Chronic Atrophic Gastritis Rats Research Articles

A Web-Based Pharmacological Approach to the Mechanism of Action of Rhizoma Phragmitis and Rhizoma Curcumae in the Treatment of Chronic Atrophic Gastritis.

Objective To analyze and test the effect of Rhizoma phragmitis and Rhizoma curcumae on the network pharmacology of MAPK (mitogen-activated protein kinase) and TNF (tumor necrosis factor) signaling channels and inflammatory factor target gene regulation in successful modeling of chronic atrophic gastritis rats. Methods Rats with chronic atrophic gastritis that were modeled successfully were randomly divided into control and study groups and were treated with conventional western medicine or Rhizoma phragmitis and Rhizoma curcumae, respectively. The pharmacological mechanism of action and efficacy were evaluated. Results The treatment efficiency was 76.32% and 97.37% in the control and study group, respectively. After treatment, the serum tumor necrosis factor-α (TNF-α) and serum malondialdehyde (MDA) levels in the study group were lower than those in the control group and the serum epidermal growth factor (EGF) and superoxide dismutase (SOD) levels in the study group were higher than those in the control group (P < 0.05); the pain behavioral scores in the study group were lower than those in the control group, and the free acid quantity and total acid quantity in the study group were higher than those in the control group (P < 0.05); the serum MTL index in the study group was higher than that in the control group, and the serum gastrin (GAS) and pepsinogen I (PG I) indices in the study group were lower than those in the control group (P < 0.05); the number of 24-hour reflux in the study group was less than that in the control group (P < 0.05), and the longest reflux time in the study group was lower than that in the control group (P < 0.05). Conclusion Based on the network pharmacological results, Rhizoma phragmitis and Rhizoma curcumae will modulate MAPK, TNF signaling circuits, and inflammatory factor target genes in the chronic atrophic gastritis rat model. This treatment protocol is efficient and beneficial to enhance the gastric function of the chronic atrophic gastritis rat model, while it can alleviate the inflammatory response and significantly reduce the number and duration of reflux, which is a safe and reliable treatment modality.

Astragalus polysaccharide inhibits apoptosis and inflammation to alleviate chronic atrophic gastritis through NF-κB signaling pathway in rats

Chronic atrophic gastritis (CAG) is a process of inflammation characterized by injured gastric mucosal epithelium leading to reduction of mucosal glands, often accompanied by intestinal or pseudopyloric metaplasia. Astragalus polysaccharide (APS) is reported to improve gastric mucosal damage and inflammation, but its role in CAG remains elusive. Therefore, we intended to analyze the impact of APS on CAG and its potential mechanism to provide novel insight into the treatment for the disorder. After establishment of CAG model using MNNG method, the rats were administered Vitazyme (200 mg/kg), or low, moderate and high concentration of APS (20, 40, 60 mg/kg), respectively, with healthy rats as controls and some CAG rats untreated. After that, the rat gastric tissues were pathologically examined and ELISA, Western blot analysis and staining were carried out to assess the impact of treatment on inflammation and apoptosis Pathologically, APS treatment alleviated the pathological changes of CAG rats, reducing inflammatory cell infiltration and inflammation. Besides, APS significantly diminished the content of pro-inflammatory factors and decreased the level of gastrointestinal hormones. In the presence of APS, the apoptosis of gastric mucosal cells was inhibited and the p-NF-κB p65 and p-IKKα/β expression was decreased. Collectively, APS could mitigate inflammation and gastric mucosal damage in CAG, as it also suppresses the process of apoptosis and inactivates the NF-κB signaling pathway. In a word, APS treatment improves CAG via NF-κB pathway.

Zuojin Pill attenuates Helicobacter pylori-induced chronic atrophic gastritis in rats and improves gastric epithelial cells function in GES-1 cells

Ethnopharmacological relevanceZuojin pill (ZJP), a classical Chinese medicine formula, has been widely applied in Chinese clinical practice for the treatment of gastric injury such as acute gastric lesion, acute gastric mucosal injury, chronic unpredictable mild stress, gastroesophageal reflux disease, etc, thereby exerting anti-chronic atrophic gastritis (CAG) effects in traditional Chinese herbal medicine. Aim of the studyThis study was aimed to explore the therapeutic effects and molecular mechanisms of ZJP on Helicobacter pylori (H. pylori)-induced CAG based on the comprehensive approaches. Materials and methodsSprague-Dawley rats were infected with H. pylori for 8 weeks to establish CAG model. Then, rats in the ZJP groups received doses of 0.63, 1.26, and 2.52 g/kg ZJP for 4 weeks. Therapeutic effects of ZJP on serum indices and the histopathology of the gastric were analyzed in vivo. Moreover, GES-1 cells were infected with H. pylori to establish gastric epithelial cell injury model in vitro. Cell viability and gastric epithelial cell morphology were detected by a high-content screening (HCS) assay. Furthermore, the relative mRNA and protein expression of JMJD2B/COX-2/VEGF axis and HMGB1/NF-κB signaling pathway in vivo and in vitro were determined by RT-PCR and Western Blotting, respectively. ResultsThe results showed that the therapeutic effects of ZJP on CAG rats were presented in down-regulation serum biochemical indices and alleviating histological damage of gastric tissue. ZJP could dose-dependently decrease the serum IL-6, MCP-1, PGE2, TNF-α, and VEGF level and significantly improved gastric tissue inflammatory lesions. Besides, ZJP has an effect on increasing cell proliferation of GES-1 cells, ameliorating H. pylori-induced gastric epithelial cell damage. It was found that ZJP has a down-regulating effect on inflammatory reaction and could inhibit the relative mRNA and protein expression of JMJD2B/COX-2/VEGF axis and HMGB1/NF-κB signaling pathway in vivo and in vitro, including JMJD2B, COX-2, VEGF, VEGFR1, and VEGFR2, which in turn reduced the damage of gastric mucosal cells. ConclusionsThe results suggested that ZJP exerts therapeutic effects on H. pylori-induced CAG by inhibiting the JMJD2B/COX-2/VEGF axis and HMGB1/NF-κB signaling pathway. These findings deeply explained why ZJP could be used to treat CAG clinically and clarified its pharmacological effect and potential mechanism in the treatment of CAG.

Therapeutic effect of berberine on chronic atrophic gastritis based on plasma and urine metabolisms

The purpose of this study was to investigate the therapeutic effect of berberine (BBR) on chronic atrophic gastritis (CAG) and its potential mechanism. The effects of BBR on gastric histopathology, serum biochemical indexes and inflammatory factors in CAG rats were assessed. Moreover, plasma and urine metabolomics based on ultra high performance liquid chromatography-quadrupole-time-of-flight mass spectrometer (UHPLC-Q-TOF/MS) were used to identify potential metabolic markers and possible pathways of BBR in the treatment of CAG. The results showed that BBR could significantly improve the pathological characteristics of gastric tissue, alleviate the serum biochemical indexes and reduce the mRNA expression of nuclear factor-κB, tumor necrosis factor-α, Cyclooxygenase-2, monocyte chemoattractant protein-1, Interleukin-17A and I interferon-γ. The results of metabolomic analysis show that the therapeutic effect of BBR on CAG may be related to the regulation of 15 metabolic markers and 12 metabolic pathways, which may be the potential mechanism for the treatment of CAG. This study provides new insights for elucidating the mechanism of BBR improving CAG.

Jianpiyiqi formula ameliorates chronic atrophic gastritis in rats by modulating the Wnt/β-catenin signaling pathway.

Jianpiyiqi formula is a Traditional Chinese Medicine (TCM) prescription and is used for the clinical treatment of patients with chronic atrophic gastritis (CAG). The aim of the present study was to examine the underlying mechanisms of Jianpiyiqi formula treatment for CAG via the Wnt/β-catenin signaling pathway. The high-performance liquid chromatography (HPLC) chromatogram of Jianpiyiqi formula was constructed. A CAG rat model induced by N-methyl-N'-nitro-N-nitrosoguanidine and ranitidine was established. The body weight and food intake of the rats was recorded and rat gastric morphology was visually examined. Pathological analysis of rat gastric tissue was also performed. The levels of gastrin (GAS), pepsin (PP), somatostatin (SS) and prostaglandin E2 (PGE2) in rat serum were detected using ELISAs. The expression levels of proteins and genes associated with the Wnt/β-catenin signaling pathway were measured via immunohistochemistry and reverse transcription-quantitative PCR. The HPLC chromatogram of Jianpiyiqi formula was determined and as active components, liquiritin and hesperidin were identified from the chromatogram. Compared with the blank group, the body weight and feed intake of the rats were decreased, and gastric mucosal atrophy and inflammation appeared in the model group. Treatment with Jianpiyiqi formula increased the body weight and feed intake of the rats, as well as relieved the gastric atrophy and inflammation. The contents of GAS, PP, SS and PGE2 were significantly reduced in the model group compared with the blank group. Jianpiyiqi formula significantly increased GAS, PP, SS and PGE2 levels in serum of rats with CAG. In the model group, Wnt1, β-catenin and cyclin D1 protein expression levels were increased, and glycogen synthase kinase-3β (GSK-3β) protein expression levels were decreased. Jianpiyiqi formula decreased the protein expression levels of Wnt1, β-catenin and cyclin D1 and increased the protein expression levels of GSK-3β. Compared with the blank group, the mRNA expression levels of Wnt1, Wnt5a, β-catenin, cyclin D1 and MMP7 were upregulated, and the mRNA expression levels of GSK-3β were downregulated in the model group. Treatment with Jianpiyiqi formula downregulated the mRNA expression levels of Wnt1, Wnt5a, β-catenin, cyclin D1 and MMP7 and upregulated the mRNA expression levels of GSK-3β. All of the experimental results indicated that Jianpiyiqi formula exerted a therapeutic effect on rats with CAG and inhibited the activation of the Wnt/β-catenin signaling pathway. Thus, Jianpiyiqi formula, as an effective TCM prescription for treating patients with CAG, may be more widely used in the clinic.

Therapeutic effects and potential mechanism of dehydroevodiamine on N-methyl-N′-nitro-N-nitrosoguanidine-induced chronic atrophic gastritis

BackgroundsDehydroevodiamine (DHE) is a quinazoline alkaloid isolated from a Chinese herbal medicine, named Euodiae Fructus (Wu-Zhu-Yu in Chinese). This study aimed to investigate the therapeutic effects and potential mechanism of DHE on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced chronic atrophic gastritis (CAG) based on integrated approaches. MethodsTherapeutic effects of DHE on serum biochemical indices and histopathology of gastric tissue in MNNG-induced CAG rats were analyzed. MNNG-induced GES-1 human gastric epithelial cell injury model was established. Cell viability and proliferation was quantified by a cell counting kit-8 assay. Cell morphology and mitochondrial membrane potential (MMP) were detected by a high content screening (HCS) assay. Cell migration and invasion were detected by a Transwell chamber. Moreover, UHPLC-Q-TOF/MS was performed to investigate the potential metabolites and signaling pathway affecting the protective effects of DHE on MNNG-induced cell migration and invasion of GES-1. Furthermore, in view of the key role of angiogenesis in the transformation of inflammation and cancer, this study explored relative mRNA and protein expression levels of HIF-1α-mediated VEGF pathway in vivo and in vitro by RT-PCR and Western Blotting, respectively. ResultsThe results showed that the therapeutic effects of DHE on CAG rats were presented in down-regulation serum biochemical indices and alleviating histological damage of gastric tissue. Besides, DHE has an effect on increasing cell proliferation of GES-1 cells, ameliorating MNNG-induced gastric epithelial cell damage and mitochondrial dysfunction. In addition, DHE could inhibit MNNG induced migration and invasion of GES-1 cells. Cell metabolomics analyses showed that the protective effect of DHE on GES-1 cells is mainly associated with the regulation of inflammation metabolites and energy metabolism related pathways. It was found that DHE has a regulating effect on tumor angiogenesis and can inhibit the relative gene and protein expression of HIF-1α-mediated VEGF signaling pathway. ConclusionsThe present work highlighted the role of DHE ameliorated gastric injury in MNNG-induced CAG rats in vivo and GES-1 cell migration in vitro by inhibiting HIF-1α/VEGF angiogenesis pathway. These results suggest that DHE may be the effective components of Euodiae Fructus, which provides a new agent for the treatment of CAG.

Explore the effects of Shidan granules on chronic atrophic gastritis using LC-MS based plasma metabolomics study.

Shidan granule (SDG), a traditional Chinese medicine in-hospital preparation, has been demonstrated to exert good effects on chronic atrophic gastritis (CAG) in clinics. However, the underlying mechanism of SDG against CAG is still unclear. This study utilized an untargeted plasma metabolomics approach to explore the potential mechanism of SDG in CAG rats using LC-MS and pattern recognition analysis. The results indicated that SDG could effectively improve the biochemical indexes and pathology features of CAG rats. Nineteen potential biomarkers (variable importance in projection>1 and P<0.05) contributing to CAG progress were identified. After SDG intervention, 17 biomarkers were obviously restored to normal levels. Further metabolic pathway analysis showed that aspartate and glutamate metabolism, arachidonic acid metabolism, arginine and proline metabolism, and TCA cycle were the most related pathways for SDG treatment. Based on these findings, the main mechanisms of SDG against CAG might be attributed to the regulatory effects of energy balance, inflammatory suppression, and improvement in disturbed amino acid and lipid metabolism. This study provided information for the mechanism research of SDG against CAG and would promote its clinical application.

Determination of the protective effects of Hua\u2010Zhuo\u2010Jie\u2010Du in chronic atrophic gastritis by regulating intestinal microbiota and metabolites: combination of liquid chromatograph mass spectrometer metabolic profiling and 16S rRNA gene sequencing

Background Hua-Zhuo-Jie-Du (HZJD), a Chinese herbal prescription consisting of 11 herbs, is commonly used in China to treat chronic atrophic gastritis (CAG). We aimed to determine the effect of HZJD on the microbiome-associated metabolic changes in CAG rats.Methods The CAG rat models were induced by 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) combined with irregular fasting and 2% sodium salicylate, which was intragastrically administrated in fasted animals for 24 weeks. The CAG rats in the Chinese medicine (CM) group were administered a daily dose of 14.81 g/kg/day HZJD, and the vitacoenzyme (V) group were administered a daily dose of 0.08 g/kg/day vitacoenzyme. All animals were treated for 10 consecutive weeks, consecutively. Hematoxylin and eosin (H&E) staining was used to assess the histopathological changes in the gastric tissues. An integrated approach based on liquid chromatograph mass spectrometer (LC-MS) metabolic profiling combined with 16S rRNA gene sequencing was carried out to assess the effects of HZJD on CAG rats. Spearman analysis was used to calculate the correlation coefficient between the different intestinal microbiota and the metabolites.ResultsThe H&E results indicated that HZJD could improve the pathological condition of CAG rats. The LC–MS results indicated that HZJD could significantly improve 21 gastric mucosal tissue perturbed metabolites in CAG rats; the affected metabolites were found to be involved in multiple metabolic pathways, such as the central carbon metabolism in cancer. The results of 16S rRNA gene sequencing indicated that HZJD could regulate the diversity, microbial composition, and abundance of the intestinal microbiota of CAG rats. Following HZJD treatment, the relative abundance of Turicibacter was increased, and the relative abundance of Desulfococcus and Escherichia were decreased in the CM group when compared with the M group. Spearman analysis revealed that perturbed intestinal microbes had a strong correlation with differential metabolites, Escherichia exhibited a negative correlation with l-Leucine, Turicibacter was negatively correlated with urea, and Desulfococcus exhibited a positive correlation with trimethylamine, and a negative correlation with choline.ConclusionsHZJD could protect CAG by regulating intestinal microbiota and its metabolites.

Effect of moxibustion and acupuncture on gastric mucosal cell apoptosis and expression of NF-κB, Bcl-2 in chronic atrophic gastritis rats

To observe the effect of moxibustion and acupuncture on apoptosis in gastric mucosal cell and expression of NF-κB, Bcl-2 in chronic atrophic gastritis (CAG) rats, so as to explore its mechanisms underlying improvement of CAG. Forty-eight male SD rats were randomly divided into normal, model, moxibustion and acupuncture groups, with 12 rats in each group. The CAG model was established by gavage of N-methyl-N'-nitro-N-nitroso-guanidine (MNNG) solution and irregular diet for 12 weeks. Moxibustion or acupuncture was applied to "Zusanli" (ST36) and "Zhongwan" (CV12) for 15 min, once daily for two weeks in the moxibustion or acupuncture group. The histopathological changes of the gastric mucosa were observed by HE staining. The apoptosis index of gastric mucosa was measured by TUNEL method. The gene expression levels of NF-κB and Bcl-2 were detected by real-time PCR. After modeling, the color of gastric mucosa was pale and dark, with low folds and significant bleeding points. The glands in lamina propria were atrophied, arranged disorderly, and the numbers were significantly reduced, with inflammatory cells infiltrated. Those histopathological changes were evidently milder in the moxibustion and acupuncture groups. Compared with the normal group, the apoptosis index, NF-κB and Bcl-2 gene expression of the model group were significantly increased (P<0.01). After the treatment, the apoptosis index, NF-κB and Bcl-2 gene expression were significantly reduced in the moxibustion and acupuncture groups (P<0.05，P<0.01). The NF-κB expression was lower in the acupuncture group than that of moxibustion group (P<0.01). Moxibustion and acupuncture therapy can improve the injury of gastric mucosa in CAG rats, which may be associated with its function in down-regulating the expression of NF-κB and Bcl-2 genes in the gastric mucosa.

Berberine Attenuates Chronic Atrophic Gastritis Induced by MNNG and Its Potential Mechanism.

The purpose of this study was to investigate the therapeutic effect of berberine (BBR) on MNNG-induced chronic atrophic gastritis (CAG) and the possible mechanism of BBR through TGF-β1/PI3K signal pathway. GES-1 were pretreated with MNNG for 2 h before BBR treatment in all procedures. Cell viability was quantified by cell counting kit-8, and GES-1 morphology and proliferation were detected by high content screening (HCS) assay. The rat model of CAG was established by MNNG, and the therapeutic effect of BBR on stomach histopathology and serum supernatant were analyzed in vivo. In addition, the possible mechanism of BBR was further discussed, and the expression of related genes and proteins in TGF-β1/PI3K signal pathway was detected. The results showed that BBR could significantly improve the survival rate and morphological changes of GES-1, improve the gastric tissue injury of CAG rats, and reduce the expression of G-17 and inflammatory factors IL-8, TNF-α, IL-6 and IL-1β. In addition, BBR down-regulated the expression of TGF-β1 axis-related signals such as TGF-β1, PI3K, p-Akt/Akt, p-mTOR/mTOR and P70S6K, and promoted the expression of PTEN, LC3-II and Beclin-1. In Conclusion, BBR can improve CAG which may be closely related to TGF-β1/PI3K signal pathway.

Zuojin Pill ameliorates chronic atrophic gastritis induced by MNNG through TGF-β1/PI3K/Akt axis

Ethnopharmacological relevanceZuojin Pill (ZJP) is a classic prescription composed of Coptis chinensis and Tetradium ruticarpum (A.Juss.) T.G.Hartley, which is often used in the treatment of digestive system diseases. Aim of this studyThe purpose of this study was to explore the therapeutic effect and potential mechanism of ZJP on chronic atrophic gastritis (CAG) induced by MNNG. Materials and methodsThe GES-1 and rat model of CAG was established by MNNG. Detection of cell viability, morphological changes and proliferation of GES-1 by CCK-8 and high content screening (HCS) assay. G-17, IL-8 and TNF-α in rat serum were detected by ELISA kit. The expression of related mRNA and protein on TGF-β1/PI3K/Akt signal axis were detected by RT-PCR and Western blot. ResultsThe results showed that ZJP could significantly improve the GES-1 damage induced by MNNG and improve the gastric histomorphology of CAG rats. The intervention of ZJP could significantly reduce the content of G-17 and inflammatory factors IL-8, TNF- α, IL-6 and IL-1β, inhibit the expression of TGF-β1, PI3K and their downstream signals p-Akt, p-mTOR, P70S6K, and promote the expression level of PTEN, LC3-II and Beclin-1. ConclusionZJP has a good therapeutic effect on CAG induced by MNNG, which may be closely related to the inhibition of TGF-β1/PI3K/Akt signal pathway.

Mitochondria metabonomics of Huangqi Jianzhong Tang against chronic atrophic gastritis.

Huangqi Jianzhong Tang (HQJZ) is a representative prescription used for clinical treatment of chronic atrophic gastritis (CAG) in Chinese medicine. Our previous study had revealed that energy regulation was one of the important mechanisms of HQJZ action against CAG. In this study, ultra-high-performance liquid chromatography coupled with quadrupole-Exactive mass spectrometry (UHPLC-Q-Exactive MS) based metabonomics was used to find the potential mitochondrial biomarkers and metabolic pathways of HQJZ in CAG rats, which focused on a specific organelle (mitochondria) isolated from gastric tissue samples. A total of 16 biomarkers from CAG tissues were identified with 11 of these significantly regulated by HQJZ treatment. These biomarkers was mainly involved in glycine, serine, and threonine metabolism; aminoacyl-tRNA biosynthesis metabolism; and taurine and hypotaurine metabolism. Our results show that HQJZ could protect from CAG by altering the mitochondrial function. These findings deepen our understanding of the mitochondrial metabolic changes that occur with CAG and shine a light on the mechanism of HQJZ.

Urine metabolomics of rats with chronic atrophic gastritis.

To use liquid chromatography-mass spectrometry (LC-MS) to identify endogenous differential metabolites in the urine of rats with chronic atrophic gastritis (CAG). Methylnitronitrosoguanidine (MNNG) was used to produce a CAG model in Wistar rats, and HE staining was used to determine the pathological model. LC-MS was used to detect the differential metabolic profiles in rat urine. Diversified analysis was performed by the statistical method. Compared with the control group, the model group had 68 differential metabolites, 25 that were upregulated and 43 that were downregulated. The main metabolic pathways were D-glutamine and D-glutamic acid metabolism, histidine metabolism and purine metabolism. By searching for differential metabolites and metabolic pathways in the urine of CAG rats, this study provides effective experimental data for the pathogenesis and clinical diagnosis of CAG.

Effects of moxibustion and acupuncture at Zusanli (ST 36) and Zhongwan (CV 12) on chronic atrophic gastritis in rats.

To evaluate the effects of moxibustion and acupuncture of Zusanli (ST 36) and Zhongwan (CV 12) acupoints on chronic atrophic gastritis (CAG) in rats, and to study the mechanisms behind their actions. Forty-four male Sprague-Dawley rats were induced with CAG by intragastric administration of 40% ethanol combined with free drinking of N-methyl-N'nitro-N-nitrosoguanidine and irregular feeding for 12 weeks, followed by daily treatment with moxibustion or acupuncture for 2 weeks. Histopathologic examination, Western blotting of cytokines [epidermal growth factor (EGF), EGF receptor (EGFR), extracellular signal-regulated kinase (ERK), phosphorylated ERK (p-ERK)], and 1H NMR-based metabolic profiling of gastric tissues were used to measure changes related to CAG modeling and treatment. Moxibustion and acupuncture at Zusanli (ST 36) and Zhongwan (CV 12) each relieved CAG-induced abnormalities in histopathology and cytokine expression of ERK and p-ERK. Only moxibustion treatment regulated the expression of EGF and EGFR. Metabolites that were increased in gastric tissue by CAG induction (alanine, nicotinamide adenine dinucleotide phosphate, uracil DNA glycosylase, lactate, glycerol and adenosine) were restored to normal levels after moxibustion treatment; acupuncture treatment only normalized the levels of adenosine monophosphate and glycerol. Our findings suggest that moxibustion or acupuncture at Zusanli (ST 36) and Zhongwan (CV 12) can significantly improve the condition of CAG in rats. These treatments exert their effects on CAG through different mechanisms.

UPLC-Q-TOF/MS-Based Serum and Urine Metabonomics Study on the Ameliorative Effects of Palmatine on Helicobacter pylori-Induced Chronic Atrophic Gastritis.

ObjectiveThe main objective of this study was to investigate the ameliorative effects of Palmatine (Pal) on Helicobacter pylori (H. pylori) induced chronic atrophic gastritis (CAG)MethodBody function, serum biochemical indicators and histopathology were used to evaluate the pharmacodynamics of Pal on CAG rats. The target genes expression levels were verified and assessed by RT-PCR and immunohistochemistry (IHC). Moreover, UPLC-Q-TOF/MS analysis based on urine and serum was performed to identify the potential metabolites in the pathological process of CAG induced by H. pylori. Metabolic pathway analysis was performed to elucidate the metabolic network associated with Pal treatment of CAG.ResultsPal (10, 20, 40 mg/kg/day) significantly restored the body function of CAG rats, reduced the serum biochemical indicators, and maintained the integrity of the gastric mucosal epithelial barrier while alleviated gastric histological damage. Metabolomics analysis shows that the therapeutic effect of Pal on CAG involves 10 metabolites and 10 metabolic pathways, of which the Taurine and hypotaurine metabolism, Glycerophospholipid metabolism and Pentose and glucuronate interconversions are closely related to the gastrointestinal protection of Pal, and these metabolic pathways crosstalk with each other due to the internet hub of citric acid cycle.ConclusionsMetabolomics was used for the first time to identify potential biomarkers of CAG and to illuminate the therapeutic mechanism of Pal on CAG induced by H. pylori. The results provided a new insight for further research on CAG treatment.

Research strategy thoughts about acupuncture-moxibustion treatment of chronic atrophic gastritis by suppressing apoptosis via circular RNA

Chronic atrophic gastritis (CAG) is a common digestive disease in clinic. Previous experimental and clinical studies have shown that acupuncture has a positive effect for CAG. Apoptosis of gastric mucosal tissue has been shown to play an important role in the process of gastric atrophy and possibly further carcinogenesis in CAG, and the circular RNA (circRNA), a novel class of non-coding RNA, has been confirmed to play a regulatory role in the downstream pathway of apoptosis by many stu-dies. Accumulated findings of experimental studies showed that acupuncture and moxibustion interventions could suppress apoptosis of the cultured human gastric mucosal epithelial cells and lower apoptotic index of gastric mucosal cells in CAG rats. Therefore, circRNA is likely to mediate the inhibitory effect of acupuncture and moxibustion on apoptosis of gastric mucosal epithelial cells in CAG. In this paper, we systematically summarized 1) the regulation of circRNA on apoptosis, 2) the apoptosis and pathological mechanism of CAG, 3) the effect of acupuncture on apoptosis, and proposed that circRNA is highly likely to be involved in the positive effect of acupuncture and moxibustion interventions for CAG. It is recommended that researches should further reveal the scientific basis of acupuncture and moxibustion therapies in the treatment of CAG by exploring the role of related circRNAs and their downstream target proteins in the gastric mucosal tissues.

Acupoint catgut embedding improves gastric mucosal injury by down-regulating expression of HIF-1α and VEGF in chronic atrophic gastritis rats

To observe the effect of acupoint catgut embedding on histopathological changes of gastric mucosa and expression of mucosal hypoxia inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) proteins in chronic atrophic gastritis (CAG) rats, so as to explore its mechanisms underlying improvement of CAG. Male SD rats were divided into blank group (n=10) and model group (n=9) and catgut embedment group (n=10). The CAG model was established by free drinking of N-methyl-N'-nitro-N-nitroso-guanidine solution (100 μg/mL) and irregular diet. Catgut embedment was applied to "Zhongwan" (CV12) and bilateral "Zusanli" (ST36) and "Pishu" (BL20), once every 10 days, 6 times in total. Histopathological changes of gastric mucosal tissue were observed under microscope after H.E. staining. The expression of HIF-1α and VEGF proteins in the antrum of stomach was detected by Western blot. H.E. staining showed that compared with the blank group, the number of rats with glandular necrosis, atrophy and mucosal stasis in the model group were increased significantly (P<0.001, P<0.05).Compared with the model group, the number of rats with gland necrosis, atrophy and mucosal stasis in the catgut embedment group were significantly reduced (P<0.01, P<0.05). Western blot displayed that the expression levels of HIF-1α and VEGF proteins were significantly higher in rats with blood stasis and model group than in those without blood stasis and the blank group (P<0.01), and were considerably down-regulated in the catgut embedment group than in the model group (P<0.05, P<0.01). Acupoint catgut embedment can improve the injury of gastric mucosa in CAG rats, which may be associated with its function in down-regulating the expression of HIF-1α and VEGF proteins in the gastric mucosa.

Network pharmacology research of Astragali Radix in treating chronic atrophic gastritis rats based on mitochondrial metabonomics

Astragali Radix (HuangQi), one important traditional Chinese herb, is used for treatment of chronic atrophic gastritis (CAG). To comprehensively evaluate its regulation on CAG, a mitochondria-specific metabonomics was applied to reveal its action on energy metabolism based on ultra high performance liquid chromatography coupled with quadrupole – Exactive mass spectrometry. 16 related metabolites from mitochondria samples were served as potential biomarkers of CAG. Nine out of them were significantly regulated by HuangQi. Combining with network pharmacology, three active components from HuangQi and 3 mitochondrial metabolites exerted better docking abilities with 56 predicted targeted proteins based on SystemsDock, which were involved into multiple biological abnormities including mitochondrion dysfunction. The results demonstrated that mitochondrial energy metabolism played crucial role contributing to HuangQi against CAG, which was one important mechanism of HuangQi.

Effect of heat-sensitive moxibustion at "Zhongwan" (CV 12) on serum GH and PG in chronic atrophic gastritis rats

To observe the effect of heat-sensitive moxibustion at "Zhongwan" (CV 12) on serum growth hormone (GH) and pepsinogen (PG) in chronic atrophic gastritis (CAG) rats, and to explore the potential mechanism of heat-sensitive moxibustion for CAG. A total of 66 male SD rats were randomized into a blank group (12 rats) and a model establishment group (54 rats). No intervention was given in the blank group. Rats in the model establishment group were intervented with compound pathogeny method for 12 weeks to establish CAG model, which were further divided into a model group (11 rats), a vitacoenzyme group (11 rats) and a moxibustion group (22 rats). In the moxibustion group, suspending moxibustion was applied at "Zhongwan" (CV 12) for 40 min. After the intervention of moxibustion, 0.9% sodium chloride solution was given by gavage (2 mL·kg-1·d-1). According to the changes of tail temperature, rats in the moxibustion group were divided into a heat-sensitive moxibustion group (11 rats) and a non-heat-sensitive moxibustion group (8 rats). The vitacoenzyme group was given vitacoenzyme as the same dose by gavage. The intervention was adopted once a day for 28 days. Changes of body weight were observed among the groups. Expressions of serum GH, PGⅠand PGⅡwere detected by ELISA, and the ratio of PGⅠand PGⅡ (PGR) was calculated. The morphological changes of gastric mucosa were observed by macroscopy and light microscope. ①After modeling, the body weight of rats in the model establishment group was lower than the blank group (P<0.01). Compared with the model group, the body weight of rats in the vitacoenzyme group, the heat-sensitive moxibustion group and the non-heat-sensitive moxibustion group was increased after intervention (P<0.05), and there were no significant differences among the intervention groups (P>0.05). ②Under macroscopy and light microscope, gastric tissue of rats after modeling showed dark red and pale gastric mucosa, lower plica and mucosal congestion. The glands of lamina propria were atrophied or disappeared with sparse and disordered arrangement, in which, lymphoid follicles and inflammatory cells could be observed. After intervention, morphology of gastric mucosa was improved in the vitacoenzyme group, the heat-sensitive moxibustion group and the non-heat-sensitive moxibustion group. ③Compared with the blank group, the serum levels of GH, PGⅠ, PGⅡ and PGR were decreased in the model group (P<0.05, P<0.01). Compared with the model group, the serum levels of GH, PGⅠand PGⅡwere increased in the vitacoenzyme group, the heat-sensitive moxibustion group and the non-heat-sensitive moxibustion group (P<0.05, P<0.01), the levels of PGR were increased without statistical difference (P>0.05). Compared with the vitacoenzyme group and the non-heat-sensitive moxibustion group, the serum levels of GH and PGⅠwere increased in the heat-sensitive moxibustion group (P<0.05). Heat-sensitive moxibustion at "Zhongwan" (CV 12) can improve the morphology of gastric mucosa in chronic atrophic gastritis rats, its mechanism may be related to the up-regulation of serum GH and PGⅠ.

Urinary metabolomics research for Huangqi Jianzhong Tang against chronic atrophic gastritis rats based on 1 H NMR and UPLC-Q/TOF MS.

As a traditional Chinese medicine (TCM), Huangqi Jianzhong Tang (HQJZ) has a good efficacy in treating chronic atrophic gastritis (CAG). Our objective was to determine its mechanism based on the urine comprehensive metabolome. In the study, a metabolomic approach was applied to reveal the efficacy of HQJZ on the constructed CAG rats coupled with proton nuclear magnetic resonance (1 H NMR) and ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF MS). The results showed the regulatory effect of HQJZ on urinary metabolism disorder in CAG rats was similar to the positive drug teprenone. Nineteen and 16 potential biomarkers related to CAG were detected by NMR and UPLC-Q/TOF MS, respectively. Thirty-two urine metabolites were significantly regulated by HQJZ treatment. Combined with MetPA and partial least square regression analysis (PLS-RA), three metabolic pathways of valine, leucine and isoleucine, TCA cycle, and glycine, serine and threonine metabolism were the most relevant pathways for HQJZ treatment. The main mechanism of HQJZ might be due to the balance of energy consumption, inflammatory inhibition, improvement of the immune system and oxidative stress on the constructed CAG rats. These findings provided comprehensive metabolic information of TCM by parallel measurements by LC-MS and NMR.