Chronic Atrophic Gastritis Rats Research Articles

Yangyin Huowei mixture alleviates chronic atrophic gastritis by inhibiting the IL-10/JAK1/STAT3 pathway.

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. To investigate the therapeutic effects of YYHWM and its underlying mechanisms in a CAG rat model. 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-1β, IL-6, and TNF-α. Western blot analysis was performed to evaluate protein expression of IL-10, JAK1, and STAT3. 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-1β, 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-1β, 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). 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.

Jianwei Xiaoyan granule ameliorates chronic atrophic gastritis by regulating HIF-1α-VEGF pathway

Ethnopharmacological relevanceJianwei 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. PurposeTo explore the material basis and potential mechanism of JWXYG in the treatment of CAG. MethodsIn 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. ResultsThirty-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. ConclusionJWXYG 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.

Yiqi Jiedu Huayu decoction inhibits precancerous lesions of chronic atrophic gastritis by inhibiting NLRP3 inflammasome-mediated pyroptosis.

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. To investigate the pharmacological effects of Yiqi Jiedu Huayu decoction (YJHD) on precancerous lesions of CAG. 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. 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. 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.

Luteolin targets the AGE-RAGE signaling to mitigate inflammation and ferroptosis in chronic atrophic gastritis.

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.

Integrated Approaches Revealed the Therapeutic Mechanisms of Zuojin Pill Against Gastric Mucosa Injury in a Rat Model with Chronic Atrophic Gastritis.

The Zuojin Pill (ZJP) is widely used for treating chronic atrophic gastritis (CAG) in clinical practice, effectively ameliorating symptoms such as vomiting, pain, and abdominal distension in patients. However, the underlying mechanisms of ZJP in treating CAG has not been fully elucidated. This study aimed to clarify the characteristic function of ZJP in the treatment of CAG and its potential mechanism. The CAG model was established by alternant administrations of ammonia solution and sodium deoxycholate, as well as an irregular diet. Therapeutic effects of ZJP on body weight, serum biochemical indexes and general condition were analyzed. HE staining and AB-PAS staining were analyzed to characterize the mucosal injury and the thickness of gastric mucosa. Furthermore, network pharmacology and molecular docking were used to predict the regulatory mechanism and main active components of ZJP in CAG treatment. RT-PCR, immunohistochemistry, immunofluorescence and Western blotting were used to measure the expression levels of apoptosis-related proteins, gastric mucosal barrier-associated proteins and PI3K/Akt signaling pathway proteins. The results demonstrated that ZJP significantly improved the general state of CAG rats, alleviated weight loss and gastric histological damage and reduced the serum biochemical indicators. Network pharmacology and molecular docking found that ZJP in treating CAG by inhibiting inflammation, suppressing apoptosis, and protecting the gastric mucosal barrier via the PI3K/Akt signaling pathway. Further experiments confirmed that ZJP obviously modulated the expression of key proteins involved in gastric mucosal cell apoptosis, such as Bax, Bad, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, Cytochrome C, Bcl-2, and Bcl-xl. Moreover, ZJP significantly reversed the protein expression of Occludin, ZO-1, Claudin-4 and E-cadherin. Our study revealed that ZJP treats CAG by inhibiting the PI3K/Akt signaling pathway. This research provided a scientific basis for the rational use of ZJP in clinical practice.

Effects of Rutaecarpine on Chronic Atrophic Gastritis Through Nucleotide-binding Oligomerization Domain-like Receptors and Inflammasomes

Abstract Objective: Chronic atrophic gastritis (CAG) is a complex and burdensome disease. However, side effects and compliance issues cannot be ignored due to the long treatment cycle. Numerous studies have confirmed the effectiveness of rutaecarpine (RUT) for treating digestive dysfunction. However, the potential mechanism of action of RUT in the context of CAG treatment remains unclear. This study aimed to explore the therapeutic effects and mechanisms of RUT in 1-methyl-3-nitro-1-nitrosoguanidine-induced CAG using network pharmacology, metabolomics, and traditional pharmacological approaches. Materials and Methods: Pathological tests and ELISA assays were used to observe the therapeutic effects of RUT treatment on CAG. Differential metabolites were identified using ultra-high-performance liquid chromatography-tandem mass spectrometry, and metabolism-related target genes were enriched. The same target genes were identified between RUT and CAG diseases. The intersectional target genes were uploaded to Cytoscape for enrichment, and the nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway was selected to validate the mechanisms of the study. Finally, cell pyroptosis status was evaluated using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, and the expressions of associated proteins of the NOD-like receptor signaling pathway were assessed by Western blotting and immunohistochemistry. Results: RUT alleviated gastric mucosal damage and significantly downregulated indicators associated with inflammation and gastric atrophy. A total of 29 intersection target genes were identified, and core pathways were obtained. The NOD-like receptor signaling pathway and pyroptosis status were selected to validate the mechanisms of RUT treatment in CAG rats. The expression of NOD-related proteins and downstream factors was downregulated in the RUT group. Conclusions: RUT exerts a pharmacological effect on relieving gastric damage in CAG rats by inhibiting NOD-like receptors and inflammasomes.

Exploration of the intestinal flora to reveal the important contribution of Radix Astragali to Huangqi Jianzhong Tang in treating chronic atrophic gastritis rats

Radix Astragali (Huangqi in Chinese, HQ) is a commonly used Chinese herbal medicine for thousands of years. In this study, A classic prescription Huangqi Jianzhong tang (HQJZ) was selected to evaluate the important effect of HQ on rats with chronic atrophic gastritis (CAG) from the perspective of intestinal flora in cecal contents samples. Traditional pharmacological indicators, including weight change, pathological examination and biochemical indicators showed that HQ exerted favorable contribution to HQJZ against CAG, where the efficiencies of HQ and HQJZ were better than HY (HQJZ prepared without HQ). An accurate strategy was adopted to screen out the differential metabolites in the metabolomis analysis of intestinal flora in cecal contents samples based on the optimal screening factors, including VIP (importance of variables in projection), FC (fold change), AUROC (area under the receiver operating characteristic curve) and -ln(p-value), which were evaluated based on their interpreting, grouping, and predicting abilities of the performed orthogonal partial least-squares-discriminate analysis (OPLS-DA) models. Ten altered differential metabolites were obtained and associated with the intestinal flora, which HQ exerted the important metabolic contributions to HQJZ. The efficacy on the diversity of intestinal flora and their correlations with the altered metabolites further showed the important role of HQ in HQJZ composition. This work provided valuable approach for looking for potential biomarkers associated with metabolomics research with more accuracy, and provided new insights into the mechanisms to explain the efficacy of HQ contributing to HQJZ formula.

Integrating metabolomics, 16S rRNA sequencing, network pharmacology, and metorigin to explore the mechanism of Cinnamomi Cortex in treating chronic atrophic gastritis rats

BackgroundCinnamomi cortex called as Rougui (RG) in Chinese was a widely used food-medicine homology. RG has the potential to treat chronic atrophic gastritis (CAG), a disease with widespread impact in the Chinese population. PurposeThis study aimed to explore its mechanism against CAG based on amalgamated strategies. MethodsNetwork pharmacology was used to predict the potential effective components and the core targets of RG against CAG based on the comprehensive chemical characterization using UHPLC-Q/TOF MS (ultra high performance liquid chromatogramphy-quadrupole/time-of-flight mass spectrometry). The CAG animals model were further used to validate its pharmacodynamics, of which gut microbiota of caecal contents were analyzed by integrating metabolomics, 16S rRNA sequencing, Metorigin metabolite traceability analysis and molecular docking to explore its action mechanism. ResultsNetwork pharmacology firstly predicted the efficacy of RG was attributed to four effective components and seven targets. Metabolomics of caecal contents in CAG rats revealed primary bile acid biosynthesis was its targeted metabolic pathway associated with the metabolism of gut microbiota coupled with Metorigin traceability analysis. 16S rRNA sequencing showed that RG treated CAG by regulating the imbalance of gut microbiota. Molecular docking further confirmed that the effective components of RG could intervene with potential targets, metorigin analysis pathway, and key enzymes of gut microbiota metabolic pathways. ConclusionOur results proved that RG exerted favorable effect on CAG. The four active ingredients (quercetin, kaempferol, oleic acid, and (-)-epicatechin) of RG were the key to exert drug effect, which could targeted the core target of CAG, primary bile acid biosynthesis and intestinal flora metabolic pathways.

High Hepcidin Levels Promote Abnormal Iron Metabolism and Ferroptosis in Chronic Atrophic Gastritis.

Chronic atrophic gastritis (CAG) is a chronic inflammatory disease and premalignant lesion of gastric cancer. As an antimicrobial peptide, hepcidin can maintain iron metabolic balance and is susceptible to inflammation. The objective of this study was to clarify whether hepcidin is involved in abnormal iron metabolism and ferroptosis during CAG pathogenesis. Non-atrophic gastritis (NAG) and chronic atrophic gastritis (CAG) patient pathology slides were collected, and related protein expression was detected by immunohistochemical staining. The CAG rat model was established using MNNG combined with an irregular diet. CAG patients and rats exhibited iron deposition in gastric tissue. CAG-induced ferroptosis in the stomach was characterized by decreased GPX4 and FTH levels and increased 4-HNE levels. Hepcidin, which is mainly located in parietal cells, was elevated in CAG gastric tissue. The high gastric level of hepcidin inhibited iron absorption in the duodenum by decreasing the protein expression of DMT1 and FPN1. In addition, the IL-6/STAT3 signaling pathway induced hepcidin production in gastric tissue. Our results showed that the high level of gastric hepcidin induced ferroptosis in the stomach but also inhibited iron absorption in the intestines. Inhibiting hepcidin might be a new strategy for the prevention of CAG in the future.

Huangqi Jianzhong Tang treats chronic atrophic gastritis rats by regulating intestinal flora and conjugated bile acid metabolism.

Huangqi Jianzhong Tang (HQJZ) is effective for treating chronic atrophic gastritis (CAG). The present study was carried out to reveal the mechanism of HQJZ in CAG rats. The metabolism and microbial composition of the cecal contents in CAG rats were analyzed through the integration of an untargeted metabolomic approach using ultra-high-performance liquid chromatography coupled with the quadrupole-time of flight mass spectrometry (UHPLC-QTOF-MS) and 16S rRNA gene sequencing, respectively. Finally, MetOrigin analyses were performed to explore the relationship between differential metabolites and intestinal flora. The results showed that HQJZ could significantly regulate metabolic disorders, especially conjugated acid metabolites. 16S rRNA gene sequencing analysis illustrated that HQJZ decreased the abundance of Acetobacter, Desulfovibrio, Escherichia, and Shigella. MetOrigin metabolite traceability analysis showed that the six bile acids associated with HQJZ efficacy included three bacteria-host cometabolites, which were involved in the primary bile acid biosynthesis pathway. Research presented here confirmed that conjugated bile acid metabolism was key to the treatment of CAG by HQJZ and correlates strongly with Bacteroides acidifaciens and Prevotella copri. These findings provide new insights into the mechanisms to explain the efficacy of HQJZ.

Granule Dendrobii suppresses chronic atrophic gastritis induced by N-methyl-N'-nitro-N-nitrosoguanidine by modulating the gastrointestinal bacteria in rats.

Chronic atrophic gastritis (CAG) is an important stage in the transformation of the normal gastric mucosa into gastric cancer. Granule Dendrobii (GD), a proprietary Chinese medicine, has proven clinical efficacy in treating CAG. GD might promote the reversal of precancerous lesions by improving them in CAG patients. However, the mechanism of GD in CAG treatment is relatively less understood. Here, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced CAG rats were treated with GD and its efficacy was evaluated by observing the changes in the rats' weight and the pathology of gastric tissues. The potential effect of GD on the bacteria was predicted and verified in the large and small intestines and stomachs of CAG rats using amplicon sequencing and RT-qPCR. The results showed that GD could ameliorate the symptoms of body weight loss in CAG rats. Hematoxylin-Eosin (HE) and Alcian Blue (AB) staining showed that GD significantly improved the pathological state of the gastric mucosa in CAG rats. The relative abundance (RA) of Lactobacillus and Turicibacter significantly decreased after GD intervention compared with that of the model group (P < 0.05), indicating that GD might improve CAG by regulating the RA of Lactobacillus and Turicibacter. These findings revealed that Lactobacillus and Turicibacter as bacteria agents associated with gastritis, have the potential to inhibit gastric cancer, especially Turicibacter maybe another pathogen of CAG besides Helicobacter pylori (HP), which is worthy of further study. Meanwhile, the findings provided new ideas and materials for the research and development of new CAG drugs.

Bile acid metabolism involved into the therapeutic action of Xiaojianzhong Tang via gut microbiota to treat chronic atrophic gastritis in rats

BackgroundAs a classical traditional Chinese medicine (TCM), Xiaojianzhong Tang (XJZ) is effective in treating chronic atrophic gastritis (CAG). However, the pharmacological mechanism of XJZ has not been fully explained. PurposeThe purpose of this study was to investigate the mechanism of XJZ against CAG rats via gut microbiome using a multi-omics approach. MethodsThe rat cecal contents were analyzed through the integration of an untargeted metabolomic approach based on ultra-high performance liquid chromatography coupled with the quadrupole-time of flight mass spectrometry (UHPLC-QTOF-MS) and 16S rRNA gene sequencing. Finally, the interaction of differential metabolites with bile acid (BA)-related targets was verified by molecular docking. ResultsA new strategy was adopted to screen out the differential metabolites based on the comprehensive evaluation of VIP, |log2(FC)|, -ln(p-value) and ǀp(corr)ǀ. As results, XJZ showed favor regulations on the screened metabolites, cholic acid, deoxycholic acid, glycoursodeoxycholic acid, taurochenodesoxycholic acid, docosahexaenoic acid and L-isoleucine. The 16S rRNA gene sequencing analysis showed that XJZ could regulate gut microbiota disturbances in CAG rats, especially bile acid (BA) metabolism-related bacteria (Butyricimonas, Desulfovibrio, Bacteroides, Parabacteroides, Acetobacter and Alistipes). Molecular docking further showed that the differential metabolites regulated by XJZ had a good docking effect on BA-related targets. ConclusionThe current work indicated that XJZ's therapeutic action was strongly linked to BA-related microorganisms and metabolic processes. These findings provided new insights into the effects of XJZ for the treatment of CAG.

Integrated pharmacokinetics of Huangqi Jianzhong Tang in normal and chronic atrophic gastritis rats

Huangqi Jianzhong Tang (HQJZ) is a famous traditional Chinese medicine formula widely used in the treatment of gastrointestinal diseases in China. In this study, an ultra-performance liquid chromatography-mass spectrometry (UHPLC-MS/MS) was used to study the pharmacokinetics of 12 prototypical components and one metabolite in HQJZ in normal and chronic atrophic gastritis rats. The results showed that the area under the concentration-time curve and peak concentration of most flavonoids and flavonoid glycosides were decreased, and the half-life and mean residence time were significantly increased, which indicated that the absorption of drugs in disease was decreased less and for longer in vivo. Then, an integrated pharmacokinetic study was carried out using the pharmacokinetic parameter model integration of each component. The results showed that the absorption of drugs in vivo with disease was reduced, and the absorption speed of flavonoids and flavonoid glycosides was accelerated. This study will provide the basis for the clinical medication safety of HQJZ.

Jian-Pi-Yi-Qi-Fang ameliorates chronic atrophic gastritis in rats through promoting the proliferation and differentiation of gastric stem cells.

BackgroundJian-Pi-Yi-Qi-Fang (JPYQF) is a traditional Chinese medicine (TCM) herbal formula for treating chronic atrophic gastritis (CAG) in the clinic; however, its related mechanism remains unclear. The purpose of this study was to explore the potential mechanisms of JPYQF in treating CAG by examining proteins and genes related to the proliferation and differentiation of gastric stem cells and Wnt signaling.MethodsA CAG model was established in Sprague-Dawley (SD) rats which were induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and ranitidine. We randomly divided 25 CAG rats into 5 groups: the model group, positive drug group, low-dose group of JPYQF (JPYQF-L), middle-dose group of JPYQF (JPYQF-M), and high-dose group of JPYQF (JPYQF-H), with 5 rats of the same age classified into the control group. The body weight of rats was measured and their gastric morphology was visually assessed. Furthermore, pathological analysis of rat gastric tissue was performed. The expression levels of proteins and genes associated with the proliferation and differentiation of gastric stem cells and Wnt signaling were measured via immunohistochemistry and reverse transcription quantitative polymerase chain reaction (RT-qPCR).ResultsCompared with the model group, treatment with JPYQF increased the body weight of the rats, and relieved the gastric atrophy and inflammation. Compared with the control group, the protein and messenger RNA (mRNA) expression levels of gastric stem cell proliferation and differentiation markers Lgr5, Sox2, Ki67, PCNA, Muc5AC, and Wnt signaling initiator Wnt3A and enhancer R-spondin-1 (Rspo1) were decreased in the model group. Treatment with JPYQF increased the protein and mRNA expression levels of these markers.ConclusionsThe Wnt signaling of CAG rats may be in a low activation state, which inhibits the proliferation and differentiation of gastric stem cells, so that gland cells cannot be replenished in time to repair the damaged gastric mucosa. The TCM formula JPYQF could enhance Wnt signaling to promote the restricted proliferation and normal differentiation of gastric stem cells, thereby improving gastric mucosal atrophy in CAG rats, which provides a novel and robust theoretical basis for CAG treatment.

Effects of Granule Dendrobii on chronic atrophic gastritis induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats.

BACKGROUND Dendrobium officinale is an herb of Traditional Chinese Medicine (TCM) commonly used for treating stomach diseases. One formula of Granule Dendrobii (GD) consists of Dendrobium officinale and American Ginseng (Radix Panacis quinquefolii), and is a potent TCM product in China. Whether treatment with GD can promote gastric acid secretion and alleviate gastric gland atrophy in chronic atrophic gastritis (CAG) requires verification.AIMTo determine the effect of GD treatment on CAG and its potential cellular mechanism.METHODSA CAG model was induced by feeding rats N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for 12 wk. After oral administration of low, moderate, and high doses of GD in CAG rats for 8 wk, its effects on body weight, gastric mucosa histology, mucosal atrophy, intestinal metaplasia, immunohistochemical staining of proliferating cell nuclear antigen (PCNA) and B-cell lymphoma-2, and hemoglobin and red blood cells were examined.RESULTSThe body weights of MNNG-induced CAG model rats before treatment (143.5 ± 14.26 g) were significantly lower than that of healthy rats (220.2 ± 31.20 g, P < 0.01). At the 8th week of treatment, the body weights of rats in the low-, moderate-, and high-dose groups of GD (220.1 ± 36.62 g) were significantly higher than those in the untreated group (173.3 ± 28.09 g, all P < 0.01). The level of inflammation in gastric tissue of the high-dose group (1.68 ± 0.54) was significantly reduced (P < 0.01) compared with that of the untreated group (3.00 ± 0.00, P < 0.05). The number and thickness of gastric glands in the high-dose group (31.50 ± 6.07/mm, 306.4 ± 49.32 µm) were significantly higher than those in the untreated group (26.86 ± 6.41/mm, 244.3 ± 51.82 µm, respectively, P < 0.01 and P < 0.05), indicating improved atrophy of gastric mucosa. The areas of intestinal metaplasia were significantly lower in the high-dose group (1.74% ± 1.13%), medium-dose group (1.81% ± 0.66%) and low-dose group (2.36% ± 1.08%) than in the untreated group (3.91% ± 0.96%, all P < 0.01). The expression of PCNA in high-dose group was significantly reduced compared with that in untreated group (P < 0.01). Hemoglobin level in the high-dose group (145.3 ± 5.90 g/L), medium-dose group (139.3 ± 5.71 g/L) and low-dose group (137.5 ± 7.56 g/L) was markedly increased compared with the untreated group (132.1 ± 7.76 g/L; P < 0.01 or P < 0.05).CONCLUSIONTreatment with GD for 8 wk demonstrate that GD is effective in the treatment of CAG in the MNNG model by improving the histopathology of gastric mucosa, reversing gastric atrophy and intestinal metaplasia, and alleviating gastric inflammation.

Regulation of gut microbiota of Astragali Radix in treating for chronic atrophic gastritis rats based on metabolomics coupled with 16S rRNA gene sequencing

Astragali Radix (HQ), a common traditional Chinese medicine (TCM), is widely used to treat chronic atrophic gastritis (CAG). However, its mechanism in treating CAG is still not clear. Accumulating evidence highlights the link between gut microbiota and CAG. We hypothesized that the gut microbiota might be involved in the effect of HQ. Ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC-Q-TOF/MS) based metabolomics and 16S rRNA gene sequencing techniques of the cecal contents were applied to study its mechanisms. As a result, nine metabolites and fifteen gut microbiotas changed significantly in cecal contents samples between control group and model group. Among them, two metabolites (7-keto-3A ·12-α-hydroxyalkanoic acid and deoxycholic acid) and two gut microbiota genera (Acetobacter and Escherichia), had the most obvious callback effect after the administration of HQ. Sixty-seven correlated pairs exhibited the significant link between the involved metabolites and gut microbiotas through the correlation analysis, where two strong correlation pairs: Tetrahydrohydroxone ∼ Bacteroides (r = 0.895) and Deoxycholic acid ∼ Acetobacter (r = −0.843) were regulated by HQ. The results showed that HQ had the potential protection from metabolic perturbation involved into gut microbiotas induced by CAG. Two gut microbiotas, Acetobacter and Escherichia, and two metabolites, 7-keto-3A ·12-α-hydroxyalkanoic acid and deoxycholic acid were the potential targets of HQ.

Exploration of Tuina Effect and Mechanism in Chronic Atrophic Gastritis Rats.

Chronic atrophic gastritis is a very common condition in the general clinical practice of gastroenterology. Tuina treatment is widely used clinically. The aim of our study was to investigate the mechanisms of tuina in rats with chronic atrophic gastritis. Fifty-six specific pathogen-free grade rats were employed for our study. They were divided into 5 groups and treated differ- ently. Body weight was recorded every week, and their small intestine propulsive ratio was measured after intragastric administration of carbon powder. Histopathological observation of gastric tissues was performed using hematoxylin and eosin staining. The levels of motilin and gastrin in serum were detected by enzyme-linked immunosorbent assay, and the expression levels of Bcl-2 and cytochrome C were measured by the western blot assay. There was no significant difference in body weight and small intestine propulsive ratio between the chronic atrophic gastritis model group and the tuina group (P > .05). However, we can see some significant changes in histomorphology after treatment with tuina. For example, the atrophy of gastric mucosal epithelium and glands had improved, and the inflammatory cells infiltrating the lamina propria were decreased significantly. Moreover, the level of gastrointestinal hormone GAS was increased (P < .001), and there was no statistically significant difference in motilin, Bcl-2, and cytochrome-c after treatment with tuina (P > .05). Our research demonstrated the effectiveness of tuina treatment on chronic atrophic gastritis with a possible underlying mechanism that affected the secretion of gastric acid, which could provide some useful information for clinical application.

Therapeutic effect of Qinghuayin against chronic atrophic gastritis through the inhibition of toll or interleukin-1 receptor domain-containing adaptor inducing interferon-β signaling pathway.

To examine the efficacy of Qinghuayin (, QHY) in rat chronic atrophic gastritis (CAG) models and explored the molecular mechanism of QHY in treating CAG. In total, 65 Wistar rats were randomly divided into the control (= 10) and CAG groups ( = 55). CAG model rats were further divided into five groups: model ( = 10), vitacoenzyme ( = 10), low-dose QHY ( = 10), medium-dose QHY ( = 10), and high-dose QHY groups ( = 10). We analyzed histopathological changes using hematoxylin and eosin staining and measured interleukin (IL)-6 and IL-8 levels in serum using enzyme-linked immunosorbent assay (ELISA) (Boster Bio, Pleasanton, USA). In addition, gastrin (GAS), pepsinogen I (PGI), and PGII expressions were evaluated using ELISA. The protein and mRNA expression of toll-like receptor 4 (TLR4) and toll or interleukin-1 receptor domain-containing adaptor inducing interferon-β (TRIF) was detected by Western blotting and quantitative reverse transcription-polymerase chain reaction, respectively. Our results revealed that histopathological changes in CAG model rates could be restored by low-, medium-, and high-dose QHY. The changes in GAS and PGI/II expression demonstrated that QHY improved CAG. Serum IL-6 and IL-levels were decreased by QHY administration. TLR4 and TRIF were upregulated at the mRNA and protein levels in the model group but downregulated by QHY administration. We concluded that QHY could effectively improve the histopathological changes of the gastric mucosa induced by CAG in rats. The therapeutic mechanism of QHY may be related to inhibition of the inflammatory factors IL-6 and IL-8 and suppression of TLR4/TRIF mRNA and protein expression.

Comparison of stimulation-induced local changes of expression of local Meckel cell-related proteins and neuropeptides and number of mast cells among acupuncture and moxibustion alone or in combination in chronic atrophic gastritis rats

To compare the effects of acupuncture and moxibustion alone or in combination on the number of mast cells and expression levels of cytoketatin 18 (CK18) and CK19 (marker of Meckel cells), and calcitonin gene-related peptide (CGRP), neuropeptide-Y (NPY) and bradykinin (BK) in the local acupoint area of rats with chronic atrophic gastritis (CAG). Fifty male SD rats were randomly divided into normal, CAG model, moxibustion, acupuncture and acupuncture+moxi-bustion groups (10 rats in each group). The CAG model was established by gavage of 1-methyl-3-nitro-1-nitrosoguanidine (170 μg/mL,1 mL/100 g, once a week) and 40% ethanol solution (twice a week) for 12 consecutive weeks. After successful establishment of CAG model, moxibustion, manual acupuncture or acupuncture+moxibustion was applied to bilateral "Zusanli" (ST36) and "Zhongwan"(CV12) for 15 min, once daily for 14 consecutive days. At the end of the experiment, the gastric mucosal tissues were collected for observing histopathological changes of gastric mucosa after H.E. staining, and the tissues of the stimulated ST36 region collected for detecting the expression levels of CK18, CK19, CGRP, NPY and BK and the number of mast cells in the local ST36 region by immunohistochemistry. Compared with the normal group, the number of mast cells, the expression levels of CK19, NPY and BK in the ST36 area were significantly increased (P<0.05), and the expression level of CGRP was apparently decreased (P<0.05) in the model group. In comparison with the model group, the number of mast cells and the expression levels of CGRP and NPY in the moxibustion group, the expression of CGRP in the acupuncture group, and the number of mast cells, as well as the expression levels of CK18, CK19 and CGRP in the acupuncture+moxibustion group were significantly up-re-gulated (P<0.05). The effect of acupuncture combined with moxibustion was obviously superior to that of moxibustion or acupuncture in up-regulating the expression of CK18 and CK19 (P<0.05) and superior to that of moxibustion in down-regulating BK expressio level (P<0.05). No significant changes were found in the expression of CK18 after modeling (vs the normal group), in the expression levels of CK18, CK19 and BK after moxibustion and acupuncture (vs the model group), in the number of mast cells and expression of NPY after acupuncture (vs the model group), and in the expression levels of NPY and BK after acupuncture+moxibustion (vs the model group) (P>0.05). H.E. staining showed infiltration of many lymphocytes in the gastric mucosa and submucosal layers, atrophy and necrosis of lots of main cells with vacuole-like changes, and disordered arrangement of the atrophic glands in the model group, which was milder particularly in the acupuncture + moxibustion group. Acupuncture combined with moxibustion of ST36 can up-regulate the levels of local CK18, CK19 and CGRP proteins and number of mast cells, moxibustion may up-regulate the levels of CGRP and NPY and number of mast cells, while acupuncture may up-regulate the expression of CGRP in the local stimulated area in CAG rats.

16S rRNA sequencing-based evaluation of the protective effects of Hua-Zhuo-Jie-Du on rats with chronic atrophic gastritis

BackgroundDisturbance of the intestinal flora is a pathogenic factor for chronic atrophic gastritis (CAG). Hua-Zhuo-Jie-Du (HZJD) has been shown to be an effective Chinese herbal preparation for treating CAG. However, the effects of HZJD on the intestinal flora of CAG is unclear. In this study, we probed the regulating effects of HZJD on intestinal microbes in CAG rats using 16S rRNA gene sequencing.MethodsHigh-performance liquid chromatography (HPLC) analysis was used to perform quality control of HZJD preparations. We then administered 1-methyl-3-nitro-1-nitrosoguanidine (200 μg/ml) to Sprague–Dawley rats to establish a CAG model. HZJD and vitacoenzyme were administered orally to these rats over a 10 week period. Hematoxylin and eosin (H&E) staining was performed to observe the histopathology of CAG rats. A rarefaction curve, species accumulation curve, Chao1 index, and ACE index were calculated to assess the alpha diversity. Principal component analysis (PCA), non-metric multi-dimensional scaling (NMDS), and unweighted pair group method with arithmetic mean (UPGMA) were conducted to examine the beta diversity. The LEfSe method was used to identify differential bacteria. Differential function analysis used PCA based on KEGG function prediction.ResultsHPLC showed that our HZJD preparation method was feasible. H&E staining showed that HZJD significantly improved the pathological state of the gastric mucosa in CAG rats. The rarefaction curve and species accumulation curve showed that the sequencing data were reasonable. The Chao1 and ACE indices were significantly increased in CAG rats compared to the N group. Following HZJD and vitacoenzyme treatment, the Chao1 and ACE indices were decreased. PCA, NMDS, and UPGMA results showed that the M group was separated from the N, HZJD, and V groups, and LEfSe results showed that the relative abundance of Akkermansia, Oscillospira, Prevotella, and CF231 were significantly higher in the N group. Proteobacteria and Escherichia were significantly enriched in the M group, Allobaculum, Bacteroides, Jeotgalicoccus, Corynebacterium, and Sporosarcina were significantly enriched in the V group, and Firmicutes, Lactobacillus, and Turicibacter were significantly enriched in the HZJD group.ConclusionHZJD exhibited a therapeutic effect on the intestinal flora of CAG rats.