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Xiao-Jian-Zhong-Tang (XJZT) has the effect of warming the middle and tonifying the deficiency, easing the urgency and relieving pain according to the theory of traditional Chinese medicine (TCM), and is able to treat spleen deficiency type chronic atrophic gastritis (CAG). Metabolites of TCM in cecum contents are common metabolites of intestinal bacteria and hosts, which can reflect the metabolic status in disease states. The present work was performed to study the effect of XJZT against CAG coupled with the cecal metabolites analysis and bioinformatics. A total of nine prototypical components and 144 metabolites were firstly identified in the cecum metabolites of XJZT using ultra-high performance liquid chromatography added to the quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF/MS), which underwent the metabolism of oxidation, reduction, methylation, and glucuronic acid reaction Furthermore, different prototypical compounds might metabolize into identical metabolites in the presence of intestinal flora. Bioinformatics was further used to correlate these metabolites with the disease and intestinal flora. Components and targets were screened by Cytoscape, and molecular docking of key targets and core components showed good binding ability. This study provided important information for exploring the mechanism of TCM formulae.

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Chronic atrophic gastritis (CAG) is a critical initial step in gastric cancer tumorigenesis accompanied by high malignancy. Erianin has been proposed as a promising agent in treating precancerous lesions of gastric cancer. Considering that little work has been implemented concerning the specific role and possible regulatory mechanism of Erianin in CAG, the goal of the study is to disclose the effects and mechanism of erianin on the malignant transformation in the process of CAG. CAG cell model was generated in human gastric epithelium GES-1 cells induced by Nmethyl-N'-nitro-N-nitrosoguanidine (MNNG). CCK-8 method determined cell viability. ELISA and corresponding assay kits severally appraised the contents of inflammatory cytokines and oxidative stress markers. Cellular reactive oxygen species (ROS) formation was measured by flow cytometry analysis using DCFH-DA probe. GFP-LC3 immunofluorescence staining and Western blotting evaluated autophagy. Also, Western blotting analyzed the expression of components in mitogen activated protein kinase (MAPK)/mechanistic target of rapamycin (mTOR) signaling. The results manifested that MNNG treatment diminished the viability and autophagy whereas intensified the inflammation and oxidative stress in GES-1 cells, which were all reversed by Erianin. Besides, Erianin blocked mTOR/MAPK signaling in MNNG-exposed GES-1 cells. Autophagy inhibitor 3-methyladenine (3-MA) or p38 MAPK agonist asiatic acid partially counteracted the protection elicited by Erianin against viability loss, inflammatory reaction as well as oxidative stress in MNNG-induced GES-1 cells. Combined with the findings, Erianin might mediate autophagy to improve MNNG-elicited CAG via MAPK/mTOR signaling.

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Background and Aims：Chronic atrophic gastritis (CAG) is an important precursor of gastric cancer(GC), and there is currently a lack of reliable non-invasive diagnostic markers. This study aims to find a biomarker for non-invasive screening of CAG in the community. Methods: A total of 540 individuals were enrolled (test set = 385, validation set = 155). ROC curve analysis was used to evaluate the diagnostic significance of Trefoil Factor 3(TFF3) alone or in combination with pepsinogen (PG) for CAG in test and validation set. Furthermore, the diagnostic value of TFF3 and PG in different H. pylori infection states was studied. Results：When compared with the chronic superficial gastritis (CSG), the expression level of TFF3 in the CAG was higher (27ng/ml VS 19.61, P < 0.001). ROC curve analysis found that the sensitivity, specificity, and area under the curve (AUC) of CAG diagnosis using serum TFF3 alone at the optimal cut-off value of 26.55ng/ml were 0.529, 0.87, and 0.739, respectively. When TFF3 was combined with The Ratio of PGI to PGII (PGR), the AUC and specificity reached to 0.755 and 0.825 respectively. TFF3 individual or combined with PGR had good predictive value especially in the H. Pylori negative patients. Conclusion: TFF3 combined with PGR can effectively predict CAG especially in the patients with H. pylori negative.

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ETHNOPHARMACOLOGICAL RELEVANCE: Chronic atrophic gastritis (CAG), precancerous lesions of gastric cancer (PLGC), and gastric cancer (GC), seriously threaten human health. Traditional Chinese medicine (TCM) has been employed in the treatment of chronic diseases for a long time and has shown remarkable efficacy. AIM OF THE STUDY: Recently, there has been an increasing use of TCM in treating CAG, PLGC, and GC. The objective of this study is to compile a comprehensive overview of the existing research on the effects and molecular mechanisms of TCM, including formulas, single herbs, and active components. MATERIALS AND METHODS: To obtain a comprehensive understanding of traditional use of TCM in treating these diseases, we reviewed ancient books and Chinese literature. In addition, keywords such as "TCM", "CAG", "PLGC", "GC", and "active ingredients" were used to collect modern research on TCM published in databases such as CNKI, Web of Science, and Pubmed up to April 2024. All collected information was then summarized and analyzed. RESULTS: This study analyzed 174 articles, which covered the research progress of 20 TCM formulas, 14 single herbs, and 50 active ingredients in treating CAG, PLGC, and GC. Sources, effects, and molecular mechanisms of the TCM were summarized. CONCLUSIONS: This article reviews the progress of TCM in the management of CAG, PLGC, and GC, which will provide a foundation for the clinical application and further development of TCM.

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Chronic atrophic gastritis (CAG) is a prevalent preneoplastic condition of the stomach. Palmatine (PAL), an isoquinoline alkaloid isolated from Rhizoma Coptidis (RC), has significant anti-inflammatory properties and is often used to treat gastrointestinal disorders. However, the mechanism of PAL on CAG remains unclear. In this study, N-methyl-N'-nitrosoguanidine (MNNG) was used to induce CAG inflammatory disease models in vivo and in vitro. The efficacy of five alkaloids in RC and the dose-dependent effects of the most effective PAL in CAG mice were evaluated in two animal experiments. RNA-seq and western blot revealed that PAL significantly improved IL-17, TNF, and NF-kappa B inflammation-related signaling pathways. Further hub gene prediction and experimental validation revealed that PAL modulated the STAT1/CXCL10 axis, thereby exerting attenuation of CAG through the regulation of IL-17, TNF-α, and p-p65 expression. In conclusion, PAL was proposed to mitigate MNNG-induced CAG, potentially through the inhibition of oxidative stress and inflammatory responses via the STAT1/CXCL10 axis. This approach is an effective complement to the use of PAL in the treatment of CAG.

Asunto(s)

Alcaloides de Berberina , Quimiocina CXCL10 , Gastritis Atrófica , Metilnitronitrosoguanidina , Factor de Transcripción STAT1 , Animales , Factor de Transcripción STAT1/metabolismo , Ratones , Gastritis Atrófica/tratamiento farmacológico , Gastritis Atrófica/metabolismo , Gastritis Atrófica/inducido químicamente , Metilnitronitrosoguanidina/toxicidad , Quimiocina CXCL10/metabolismo , Quimiocina CXCL10/genética , Masculino , Alcaloides de Berberina/farmacología , Transducción de Señal/efectos de los fármacos , Ratones Endogámicos C57BL , Interleucina-17/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Enfermedad Crónica

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Parietal cell autoantibodies (PCAs), which recognize the enzyme H+/K+-ATPase as a target, are considered to be a diagnostic marker of autoimmune gastritis and pernicious anemia; these conditions are characterized by the presence of corpus atrophic gastritis. Circulating PCAs can be detected using several analytical methods that are commonly available in the clinical laboratory. Traditionally, indirect immunofluorescence (IIF) on rodent or primate stomach tissue is used as a screening test for the detection of PCAs. However, IIF suffers from a high inter-observer variability and lacks standardization. In addition, like immunoblotting, results are expressed only in a qualitative or semi-quantitative manner. Based on the few available studies that are reviewed herein, quantitative enzyme-linked immunosorbent assays (ELISAs) and fluorescence enzyme immunoassays (FEIAs) using purified H+/K+-ATPase perform better than IIF in the detection of PCAs, displaying higher sensitivity and utility in monitoring the disease. In light of their higher diagnostic accuracy, these solid-phase methods should be preferred to IIF in the screening of autoimmune atrophic gastritis. The use of methods to detect antibodies versus a specific subunit of H+/K+-ATPase (α or ß) is currently confined to the world of research. Further investigation is required to define the clinical utility of H+/K+-ATPase subunit detection.

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ETHNOPHARMACOLOGICAL RELEVANCE: Characterized by inflammation of the gastric mucosa, atrophy of gastric gland cells, and intestinal metaplasia, Chronic Atrophic Gastritis (CAG) is a precancerous lesion disease. In traditional Chinese medicine, Rhizoma Coptidis (RC) is extensively used for treating gastrointestinal disorders, mainly because RC alkaloids-based extracts are the main active pharmaceutical ingredients. Total Rhizoma Coptidis extracts (TRCE) is a mixture of Rhizoma Coptidis extracts from Rhizoma Coptidis with alkaloids as the main components. However, the efficacy and mechanism of TRCE on CAG need further study. AIM OF THE STUDY: To explore the therapeutic effect and underlying mechanisms of action of TRCE on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced chronic atrophic gastritis (CAG) using network pharmacological analysis. MATERIALS AND METHODS: The amelioration effect of TRCE on CAG was evaluated in MNNG-induced CAG mice. The pathological severity of the mice was evaluated through H&E staining. Detection of gastric mucosal parietal cell loss was conducted using immunofluorescence staining, and serum indices were measured using ELISA. Additionally, the active compounds and drug targets of Rhizoma Coptidis were curated from the STP, SEA, and TCMSP databases, alongside disease targets of CAG sourced from PharmGkb, OMIM, and GeneCards databases. By mapping drug targets to disease targets, overlapping targets were identified. A shared protein-protein interaction (PPI) and drug target network were constructed for the overlapping targets and analyzed for KEGG enrichment. RESULTS: The results of animal experiments demonstrate that TRCE has the potential to improve the CAG process in mice. In conjunction with disease characteristics, cyberpharmacology analysis has identified nine core compounds, 151 targets, 10 core targets, and five significant inflammatory pathways within the compound-target-pathway network. Furthermore, there is a remarkable coincidence rate of 98% between the core compound targets of TRCE and the targets present in the CAG disease database. The accurate search and calculation of literature reports indicate that the coverage rate for 121 predicted core targets related to CAG reaches 81%. The primary characteristic of CAG lies in its inflammatory process. Both predicted and experimental findings confirm that TRCE can regulate ten key inflammation-associated targets (TP53, STAT3, AKT1, HSP90AA1, TNF, IL-6, MAPK3, SRC, JUN, and HSP90AA1) as well as inflammation-related pathways (MAPK, HIF-1, Toll-Like Receptor, IL-17, TNF, and other signaling pathways). These mechanisms mitigate inflammation and reduce gastric mucosal damage in CAG mice. CONCLUSIONS: In conclusion, TRCE was shown to alleviate CAG by modulating TP53, STAT3, AKT1, HSP90AA1, TNF, IL-6, MAPK3, SRC, JUN, and EGFR, as demonstrated by combined network pharmacology and biological experiments. In conclusion, our study provides a robust foundation for future clinical trials evaluating the efficacy of RC in treating CAG.

Asunto(s)

Medicamentos Herbarios Chinos , Gastritis Atrófica , Metilnitronitrosoguanidina , Animales , Gastritis Atrófica/tratamiento farmacológico , Gastritis Atrófica/inducido químicamente , Gastritis Atrófica/patología , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Ratones , Masculino , Farmacología en Red , Coptis chinensis , Mapas de Interacción de Proteínas , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Mucosa Gástrica/metabolismo , Enfermedad Crónica , Modelos Animales de Enfermedad

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BACKGROUND: The Chinese medicine Yangyin Huowei mixture (YYHWM) exhibits good clinical efficacy in the treatment of chronic atrophic gastritis (CAG), but the mechanisms underlying its activity remain unclear. AIM: To investigate the therapeutic effects of YYHWM and its underlying mechanisms in a CAG rat model. METHODS: Sprague-Dawley rats were allocated into control, model, vitacoenzyme, and low, medium, and high-dose YYHWM groups. CAG was induced in rats using N-methyl-N'-nitro-N-nitrosoguanidine, ranitidine hydrochloride, hunger and satiety perturbation, and ethanol gavage. Following an 8-wk intervention period, stomach samples were taken, stained, and examined for histopathological changes. ELISA was utilized to quantify serum levels of PG-I, PG-II, G-17, IL-1ß, IL-6, and TNF-α. Western blot analysis was performed to evaluate protein expression of IL-10, JAK1, and STAT3. RESULTS: The model group showed gastric mucosal layer disruption and inflammatory cell infiltration. Compared with the blank control group, serum levels of PGI, PGII, and G-17 in the model group were significantly reduced (82.41 ± 3.53 vs 38.52 ± 1.71, 23.06 ± 0.96 vs 11.06 ± 0.70, and 493.09 ± 12.17 vs 225.52 ± 17.44, P < 0.01 for all), whereas those of IL-1ß, IL-6, and TNF-α were significantly increased (30.15 ± 3.07 vs 80.98 ± 4.47, 69.05 ± 12.72 vs 110.85 ± 6.68, and 209.24 ± 11.62 vs 313.37 ± 36.77, P < 0.01 for all), and the protein levels of IL-10, JAK1, and STAT3 were higher in gastric mucosal tissues (0.47 ± 0.10 vs 1.11 ± 0.09, 0.49 ± 0.05 vs 0.99 ± 0.07, and 0.24 ± 0.05 vs 1.04 ± 0.14, P < 0.01 for all). Compared with the model group, high-dose YYHWM treatment significantly improved the gastric mucosal tissue damage, increased the levels of PGI, PGII, and G-17 (38.52 ± 1.71 vs 50.41 ± 3.53, 11.06 ± 0.70 vs 15.33 ± 1.24, and 225.52 ± 17.44 vs 329.22 ± 29.11, P < 0.01 for all), decreased the levels of IL-1ß, IL-6, and TNF-α (80.98 ± 4.47 vs 61.56 ± 4.02, 110.85 ± 6.68 vs 89.20 ± 8.48, and 313.37 ± 36.77 vs 267.30 ± 9.31, P < 0.01 for all), and evidently decreased the protein levels of IL-10 and STAT3 in gastric mucosal tissues (1.11 ± 0.09 vs 0.19 ± 0.07 and 1.04 ± 0.14 vs 0.55 ± 0.09, P < 0.01 for both). CONCLUSION: YYHWM reduces the release of inflammatory factors by inhibiting the IL-10/JAK1/STAT3 pathway, alleviating gastric mucosal damage, and enhancing gastric secretory function, thereby ameliorating CAG development and cancer transformation.

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Background and Objective: Chronic atrophic gastritis (CAG) is a complex chronic disease caused by multiple factors that frequently occurs disease in the clinic. The worldwide prevalence of CAG is high. Interestingly, clinical CAG patients often present with a variety of symptom phenotypes, which makes it more difficult for clinicians to treat. Therefore, there is an urgent need to improve our understanding of the complexity of the clinical CAG population, obtain more accurate disease subtypes, and explore the relationship between clinical symptoms and medication. Therefore, based on the integrated platform of complex networks and clinical research, we classified the collected patients with CAG according to their different clinical characteristics and conducted correlation analysis on the classification results to identify more accurate disease subtypes to aid in personalized clinical treatment. Method: Traditional Chinese medicine (TCM) offers an empirical understanding of the clinical subtypes of complicated disorders since TCM therapy is tailored to the patient's symptom profile. We gathered 6,253 TCM clinical electronic medical records (EMRs) from CAG patients and manually annotated, extracted, and preprocessed the data. A shared symptom-patient similarity network (PSN) was created. CAG patient subgroups were established, and their clinical features were determined through enrichment analysis employing community identification methods. Different clinical features of relevant subgroups were correlated based on effectiveness to identify symptom-botanical botanical drugs correspondence. Moreover, network pharmacology was employed to identify possible biological relationships between screened symptoms and medications and to identify various clinical and molecular aspects of the key subtypes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results: 5,132 patients were included in the study: 2,699 males (52.60%) and 2,433 females (47.41%). The population was divided into 176 modules. We selected the first 3 modules (M29, M3, and M0) to illustrate the characteristic phenotypes and genotypes of CAG disease subtypes. The M29 subgroup was characterized by gastric fullness disease and internal syndrome of turbidity and poison. The M3 subgroup was characterized by epigastric pain and disharmony between the liver and stomach. The M0 subgroup was characterized by epigastric pain and dampness-heat syndrome. In symptom analysis, The top symptoms for symptom improvement in all three subgroups were stomach pain, bloating, insomnia, poor appetite, and heartburn. However, the three groups were different. The M29 subgroup was more likely to have stomach distention, anorexia, and palpitations. Citrus medica, Solanum nigrum, Jiangcan, Shan ci mushrooms, and Dillon were the most popular botanical drugs. The M3 subgroup has a higher incidence of yellow urine, a bitter tongue, and stomachaches. Smilax glabra, Cyperus rotundus, Angelica sinensis, Conioselinum anthriscoides, and Paeonia lactiflora were the botanical drugs used. Vomiting, nausea, stomach pain, and appetite loss are common in the M0 subgroup. The primary medications are Scutellaria baicalensis, Smilax glabra, Picrorhiza kurroa, Lilium lancifolium, and Artemisia scoparia. Through GO and KEGG pathway analysis, We found that in the M29 subgroup, Citrus medica, Solanum nigrum, Jiangcan, Shan ci mushrooms, and Dillon may exert their therapeutic effects on the symptoms of gastric distension, anorexia, and palpitations by modulating apoptosis and NF-κB signaling pathways. In the M3 subgroup, Smilax glabra, Cyperus rotundus, Angelica sinensis, Conioselinum anthriscoides, and Paeonia lactiflora may be treated by NF-κB and JAK-STAT signaling pathway for the treatment of stomach pain, bitter mouth, and yellow urine. In the M0 subgroup, Scutellaria baicalensis, Smilax glabra, Picrorhiza kurroa, Lilium lancifolium, and Artemisia scoparia may exert their therapeutic effects on poor appetite, stomach pain, vomiting, and nausea through the PI3K-Akt signaling pathway. Conclusion: Based on PSN identification and community detection analysis, CAG population division can provide useful recommendations for clinical CAG treatment. This method is useful for CAG illness classification and genotyping investigations and can be used for other complicated chronic diseases.

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ETHNOPHARMACOLOGICAL RELEVANCE: Jianwei Xiaoyan Granule (JWXYG) is the traditional Chinese medicine preparation in Jiangyin Hospital Affiliated to Nanjing University of Chinese Medicine, which has been widely used in clinical treatment of chronic atrophic gastritis (CAG). However, the material basis and potential mechanism of JWXYG in the treatment of CAG are not clear. PURPOSE: To explore the material basis and potential mechanism of JWXYG in the treatment of CAG. METHODS: In this study, the components of JWXYG were analyzed by HPLC-Q-TOF-MS/MS. Then, the CAG model in rats established by a composite modeling method and MC cell model induced by MNNG were used to explore the improvement effect of JWXYG on CAG. Finally, the potential mechanism of JWXYG in the treatment of CAG was preliminarily predicted based on network pharmacology and validated experimentally. RESULTS: Thirty-one components of JWXYG were analyzed through HPLC-Q-TOF-MS/MS, such as albiflorin, paeoniflorin, lobetyolin firstly. Research results in vivo showed that the gastric mucosa became thinner, intestinal metaplasia appeared, the number of glands was reduced, the serum levels of PG I and PG II increased and the contents of G17 and IL-6 reduced in CAG model rats. After 4 weeks of JWXYG (2.70 g/kg) administration, these conditions were significantly improved. In addition, cell viability, migration, and invasion of MNNG-induced MC cells was inhibited by JWXYG treatment (800 µg/mL). Furthermore, the results of network pharmacology indicated that HIF-1 and VEGF signaling pathways might play important roles in the therapeutic process. Then the results of Western blot, immunohistochemistry and immunofluorescence confirmed that with JWXYG treatment, the increased expression of HIF-1α, VEGF and VEGFR2 in gastric issue of CAG rats were restrained. Eventually, potential components of JWXYG in the treatment of CAG were predicted through molecular docking to elucidate the material basis. CONCLUSION: JWXYG could inhibit angiogenesis by regulating HIF-1α-VEGF pathway to exert therapeutic effects on CAG. Our study explored the potential mechanisms and material basis of JWXYG in the treatment of CAG and provides experimental data for the clinical rational application of JWXYG.

Asunto(s)

Medicamentos Herbarios Chinos , Gastritis Atrófica , Subunidad alfa del Factor 1 Inducible por Hipoxia , Ratas Sprague-Dawley , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular , Animales , Gastritis Atrófica/tratamiento farmacológico , Gastritis Atrófica/patología , Gastritis Atrófica/metabolismo , Medicamentos Herbarios Chinos/farmacología , Masculino , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ratas , Transducción de Señal/efectos de los fármacos , Enfermedad Crónica , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Mucosa Gástrica/metabolismo , Modelos Animales de Enfermedad , Farmacología en Red

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BACKGROUND: Chronic atrophic gastritis (CAG) is a prevalent chronic gastritis usually accompanied by precancerous lesions such as intestinal metaplasia and dysplasia. The increasing application of traditional Chinese medicine in CAG treatment has shown promising results with low side effects and significant efficacy. AIM: To investigate the pharmacological effects of Yiqi Jiedu Huayu decoction (YJHD) on precancerous lesions of CAG. METHODS: A CAG rat model was established by Helicobacter pylori bacteria solution combined with N-methyl-N'-nitro-N-nitrosoguanidine. Histopathological measurements were conducted by hematoxylin-eosin and alcian blue and periodic acid-Schiff staining. Serum levels of inflammatory factors and gastric mucosal-related factors were examined using enzyme-linked immunosorbent assay. Protein and mRNA levels were quantified via western blot and quantitative real-time polymerase chain reaction analysis, respectively. Molecular interaction was verified by chromatin immunoprecipitation (ChIP) assay. RESULTS: YJHD greatly attenuated pathological changes in the gastric mucosa and precancerous lesions in CAG rats. Meanwhile, YJHD treatment reduced serum levels of inflammatory factors [interleukin (IL)-6, tumor necrosis factor-α and C-reactive protein] and increased serum levels of gastric mucosal-related factors (gastrin, pepsin, somatostatin and prostaglandin E2) in CAG rats. In addition, YJHD administration suppressed NLRP3 inflammasome-mediated cell pyroptosis, as well as the activation of TLR4/NF-κB and IL-6/STAT3 signaling pathways. Mechanically, ChIP experiments confirmed that NLRP3 transcription was regulated by TLR4/NF-κB and IL-6/STAT3 signaling. CONCLUSION: Taken together, YJHD alleviated NLRP3 inflammasome formation and pyroptosis of epithelial cells in CAG, potentially through the inactivation of TLR4/NF-κB and IL-6/STAT3 pathways.

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The present study aimed to explore the underlying mechanism of bile reflux-inducing chronic atrophic gastritis (CAG) with colonic mucosal lesion. The rat model of CAG with colonic mucosal lesion was induced by free-drinking 20 mmol/L sodium deoxycholate to simulate bile reflux and 2% cold sodium salicylate for 12 weeks. In comparison to the control group, the model rats had increased abundances of Bacteroidetes and Firmicutes but had decreased abundances of Proteobacteria and Fusobacterium. Several gut bacteria with bile acids transformation ability were enriched in the model group, such as Blautia, Phascolarctobacter, and Enterococcus. The cytotoxic deoxycholic acid and lithocholic acid were significantly increased in the model group. Transcriptome analysis of colonic tissues presented that the down-regulated genes enriched in T cell receptor signaling pathway, antigen processing and presentation, Th17 cell differentiation, Th1 and Th2 cell differentiation, and intestinal immune network for IgA production in the model group. These results suggest that bile reflux-inducing CAG with colonic mucosal lesion accompanied by gut dysbacteriosis, mucosal immunocompromise, and increased gene expressions related to repair of intestinal mucosal injury.

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Colon , Ácido Desoxicólico , Gastritis Atrófica , Microbioma Gastrointestinal , Mucosa Intestinal , Animales , Gastritis Atrófica/microbiología , Gastritis Atrófica/inmunología , Gastritis Atrófica/patología , Gastritis Atrófica/inducido químicamente , Ratas , Mucosa Intestinal/patología , Mucosa Intestinal/inmunología , Mucosa Intestinal/microbiología , Mucosa Intestinal/efectos de los fármacos , Masculino , Colon/patología , Colon/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Modelos Animales de Enfermedad , Inmunidad Mucosa/efectos de los fármacos , Ratas Sprague-Dawley , Enfermedad Crónica

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Chronic atrophic gastritis (CAG) is a chronic inflammatory disease and precancerous lesion in stomach cancer. Abnormal activation cellular ferroptosis further damages gastric tissue, which is susceptible to inflammation. Luteolin has powerful anti-inflammatory and regulatory potential for cellular ferroptosis. We aimed to clarify the involvement of luteolin in inflammation and ferroptosis during CAG. Luteolin targets were searched to identify intersecting genes in the chronic atrophic gastritis disease database. The AGE-RAGE pathway is a potential target of luteolin for the treatment of chronic atrophic gastritis and a binding site between luteolin and RAGE was predicted through a computer simulation of molecular docking. We established a CAG rat model using N-methyl-N-nitro-N-nitroguanidine. The therapeutic effect of luteolin on CAG was detected using western blotting, qPCR, hematoxylin and eosin staining, lipid oxidation (MDA), and Fe2+ assays. Luteolin inhibited the AGE-RAGE signaling pathway and reduced the inflammatory response in gastric tissues. Additionally, luteolin downregulated the concentration of (MDA) and Fe2+, and CAG downregulated the expression levels of ACSL4 and NOX1 and upregulated the expression levels of FIH1 and GPX4 ferroptosis-related proteins, thus inhibiting the ferroptosis of gastric tissue cells, which had a therapeutic effect on CAG.

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Ferroptosis , Gastritis Atrófica , Luteolina , Transducción de Señal , Ferroptosis/efectos de los fármacos , Luteolina/farmacología , Luteolina/uso terapéutico , Animales , Gastritis Atrófica/tratamiento farmacológico , Gastritis Atrófica/metabolismo , Gastritis Atrófica/patología , Gastritis Atrófica/genética , Ratas , Transducción de Señal/efectos de los fármacos , Masculino , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Receptor para Productos Finales de Glicación Avanzada/genética , Inflamación/metabolismo , Inflamación/tratamiento farmacológico , Productos Finales de Glicación Avanzada/metabolismo , Modelos Animales de Enfermedad , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Ratas Sprague-Dawley , Enfermedad Crónica , Simulación del Acoplamiento Molecular , Humanos , Antiinflamatorios/farmacología

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Gastric cancer (GC) is still one of the most prevalent cancers worldwide, with a high mortality rate, despite improvements in diagnostic and therapeutic strategies. To diminish the GC burden, a modification of the current diagnostic paradigm, and especially endoscopic diagnosis of symptomatic individuals, is necessary. In this review article, we present a broad review and the current knowledge status on serum biomarkers, including pepsinogens, gastrin, Gastropanel®, autoantibodies, and novel biomarkers, allowing us to estimate the risk of gastric precancerous conditions (GPC)-atrophic gastritis and gastric intestinal metaplasia. The aim of the article is to emphasize the role of non-invasive testing in GC prevention. This comprehensive review describes the pathophysiological background of investigated biomarkers, their status and performance based on available data, as well as their clinical applicability. We point out future perspectives of non-invasive testing and possible new biomarkers opportunities.

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BACKGROUND: Chronic atrophic gastritis (CAG) is a global digestive system disease and one of the important causes of gastric cancer. The incidence of CAG has been increasing yearly worldwide. PURPOSE: This article reviews the latest research on the common causes and future therapeutic targets of CAG as well as the pharmacological effects of corresponding clinical drugs. We provide a detailed theoretical basis for further research on possible methods for the treatment of CAG and reversal of the CAG process. RESULTS: CAG often develops from chronic gastritis, and its main pathological manifestation is atrophy of the gastric mucosa, which can develop into gastric cancer. The drug treatment of CAG can be divided into agents that regulate gastric acid secretion, eradicate Helicobacter. pylori (H. pylori), protect gastric mucous membrane, or inhibit inflammatory factors according to their mechanism of action. Although there are limited specific drugs for the treatment of CAG, progress is being made in defining the pathogenesis and therapeutic targets of the disease. Growing evidence shows that NF-κB, PI3K/AKT, Wnt/ ß-catenin, MAPK, Toll-like receptors (TLRs), Hedgehog, and VEGF signaling pathways play an important role in the development of CAG.

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Gastritis Atrófica , Transducción de Señal , Humanos , Gastritis Atrófica/tratamiento farmacológico , Gastritis Atrófica/microbiología , Gastritis Atrófica/patología , Gastritis Atrófica/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Enfermedad Crónica , Helicobacter pylori/efectos de los fármacos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiología

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Chronic atrophic gastritis (CAG), characterized by inflammation and erosion of the gastric lining, is a prevalent digestive disorder and considered a precursor to gastric cancer (GC). Coptis chinensis France (CCF) is renowned for its potent heat-clearing, detoxification, and anti-inflammatory properties. Zuojin Pill (ZJP), a classic Chinese medicine primarily composed of CCF, has demonstrated effectiveness in CAG treatment. This study aims to elucidate the potential mechanism of CCF treatment for CAG through a multifaceted approach encompassing network pharmacology, molecular docking, molecular dynamics simulation and experimental verification. The study identified three major active compounds of CCF and elucidated key pathways, such as TNF signaling, PI3K-Akt signaling and p53 signaling. Molecular docking revealed interactions between these active compounds and pivotal targets like PTGS2, TNF, MTOR, and TP53. Additionally, molecular dynamics simulation validated berberine as the primary active compound of CCF, which was further confirmed through experimental verification. This study not only identified berberine as the primary active compound of CCF but also provided valuable insights into the molecular mechanisms underlying CCF's efficacy in treating CAG. Furthermore, it offers a reference for refining therapeutic strategies for CAG management.

Asunto(s)

Coptis , Medicamentos Herbarios Chinos , Gastritis Atrófica , Simulación de Dinámica Molecular , Farmacología en Red , Humanos , Coptis/química , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/farmacología , Gastritis Atrófica/tratamiento farmacológico , Gastritis Atrófica/metabolismo , Simulación del Acoplamiento Molecular , Transducción de Señal/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismo , Berberina/química , Berberina/uso terapéutico , Berberina/farmacología , Factor de Necrosis Tumoral alfa/metabolismo

RESUMEN

Chronic atrophic gastritis (CAG) is characterized by the loss of gastric glandular cells, which are replaced by the intestinal-type epithelium and fibrous tissue. Ginsenoside Rg1 (Rg1) is the prevalent ginsenoside in ginseng, with a variety of biological activities, and is usually added to functional foods. As a novel form of programmed cell death (PCD), pyroptosis has received substantial attention in recent years. Despite the numerous beneficial effects, the curative impact of Rg1 on CAG and whether its putative mechanism is partially via inhibiting pyroptosis still remain unknown. To address this gap, we conducted a study to explore the mechanisms underlying the potential anti-CAG effect of Rg1. We constructed a CAG rat model using a multifactor comprehensive method. A cellular model was developed by using 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) combined with Nigericin as a stimulus applied to GES-1 cells. After Rg1 intervention, the levels of inflammatory indicators in the gastric tissue/cell supernatant were reduced. Rg1 relieved oxidative stress via reducing the myeloperoxidase (MPO) and malonaldehyde (MDA) levels in the gastric tissue and increasing the level of superoxide dismutase (SOD). Additionally, Rg1 improved MNNG+Nigericin-induced pyroptosis in the morphology and plasma membrane of the cells. Further research supported novel evidence for Rg1 in the regulation of the NF-κB/NLRP3/GSDMD pathway and the resulting pyroptosis underlying its therapeutic effect. Moreover, by overexpression and knockout of GSDMD in GES-1 cells, our findings suggested that GSDMD might serve as the key target in the effect of Rg1 on suppressing pyroptosis. All of these offer a potential theoretical foundation for applying Rg1 in ameliorating CAG.

RESUMEN

This research attempted to clarify the clinical diagnostic value of combined detection of gastric function and Helicobacter pylori (Hp) serotyping in chronic gastritis and gastric cancer (GC). The 80 chronic non atrophic gastritis (CNAG) patients treated in our hospital from October 2021 to October 2022 received selection as the CNAG group. The 96 chronic atrophic gastritis (CAG) patients diagnosed by gastroscopy and pathology in the same period received selection as CAG group. During the same period, 50 patients diagnosed with GC received inclusion in GC group. Pepsin I (PG I), PG II (PG II), gastrin-17 (G-17) and Hp serotyping received detection and comparison in three groups. The diagnostic efficacy of PG Ⅰ, PG Ⅱ, G-17, the ratio of serum PG I to PG II (PGR), and Hp serotyping in chronic gastritis and GC received evaluation by receiver operating characteristic (ROC). Relative to in the CNAG group, PG I and PGR levels in the other two groups exhibited depletion (P < 0.05); no statistical significance was observed in the PG II level among the three groups (P > 0.05); relative to the CNAG group, the G-17 level in the other two groups exhibited elevation (P < 0.05). Total Hp positive rate was 61.06 %, among which GC group exhibited the highest positive rate (72.00 %), and type I Hp positive rate also exhibited the highest in GC group (60.00 %). The type II Hp positive rate exhibited the highest in CNAG group (15.00 %). The PG I and PGR levels in type I Hp positive patients exhibited depletion relative to those in type II Hp positive patients, whereas PG II and G-17 levels exhibited elevation. When testing each indicator alone, the area under the curve (AUC) of PG I exhibited the highest in CNAG group, which was 0.874. When testing each indicator alone, AUC of Hp typing exhibited the highest in CAG group, which was 0.515. When testing each indicator alone, AUC of G-17 exhibited the highest in GC group, which was 0.787. The performance of combined detection was better than that of individual detection, with AUCs greater than 0.9 in three groups. In conclusion, changes in PG I, PG II, PGR and G-17 levels and Hp serotyping can receive application as screening indicators for chronic gastritis and GC, which can reflect relevant status of gastric mucosa to varying degrees. Combined detection of indicators has higher diagnostic performance and can receive application as an auxiliary diagnostic indicator in addition to gastroscopy biopsy, providing a reference basis for the formulation of clinical diagnosis and treatment plans.

Asunto(s)

Gastritis , Infecciones por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/microbiología , Gastritis/diagnóstico , Gastritis/microbiología , Masculino , Femenino , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/microbiología , Persona de Mediana Edad , Adulto , Enfermedad Crónica , Gastrinas/sangre , Anciano , Curva ROC , Serotipificación/métodos

RESUMEN

BACKGROUND: Chronic atrophic gastritis (CAG) is a chronic digestive disease. Modern research has revealed substantial evidence indicating that the progression of CAG is closely linked to the occurrence of oxidative stress-induced DNA damage and apoptosis in the gastric mucosa. Additionally, research has indicated that Costunolide (COS), the primary active compound found in Aucklandiae Radix, a traditional herb, exhibits antioxidant properties. Nevertheless, the therapeutic potential of COS in treating CAG and its molecular targets have not yet been determined. PURPOSE: The objective of this research was to explore the potential gastric mucosal protective effects and mechanisms of COS against N-Methyl-N´-nitro-N-nitrosoguanidine (MNNG)-induced CAG. METHODS: Firstly, the MNNG-induced rat CAG model was established in vivo. Occurrence of CAG was detected through macroscopic examination of the stomachs and H&E staining. Additionally, we assessed oxidative stress, DNA damage, and apoptosis using biochemical detection, Western blot, immunohistochemistry and immunofluorescence. Then, an in vitro model was developed to induce MNNG-induced damage in GES-1 cells, and the occurrence of cell damage was determined by Hoechst 33,342 staining and flow cytometry. Finally, the key targets of COS for the treatment of CAG were identified through molecular docking, cellular thermal shift assay (CETSA), and inhibitor ML385. RESULTS: In vivo studies demonstrated that COS promotes the expression of Nrf2 in gastric tissues. This led to an increased expression of SOD, GSH, HO-1, while reducing the production of MDA. Furthermore, COS inhibited DNA damage and apoptosis by suppressing the expression of γH2AX and PARP1 in gastric tissues. In vitro studies showed that COS effectively reversed apoptosis induced by MNNG in GES-1 cells. Additionally, COS interacted with Nrf2 to promote its expression. Furthermore, the expression levels of SOD, GSH, and HO-1 were augmented, while the generation of ROS and MDA was diminished. CONCLUSIONS: Our results indicate that COS exhibits therapeutic effects on CAG through the promotion of Nrf2 expression and inhibition of oxidative stress and DNA damage. Therefore, COS has the potential to provide new drugs for the treatment of CAG.

Asunto(s)

Apoptosis , Daño del ADN , Mucosa Gástrica , Gastritis Atrófica , Metilnitronitrosoguanidina , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Animales , Estrés Oxidativo/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Daño del ADN/efectos de los fármacos , Gastritis Atrófica/tratamiento farmacológico , Gastritis Atrófica/inducido químicamente , Masculino , Apoptosis/efectos de los fármacos , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Ratas , Humanos , Ratas Sprague-Dawley , Lactonas/farmacología , Línea Celular , Antioxidantes/farmacología , Modelos Animales de Enfermedad , Simulación del Acoplamiento Molecular , Sesquiterpenos

RESUMEN

BACKGROUND: The Correa sequence, initiated by Helicobacter pylori (H. pylori), commonly progresses to gastric cancer through the stage of chronic atrophic gastritis (CAG). Although eradication of H. pylori only reduces the risk of gastric cancer, it does not eliminate the risk for neoplastic progression. Yiwei Xiaoyu granules (YWXY) are a commonly used composite preparation in Chinese clinics. However, the pursuit of excellence in clinical trials and the establishment of standardized animal experiments are still needed to contribute to full understanding and application of traditional Chinese medicine in the treatment of CAG. AIM: To demonstrate the effectiveness of YWXY in patients with CAG and spleen-stomach deficiency syndrome (DSSS), by alleviating histological scores, improving response rates for pathological lesions, and achieving clinical efficacy in relieving DSSS symptoms. METHODS: We designed a double-blind, randomized, controlled trial. The study enrolled seventy-two H. pylori-negative patients (mean age, 52.3 years; 38 men) who were randomly allocated to either the treatment group or control group in a 1:1 ratio, and treated with 15 g YWXY or 0.36 g Weifuchun (WFC) tablet combined with the respective dummy for 24 wk. The pre-randomization phase resulted in the exclusion of 72 patients: 50 participants did not meet the inclusion criteria, 12 participants declined to participate, and 10 participants were excluded for various other reasons. Seven visits were conducted during the study, and histopathological examination with target endoscopic biopsy of narrow-band imaging was requested before the first and seventh visits. We also evaluated endoscopic performance scores, total symptom scores, serum pepsinogen and gastrin-17. RESULTS: Six patients did not complete the trial procedures. Treatment with YWXY improved the Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) stage, compared with WFC (P < 0.05). YWXY provided better relief from symptoms of DSSS and better improvement in serum gastric function, compared with WFC (P < 0.05). CONCLUSION: YWXY compared with WFC significantly reduced the risk of mild or moderate atrophic disease, according to OLGIM stage, significantly relieved symptoms of DSSS, and improved serum gastric function.