in the model group compared to the control group. Conversely, there was a notable decrease in the levels of Megamonas and Lactobacillus, which are speculated to be associated with arachidonic acid metabolism, the NF-κB signaling pathway, and TNF signaling pathways. The combination of polyethylene glycol and rhubarb emerged as the most effective method for establishing the glandular and muscular gastritis model in SPF chickens. This constructed chicken model displayed distinct signs of damage to the glandular and muscular stomach, inflammatory response, and disturbance in the intestinal flora, thereby providing a foundation for future research on the prevention and treatment of this syndrome.

Catha edulis Leaves: Morphological Characterization and Anti-Inflammatory Properties in an In Vitro Model of Gastritis.

Khat leaves, indigenous to eastern Africa, have been chewed for centuries for their stimulant effects, attributed to alkaloids such as cathinone and cathine. Although associated with gastric disorders like gastritis and gastro-oesophageal reflux disease, the underlying molecular mechanisms remain unclear. This study aimed to examine the morpho-anatomy of khat leaves using light microscopy and histochemistry and to assess the effects of leaf extracts and alkaloids on human gastric epithelial cells (GES-1). The study identified specific cells in the palisade-spongy transition zone as storage sites for psychoactive alkaloids. Leaf extracts were prepared by mimicking the chewing process, including a prolonged salivary phase followed by a gastric phase. Cytotoxicity and cell viability were evaluated using LDH and MTT assays, respectively. Additionally, the impact on IL-8 secretion, a key chemokine in gastric inflammation, was analysed under normal and TNF-α-stimulated conditions. The results showed no increase in cytotoxicity up to 250 µg/mL. However, there was a significant decrease in cell metabolism and a reduction in both basal and TNF-α-induced IL-8 secretion, but cathinone and cathine were inactive. These findings suggest that khat may not directly cause the gastric issues reported in the literature, which would rather be attributed to other confounding factors, highlighting the need for further research to clarify its biological impacts.

Ginseng Berry Juice (GBJ) Regulates the Inflammation in Acute Ulcerative Mouse Models and the Major Bioactive Substances Are Ginsenosides Rb3, Rc, Rd, and Re.

Panax ginseng fruit is known to have various biological effects owing to its large amount of saponins such as ginsenosides. In the present study, ginseng berry juice was confirmed to be effective against acute inflammation. Ginseng berry juice was used for analysis of active constituents, antioxidant efficacy, and in vivo inflammation. A high-performance liquid chromatography method was used for analysis of ginsenosides. In an HCl/ethanol-induced acute gastric injury model, microscopic, immunofluorescent, and immunohistochemical techniques were used for analysis of inhibition of gastric injury and mechanism study. In a mouse model of acute gastritis induced with HCl/ethanol, ginseng berry juice (GBJ, 250 mg/kg) showed similar gastric injury inhibitory effects as cabbage water extract (CB, 500 mg/kg, P.O). GBJ dose-dependently modulated the pro-inflammatory cytokines such as Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), and Interleukin-13 (IL-13). GBJ inhibited the activation of Nuclear Factor kappa bB (NF-κB) and suppressed the expressions of cyclooxigenase-2 (COX-2) and prostaglandin 2 (PGE2). The anti-inflammatory effect of GBJ is attributed to ginsenosides which have anti-inflammatory effects. Productivity as an effective food source for acute gastritis was analyzed and showed that GBJ was superior to CB. In addition, as a functional food for suppressing acute ulcerative symptoms, it was thought that the efficacy of gastric protection products would be higher if GBJ were produced in the form of juice rather than through various extraction methods.

El efecto protector del extracto de Granada contra la úlcera gástrica experimental inducida por etanol en ratas

The Pomegranate (Punica granatum) is a commonly found fruit in the Mediterranean and Iran, which has a variety of uses including medicinal purposes, cosmetics, and as a spice in culinary applications. Pharmacological functions of Pomegranate include antioxidation, anti–tumor, anti–hepatotoxicity, anti–lipoperoxidation and antibacterial properties. The aim of this study was to evaluate the therapeutic efficacy of Pomegranate extract by utilizing its antioxidant activity in an experimental rat model of gastritis induced by ethanol. In the study, 24 female Wistar albino rats (180–200 g) were used. Gastritis in rats was induced using Ethanol. In experimental groups, Tumor necrosis factor–alpha, Myloperoxidase, Superoxide Dismutase and Malondialdehyde were examined for biochemical analyzes. Streptavidin peroxidase immunohistochemistry method was applied to gastric tissues with gastritis. A statistically significant difference was observed between Superoxide Dismutase and Meloperoxidase levels. CD8 and CD68 immunoreactivity was higher in the Ethanol group compared to the other groups. A decrease was observed in CD8 and CD68 positive immunoreactivity in Ethanol+Pomegranate extract group compared to Ethanol group. The study found that the immunoreactivity of MHC–I and MHC–II was found in specific locations, namely intraepithelial lymphocytes located in the epithelium, some capillary vessel endothelium, and connective tissue. Changes in anti–oxidative stress markers such as Superoxide Dismutase and Myloperoxidase contributed to the mucosal protective effect of Pomegranate extract in Ethanol–induced gastritis.

Rat Experimental Autoimmune Gastritis Model

ABSTRACT Background Autoimmune gastritis (AIG) is an autoimmune disease of the stomach characterized by the destruction of the oxyntic mucosa, which stops producing acid and becomes both functionally and morphologically atrophic. The pathogenic mechanisms behind the disease are still poorly understood. There is no early diagnosis and specific AIG therapy. To elucidate the pathogenesis of AIG, to search for early diagnostic markers, as well as to test new therapeutic approaches, an adequate and easily reproducible experimental model for autoimmune gastritis (EAG) is needed. Existing EAG models have some limitations, including slow development of signs, absence of advanced gastritis, irrational use of animals to obtain antigen. The aim was to find out whether it is possible to cause autoimmune gastritis similar to human disease in Wistar rats through immunization with a homologous gastric mucosa extract. Methods Wistar rats were immunized with gastric mucosa extract. Histology studies and evaluation of serological parameters were performed 56 and 91 days later. Results Destruction of oxyntic glands by infiltrating T lymphocytes were detected in rats on 56 and 91 days after initial immunization with gastric mucosa extract. Hyperplasia of enterochromaffin-like (ECL) cells was detected on the 91st day. Antral mucosa remained unchanged. Conclusion Wistar rats, immunized with gastric mucosa extract, developed EAG similar to human AIG. The advantages of received EAG model are the ease of obtaining, the rapid development of oxyntic mucosa damage, which may progress to ECL cell hyperplasia.

The protective effect of Aspalathus linearis against the experimental gastric ulcer induced by ethanol in rats

This study aimed to investigate the effect of Aspalathus linearis on the expression levels of major histocompatibility complex (MHC) molecules and their ability to present antigens to CD8, CD68, and T cells in an experimental rat model of gastritis. Furthermore, changes in tumor necrosis factor–alpha (TNF–α), myeloperoxidase, superoxide dismutase, and malondialdehyde levels due to the antioxidant properties of the plant were evaluated. The study included 24 female Wistar albino rats (Rattus norvegicus). A. linearis was administered to the treatment groups of an ethanol–induced gastritis rat model via oral gavage for 5 days the blood and stomach tissues were sampled for analysis. Biochemical evaluation revealed that TNF–α and myeloperoxidase levels decreased and superoxide dismutase activity increased in the A. linearis–treated groups compared with the ethanol–treated group. Histochemical evaluation revealed that the severity of inflammation decreased in the rats with gastritis treated with A. linearis. In addition, the number of cells expressing CD8 and CD68 decreased. The number of MHC–II immunopositive cells was higher in the A. linearis–treated group compared with the control and other treatment groups. A. linearis exhibits a protective effect on gastric mucosa by reducing the severity of oxidative stress owing to its antioxidant, anti–inflammatory, and antiapopitotic properties.

Treatment with IgG Fc fragments bearing regRF epitopes prevents destruction of the gastric mucosa in experimental autoimmune gastritis model

Autoimmune gastritis (AIG) is the autoimmune disease of the stomach characterized by the destruction of the oxyntic mucosa, which stops producing acid and becomes both functionally and morphologically atrophic. There is no specific treatment for AIG. Previously, we identified a new immunoregulatory factor (regulatory rheumatoid factor (regRF)), the stimulation production of which reduces certain experimental autoimmune diseases. Epitopes specific to the regulatory rheumatoid factor (regRF epitopes) can be obtained on IgG Fc fragments. In the rat AIG model, the therapeutic efficacy of IgG Fc fragments bearing regRF epitopes was tested. Treatment with IgG Fc fragments bearing regRF epitopes reduced T lymphocytic infiltration of oxyntic mucosa and prevented its damage in the AIG rat model, while in rats treated with placebo, T lymphocytic infiltration of the mucosa, loss of parietal cells, including severe were observed. Therefore, IgG Fc fragments bearing regRF epitopes are a potential therapeutic agent for treating autoimmune gastritis in its early stages.

Identification of the therapeutic effect and molecular mechanism of Coptis chinensis Franch. and Magnolia officinalis var. biloba on chronic gastritis

Ethnopharmacological relevanceTraditional Chinese medicine (TCM) theory believes that clearing heat and promoting dampness is the main treatment method for chronic gastritis. Coptis chinensis Franch. has the effects of clearing heat, detoxifying, and anti-inflammatory; Magnolia officinalis var. biloba can be used to treat abdominal pain, cough, and asthma. Coptis chinensis Franch. and Magnolia officinalis var. biloba can regulate the balance of intestinal microbiota and inhibit inflammatory reactions. AimThis study will verify the therapeutic effect of Coptis chinensis Franch. and Magnolia officinalis var. biloba on chronic gastritis, and explore its mechanism through transcriptome sequencing. MethodsFirstly, a rat chronic gastritis model was established, and the anal temperature and body weight changes of the rats before and after modeling were observed. Next, H&E staining, TUNEL assay and ELISA assay were performed on rat gastric mucosal tissues. Subsequently, the key fractions of Coptis chinensis Franch. and Magnolia officinalis var. biloba were obtained by high performance liquid chromatography (HPLC), and a GES-1 cell inflammation model was constructed to select the optimal monomer. Finally, the mechanism of action of Coptis chinensis Franch. and Magnolia officinalis var. biloba was explored through RNA seq. ResultsCompared with the control group, the rats in the administered group were in better condition, with higher anal temperature, reduced inflammatory response in gastric mucosal tissue and reduced apoptosis. The optimal fraction Coptisine was subsequently determined by HPLC and GES-1 cell model. RNA-seq analysis revealed that DEG was significantly enriched in ribosomes, NF-κB signaling pathway, etc. The key genes TPT1 and RPL37 were subsequently obtained. ConclusionsThis study verified the therapeutic effects of Coptis chinensis Franch. and Magnolia officinalis var. biloba on chronic gastritis by in vivo and in vitro experiments in rats, identified Coptisine as the optimal component, and obtained two potential target genes.

BanXiaXieXin decoction treating gastritis mice with drug-resistant Helicobacter pylori and its mechanism.

Helicobacter pylori (H. pylori) is the main pathogen that causes a variety of upper digestive diseases. The drug resistance rate of H. pylori is increasingly higher, and the eradication rate is increasingly lower. The antimicrobial resistance of H. pylori is an urgent global problem. It has been confirmed that Banxia Xiexin decoction (BXXXT) demonstrates the effects of treating gastrointestinal diseases, inhibiting H. pylori and protecting gastric mucosa. The purpose of the present study is to further explore the therapeutic effects of BXXXT on drug-resistant H. pylori. To confirm that BXXXT demonstrates therapeutical effects in vivo and in vitro on gastritis mice with drug-resistant H. pylori and explain its mechanism to provide an experimental basis for promoting the application of BXXXT. The aqueous extract of BXXXT was gained by water decocting method. The inhibitory effect of the aqueous extract on H. pylori was detected by dilution in vitro; drug-resistant H. pylori cells were used to build an acute gastritis model in vivo. Thereafter, the model mice were treated with the aqueous extract of BXXXT. The amount of H. pylori colonization, the repair of gastric mucosal damage, changes of inflammatory factors, apoptosis, etc., were assessed. In terms of mechanism exploration, the main medicinal compositions of BXXXT aqueous extract and the synergistic bacteriostatic effects they had demonstrated were analyzed using mass spectrometry; the immune function of peripheral blood cells such as CD3+ T and CD4+ T of mice with gastritis before and after treatment with BXXXT aqueous extract was detected using a flow cytometry; the H. pylori transcriptome and proteome after treatment with BXXXT aqueous extract were detected. Differently expressed genes were screened and verification was performed thereon with knockout expression. The minimum inhibitory concentration of BXXXT aqueous extract against H. pylori was 256-512 μg/mL. A dose of 28 mg/kg BXXXT aqueous extract treatment produced better therapeutical effects than the standard triple therapy did; the BXXXT aqueous extract have at least 11 ingredients inhibiting H. pylori, including berberine, quercetin, baicalin, luteolin, gallic acid, rosmarinic acid, aloe emodin, etc., of which berberine, aloe emodin, luteolin and gallic acid have a synergistic effect; BXXXT aqueous extract was found to stimulate the expressions of CD3+ T and CD4+ T and increase the number of CD4+ T/CD8+ T in gastritis mice; the detection of transcriptome and proteome, quantitative polymerase chain reaction, Western blotting and knockout verification revealed that the main targets of BXXXT aqueous extract are CFAs related to urea enzymes, and CagA, VacA, etc. BXXXT aqueous extract could demonstrate good therapeutic effects on drug-resistance H. pylori in vitro and in vivo and its mechanism comes down to the synergistic or additional antibacterial effects of berberine, emodin and luteolin, the main components of the extract; the extract could activate the immune function and enhance bactericidal effects; BXXXT aqueous extract, with main targets of BXXXT aqueous extract related to urease, virulence factors, etc., could reduce the urease and virulence of H. pylori, weaken its colonization, and reduce its inflammatory damage to the gastric mucosa.

Feasibility of mixed herbal medicine for improving gastric function in an alcohol-induced gastritis model.

Excessive exercise causes various gastric dysfunction. Gastritis is common among athletes who perform high-intensity training. Gastritis is a digestive disease involving mucosal damage caused by inflammatory reactions and oxidative stress. In this study, the effects of a complex natural extract on gastric mucosal damage and the expression of inflammatory factors were evaluated in an animal model of alcohol-induced gastritis. A mixed herbal medicine (Ma-al-gan; MAG) was prepared with four natural products (Curcumae longae Rhizoma, Schisandrae chinensis Fructus, Artemisiae scopariae herba, and Gardeniae Fructus) identified by a systemic analysis using the Traditional Chinese Medicine Systems Pharmacology platform. The effects of MAG on alcohol-induced gastric damage were evaluated. MAG (10-100 μg/mL) significantly reduced the mRNA and protein levels of inducible nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide-stimulated RAW264.7 cells. MAG (500 mg/kg/d) effectively prevented alcohol-induced gastric mucosal injury in vivo. MAG regulates inflammatory signals and oxidative stress and is a potential herbal medicine for gastric disorders.

Artificial intelligence-guided discovery of gastric cancer continuum

BackgroundDetailed understanding of pre-, early and late neoplastic states in gastric cancer helps develop better models of risk of progression to gastric cancers (GCs) and medical treatment to intercept such progression.MethodsWe built a Boolean implication network of gastric cancer and deployed machine learning algorithms to develop predictive models of known pre-neoplastic states, e.g., atrophic gastritis, intestinal metaplasia (IM) and low- to high-grade intestinal neoplasia (L/HGIN), and GC. Our approach exploits the presence of asymmetric Boolean implication relationships that are likely to be invariant across almost all gastric cancer datasets. Invariant asymmetric Boolean implication relationships can decipher fundamental time-series underlying the biological data. Pursuing this method, we developed a healthy mucosa → GC continuum model based on this approach.ResultsOur model performed better against publicly available models for distinguishing healthy versus GC samples. Although not trained on IM and L/HGIN datasets, the model could identify the risk of progression to GC via the metaplasia → dysplasia → neoplasia cascade in patient samples. The model could rank all publicly available mouse models for their ability to best recapitulate the gene expression patterns during human GC initiation and progression.ConclusionsA Boolean implication network enabled the identification of hitherto undefined continuum states during GC initiation. The developed model could now serve as a starting point for rationalizing candidate therapeutic targets to intercept GC progression.

Weikangling capsules combined with omeprazole ameliorates ethanol-induced chronic gastritis by regulating gut microbiota and EGF-EGFR-ERK pathway

AimsWeikangling capsules (WKLCs) have been widely used in the treatment of chronic gastritis. Whether used alone or combined with omeprazole (OME), it shows a significant effect. However, the mechanisms haven't been established. The study aimed to explore the mechanisms of WKLCs and its combination with OME on chronic gastritis. Main methodsThe components of WKLCs and EA (the ethyl acetate extraction extracted from WKLCs) fraction were analyzed. Then chronic gastritis model rats were induced by 56 % ethanol and treated with OME, low dose of WKLCs (WKL), high dose of WKLCs (WKH), WKLCs combined with OME (WO), and EA fraction (EA) to evaluate the mechanisms of WKLCs, drug combination and EA fraction. Key findingsA total of 22 components of WKLCs were quantified, among them 18 were enriched in EA fraction. WKLCs alleviated the morphology and inflammation of gastric mucosa and downregulated the levels of inflammatory factors (IL-1β, TNF-α, IL-6) and epidermal growth factor (EGF) in serum by inhibiting the EGF-EGFR-ERK pathway, regulating gut microbiota composition and SCFAs contents in feces. WKLCs plus OME was better than OME. EA fraction improved digestive function by increasing pepsin activity and decreasing gastrointestinal hormones (GAS and VIP) compared with WKLCs. SignificanceThis study elucidated that the effect of WKLCs and its combination with OME in the treatment of chronic gastritis was attributed to regulating the composition of the gut microbiota and inhibiting the EGF-EGFR-ERK pathway. The EA fraction is an inseparable effective substance of WKLCs. This study provides scientific evidence for clinical application.

Dangshen Huangjiu prevents gastric mucosal injury and inhibits Akt/NF-κB pathway.

One of the top ten tonic herbs, Dangshen is frequently found in Chinese functional foods. With the inclusion of Dangshen in the list of food and medicine substances in 2020, the Dangshen Huangjiu (DHJ) emerged. In the Bencao, it is written that Huangjiu can "open up the curved veins and thicken the stomach and intestines". Furthermore, increasing investigations have verified the protective effect of Dangshen on the gastric mucosa. Therefore, we propose the hypothesis that the stomach mucosa might be protected by the DHJ. To demonstrate that the effect of solids in Dangshen Huangjiu (DHJG) on damaged human gastric mucosal epithelial cells (GES-1) was reversed, the study used ethanol to induce injury to GES-1 and then used protein immunoblotting (western blotting) to determine the expression levels of p-Akt, p-NF-κB-p65, and NF-κB-p65 proteins in the cells. 0.04 mol L-1 MNNG (5 mL kg-1 body weight) mixed with eating disorders(2 d satiety, l d starvation, 3 d cycle) was used to further establish a chronic non-atrophic gastritis (CNAG) model in Wistar rats, at the same time, the experimental rats were given DHJ and DHJG gavage. Cellular assays confirmed that DHJG (25-100 μg mL-1) dose-dependently increased the viability of ethanol-injured GES-1 and lowered p-Akt and p-NF-κB-p65/NF-κB-p65 protein expression. Animal experiments revealed that 10 mL kg-1 and 20 mL kg-1 DHJ had no significant effect on the basic activity and gastric tissues and related biochemical indices of healthy rats; DHJ (10 mL kg-1, 20 mL kg-1) and DHJG (2.8 g kg-1, 11.4 g kg-1) resulted in some improvement in weight loss and significant improvement in gastric mucosal pathology in CNAG rats with damage. Particularly, DHJ and DHJG significantly decreased the expression of p-Akt, p-NF-κB-p65/NF-κB-p65 and Bcl-2/Bax proteins and Akt, IKKβ, IκBα and NF-κB mRNA in the gastric tissues of CNAG rats. These results showed that DHJG ameliorates ethanol-induced GES-1 cell injury; both DHJ and DHJG alleviate CNAG, and the mechanisms by which they do so may be related to DHJ and DHJG increasing the antioxidant capacity (elevating SOD, decreasing MDA), attenuating inflammatory responses (decreasing IL-1β, IL-6, and TNF-α), reversing apoptosis (reducing the Bcl-2/Bax ratio) and down-regulating gastric tissue p-Akt and p-NF-κB-p65/NF-κB-p65 protein expression as well as Akt, IKKβ, IκBα and NF-κB mRNA expression. This study indicates that the interventional effects of DHJ and DHJG in CNAG may act through the Akt/NF-κB signaling pathway.

Guettarda crispiflora Vahl Methanol Extract Ameliorates Acute Lung Injury and Gastritis by Suppressing Src Phosphorylation.

Many species in the genus Guettarda are known to exert anti-inflammatory effects and are used as traditional medicinal plants to treat various inflammatory symptoms. However, no studies on the inflammatory activities of Guettarda crispiflora Vahl have been reported. The aim of the study was to investigate in vitro and in vivo the anti-inflammatory effects of a methanol extract of Guettarda crispiflora Vahl (Gc-ME). To determine the anti-inflammatory activity of Gc-ME, lipopolysaccharide (LPS)-, poly(I:C)-, or Pam3CSK4-treated RAW264.7 cells, HCl/EtOH- and LPS-treated mice were employed for in vitro and in vivo tests. LPS-induced nitric oxide production in RAW264.7 cells was determined by Griess assays and cytokine gene expression in LPS-activated RAW264.7 cells, confirmed by RT- and real-time PCR. Transcriptional activation was evaluated by luciferase reporter gene assay. Target protein validation was assessed by Western blot analysis and cellular thermal shift assays (CETSA) with LPS-treated RAW264.7 and gene-transfected HEK293 cells. Using both a HCl/EtOH-induced gastritis model and an LPS-induced lung injury model, inflammatory states were checked by scoring or evaluating gastric lesions, lung edema, and lung histology. Phytochemical fingerprinting of Gc-ME was observed by using liquid chromatography-mass spectrometry. Nitric oxide production induced by LPS and Pam3CSK4 in RAW264.7 cells was revealed to be reduced by Gc-ME. The LPS-induced upregulation of iNOS, COX-2, IL-6, and IL-1β was also suppressed by Gc-ME treatment. Gc-ME downregulated the promotor activities of AP-1 and NF-κB triggered by MyD88- and TRIF induction. Upstream signaling proteins for NF-κB activation, namely, p-p50, p-p65, p-IκBα, and p-Src were all downregulated by Ch-EE. Moreover, Src was revealed to be directly targeted by Gc-ME. This extract, orally treated strongly, attenuated the inflammatory symptoms in HCl/EtOH-treated stomachs and LPS-treated lungs. Therefore, these results strongly imply that Guettarda crispiflora can be developed as a promising anti-inflammatory remedy with Src-suppressive properties.

Coptis, Pinellia, and Scutellaria as a promising new drug combination for treatment of Helicobacter pylori infection.

Helicobacter pylori (H. pylori) is the most important infectious agent and plays an important role in the progression of chronic gastritis and the development of gastric cancer. To identify efficient therapeutic agents or strategies that can treat H. pylori infection. We performed literature analysis, experimental validation, and network pharmacology. First, traditional Chinese medicine (TCM) prescriptions for the treatment of H. pylori infection were obtained from the China National Knowledge Infrastructure, China Biology Medicine, China Science and Technology Journal Database, and WanFang databases. In addition, we conducted a relevant search by Reference Citation Analysis (RCA) (https://www.referencecitationanalysis.com). Next, we used TCM Inheritance Support System V2.5 to identify core drug combinations in the TCM prescriptions. Then, an H. pylori-associated chronic mouse model of gastritis was established. The antibacterial properties and anti-inflammatory potential of the core drug combination were evaluated by the rapid urease test, modified Warthin-Starry silver staining, histopathological analysis, and enzyme linked immunosorbent assay. Finally, the active compounds, hub targets, and potential signaling pathways associated with the core drug combination were analyzed by network pharmacology. The TCM treatment of H. pylori was mainly based on reinforcing the healthy Qi and eliminating pathogenic factors by simultaneously applying pungent dispersing, bitter descending, cold and warm drugs. The combination of Coptis, Pinellia, and Scutellaria (CPS) was identified as the core drug combination from 207 prescriptions and 168 herbs. This drug combination eradicated H. pylori, alleviated the gastric pathology induced by H. pylori infection, and reduced the expression levels of tumor necrosis factor-α (P = 0.024) and interleukin-1β (P = 0.001). Moreover, a total of 35 compounds and 2807 targets of CPS were identified using online databases. Nine key compounds (tenaxin I, neobaicalein, norwogonin, skullcapflavone II, baicalein, 5,8,2'-trihydroxy-7-methoxyflavone, acacetin, panicolin, and wogonin) and nine hub target proteins (EGFR, PTGS2, STAT3, MAPK3, MAPK8, HSP90AA1, MAPK1, MMP9, and MTOR) were further explored. Seventy-seven signaling pathways were correlated with H. pylori-induced inflammation and carcinogenesis. In summary, we showed that CPS is the core drug combination for treating H. pylori infection. Animal experiments demonstrated that CPS has bacteriostatic properties and can reduce the release of inflammatory cytokines in the gastric mucosa. Network pharmacology predictions further revealed that CPS showed complex chemical compositions with multi-target and multi-pathway regulatory mechanisms. Although the results derived from network pharmacology are not necessarily comprehensive, they still expand our understanding of CPS for treating H. pylori infection.