The Efficacy of Chaihu-Guizhi-Ganjiang Decoction on Chronic Non-Atrophic Gastritis with Gallbladder Heat and Spleen Cold Syndrome and Its Metabolomic Analysis: An Observational Controlled Before-After Clinical Trial.

Purpose: The aim of this study was to verify the effectiveness and explore the mechanism of Chaihu-Guizhi-Ganjiang decoction (CGGD) in the treatment of chronic non-atrophic gastritis (CNAG) with gallbladder heat and spleen cold syndrome (GHSC) by metabolomics based on UHPLC-Q-TOF/MS. Patients and Methods: An observational controlled before-after study was conducted to verify the effectiveness of CGGD in the treatment of CNAG with GHSC from January to June 2023, enrolling 27 patients, who took CGGD for 28 days. 30 healthy volunteers were enrolled as the controls. The efficacy was evaluated by comparing the traditional Chinese medicine (TCM) syndrome and CNAG scores, and clinical parameters before and after treatment. The plasma levels of hormones related to gastrointestinal function were collected by ELISA. The mechanisms of CGGD in the treatment of CNAG with GHSC were explored using a metabolomic approach based on UHPLC-Q-TOF/MS. Results: Patients treated with CGGD experienced a statistically significant improvement in TCM syndrome and CNAG scores (p < 0.01). CGGD treatment evoked the concentration alteration of 15 biomarkers, which were enriched in the glycerophospholipid metabolism, and branched-chain amino acids biosynthesis pathways. Moreover, CGGD treatment attenuated the abnormalities of the gastrointestinal hormone levels and significantly increased the pepsinogen level. Conclusion: It was the first time that this clinical trial presented detailed data on the clinical parameters that demonstrated the effectiveness of CGGD in the treatment of CNAG with GHSC patients. This study also provided supportive evidence that CNAG with GHSC patients were associated with disturbed branched-chain amino acid metabolism and glycerophospholipid levels, suggesting that CNAG treatment based on TCM syndrome scores was reasonable and also provided a potential pharmacological mechanism of action of CGGD.

A Natural Peptide from A Traditional Chinese Medicine Has the Potential to Treat Chronic Atrophic Gastritis by Activating Gastric Stem Cells.

Chronic atrophic gastritis (AG) is initiated mainly by Helicobacter pylori infection, which may progress to stomach cancer following the Correa's cascade. The current treatment regimen is H. pylori eradication, yet evidence is lacking that this treatment is effective on later stages of AG especially gastric gland atrophy. Here, using AG mouse model, patient samples, gastric organoids, and lineage tracing, this study unraveled gastric stem cell (GSC) defect as a crucial pathogenic factor in AG in mouse and human. Moreover, a natural peptide is isolated from a traditional Chinese medicine that activated GSCs to regenerate gastric epithelia in experimental AG models and revitalized the atrophic gastric organoids derived from patients. It is further shown that the peptide exerts its functions by stabilizing the EGF-EGFR complex and specifically activating the downstream ERK and Stat1 signaling. Overall, these findings advance the understanding of AG pathogenesis and open a new avenue for AG treatment.

Regulation of intestinal flora in patients with chronic atrophic gastritis by modified Chai Shao Liu Jun Zi decoction based on 16S rRNA sequencing.

Chai Shao Liu Jun Zi decoction (CSLJZD) is an effective Chinese medicine for the treatment of chronic atrophic gastritis (CAG). However, the effect of CSLJZD on the intestinal flora of patients with CAG remains unclear. We used 16S rRNA gene sequencing to investigate the regulatory effects of CSLJZD on intestinal microflora in patients with CAG. Eight patients with CAG were randomly selected as the model group and 8 healthy medical examiners as the control group; the treatment group comprised patients with CAG after CSLJZD treatment. High-throughput sequencing and bioinformatics analysis of the V3V4 region of the 16S rRNA gene of intestinal bacteria obtained from the intestinal isolates of fecal specimens from all participants were performed separately. 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, and the unweighted pair group method with arithmetic mean were used to examine beta diversity. The LEfSe method was used to identify the differentially expressed bacteria. Differential function analysis was performed using PCA based on KEGG function prediction. Rarefaction and species accumulation curves showed that the sequencing data were reasonable. The Chao1 and ACE indices were significantly increased in patients with CAG compared with those in the healthy group. Following CSLJZD and vitacoenzyme treatment, Chao1 and ACE indices decreased. The PCA, non-metric multi-dimensional scaling, and unweighted pair group method with arithmetic mean results showed that the CAG group was distinct from the healthy and treatment groups. The LEfSe results showed that the abundances of the genus Bilophila, family Desulfovibrionaceae, order Desulfovibrionales and genus Faecalibacterium were significantly higher in the healthy group. The abundance of genus Klebsiella, order Deltaproteobacteria, genus Gemmiger, and other genera was significantly higher in the treatment group. Treatment with CSLJZD had a therapeutic effect on the intestinal flora of patients with CAG.

Protoberberine alkaloids: A review of the gastroprotective effects, pharmacokinetics, and toxicity.

BACKGROUND: Stomach diseases have become global health concerns. Protoberberine alkaloids (PBAs) are a group of quaternary isoquinoline alkaloids from abundant natural sources and have been shown to improve gastric disorders in preclinical and clinical studies. The finding that PBAs exhibit low oral bioavailability but potent pharmacological activity has attracted great interest. PURPOSE: This review aims to provide a systematic review of the molecular mechanisms of PBAs in the treatment of gastric disorders and to discuss the current understanding of the pharmacokinetics and toxicity of PBAs. METHODS: The articles related to PBAs were collected from the Web of Science, Pubmed, and China National Knowledge Infrastructure databases using relevant keywords. The collected articles were screened and categorized according to their research content to focus on the gastroprotective effects, pharmacokinetics, and toxicity of PBAs. RESULTS: Based on the results of preclinical studies, PBAs have demonstrated therapeutic effects on chronic atrophic gastritis and gastric cancer by activating interleukin-4 (IL-4)/signal transducer and activator of transcription 6 (STAT6) pathway and suppressing transforming growth factor-beta 1 (TGF-ß1)/phosphoinositide 3-kinase (PI3K), Janus kinase-2 (JAK2)/signal transducers and activators of transcription 3 (STAT3), and mitogen-activated protein kinase (MAPK) pathways. The major PBAs exhibit similar pharmacokinetic properties, including rapid absorption, slow elimination, and low bioavailability. Notably, the natural organ-targeting property of PBAs may account for the finding of their low blood levels and high pharmacological activity. PBAs interact with other compounds, including conventional drugs and natural products, by modulation of metabolic enzymes and transporters. The potential tissue toxicity of PBAs should be emphasized due to their high tissue accumulation. CONCLUSION: This review highlights the gastroprotective effects, pharmacokinetics, and toxicity of PBAs and will contribute to the evaluation of drug properties and clinical translational studies of PBAs, accelerating their transfer from the laboratory to the bedside.

Effectiveness and safety of Moluodan in the treatment of precancerous lesions of gastric cancer: A randomized clinical trial.

OBJECTIVE: To investigate the clinical potential and safety of Moluodan to reverse gastric precancerous lesions. METHODS: Patients aged 18-70 years diagnosed with moderate-to-severe atrophy and/or moderate-to-severe intestinal metaplasia, with or without low-grade dysplasia, and negative for Helicobacter pylori were recruited in this randomized, double-blind, parallel-controlled trial. The primary outcome was the improvement of global histological diagnosis at 1-year follow-up endoscopy using the operative link for gastritis assessment, the operative link for gastric intestinal metaplasia assessment, and the disappearance rate of dysplasia. RESULTS: Between November 3, 2017 and January 27, 2021, 166 subjects were randomly assigned to the Moluodan group, 168 to the folic acid group, 84 to the combination group, and 84 to the high-dose Moluodan group. The improvement in global histological diagnosis was achieved in 60 (39.5%) subjects receiving Moluodan, 59 (37.8%) receiving folic acid, 26 (32.1%) receiving the combined drugs, and 36 (47.4%) receiving high-dose Moluodan. Moluodan was non-inferior to folic acid (95% confidence interval: -9.2 to 12.5; P = 0.02). High-dose Moluodan had a trend for better protective efficacy, though there was no statistical significance. The disappearance rate of dysplasia was 82.8% in the Moluodan group, which was superior to folic acid (53.9%; P = 0.006). No drug-related serious adverse events were observed. CONCLUSIONS: One pack of Moluodan three times daily for 1 year was safe and effective in reversing gastric precancerous lesions, especially dysplasia. Doubling its dose showed a better efficacy trend.

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.

Study of Helicobacter pylori infection in patients with chronic atrophic gastritis and its relationship with lifestyle habits and dietary nutrient intake: A retrospective analysis.

To explore Helicobacter pylori (Hp) infection status and its relationship with lifestyle habits and dietary factors in patients with chronic atrophic gastritis. Six hundred thirty-eight patients with chronic atrophic gastritis, who were admitted to our hospital from March 2021 to April 2023, were selected for the study. All patients underwent the 13C urea breath test. The relationship between the detection rate of Hp infection and the clinical characteristics, lifestyle habits, and dietary factors of the patients was analyzed. Among the 638 patients with chronic atrophic gastritis, 531 patients were tested positive for Hp infection, the positive rate for Hp infection was approximately 83.23%. Analyzing the clinical characteristics of the patients, it was found that age, family history of gastric cancer, degree of chronic inflammation, degree of glandular atrophy, presence of low-grade dysplasia, and intestinal metaplasia all have an impact on the positive detection rate of patients (P < .05). Analyzing the patients' lifestyle habits, it was found that BMI, smoking history, alcohol consumption, preference for spicy food, dining location, consumption of pickled foods, frequent consumption of grilled/barbecued foods, preference for strong tea, consumption of sweets, and work-related stress had an impact on the positive rate of Hp infection in patients (P < .05). The discovery showed that the levels of total protein, albumin, hemoglobin, cholesterol, and the intake of livestock and poultry meat, seafood, dairy products, vegetables, fruits, and fats have an impact on the positivity rate of Hp infection in patients (P < .05). A multiple logistic regression analysis was performed, and it was found that patients' age, family history of gastric cancer, degree of chronic inflammation, degree of glandular atrophy, presence of low-grade dysplasia, presence of wasting or obesity, history of alcohol consumption, preference for spicy food, dining location, frequent consumption of strong tea, high work pressure, high intake of fish and seafood, low intake of dairy products, low intake of vegetables, low intake of fruits, and low intake of fats all had an impact on the occurrence of Hp infection in patients (P < .05). There is a certain correlation between patients' lifestyle habits, dietary factors, and clinical characteristics with the occurrence of Hp infection. These factors can assist in the prevention of Hp infection.

Mechanistic insights into the ameliorative effects of Xianglianhuazhuo formula on chronic atrophic gastritis through ferroptosis mediated by YY1/miR-320a/TFRC signal pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Xianglianhuazhuo formula (XLHZ) has a potential therapeutic effect on chronic atrophic gastritis (CAG). However, the specific molecular mechanism remains unclear. AIM OF THE STUDY: To evaluate the effect of XLHZ on CAG in vitro and in vivo and its potential mechanisms. METHODS: A rat model of CAG was established using a composite modeling method, and the pathological changes and ultrastructure of gastric mucosa were observed. YY1/miR-320a/TFRC and ferroptosis-related molecules were detected. An MNNG-induced gastric epithelial cell model was established in vitro to evaluate the inhibitory effect of XLHZ on cell ferroptosis by observing cell proliferation, migration, invasion, apoptosis, and molecules related to ferroptosis. The specific mechanism of action of XLHZ in treating CAG was elucidated by silencing or overexpression of targets. RESULTS: In vivo experiments showed that XLHZ could improve the pathological status and ultrastructure of gastric mucosa and inhibit ferroptosis by regulating the YY1/miR-320a/TFRC signaling pathway. The results in vitro demonstrated that transfection of miR-320a mimics inhibited cell proliferation, migration, and invasion while promoting cell apoptosis. MiR-320a targeted TFRC and inhibited ferroptosis. Overexpression of TFRC reversed the inhibitory effect of miR-320a overexpression on cell proliferation. The effect of XLHZ was consistent with that of miR-320a. YY1 targeted miR-320a, and its overexpression promoted ferroptosis. CONCLUSION: XLHZ inhibited ferroptosis by regulating the YY1/miR-320a/TFRC signaling pathway, ultimately impeding the progression of CAG.

Effects of oxidative stress regulation in inflammation-associated gastric cancer progression treated using traditional Chinese medicines: A review.

Gastric cancer (GC) is a global public health concern that poses a serious threat to human health owing to its high morbidity and mortality rates. Due to the lack of specificity of symptoms, patients with GC tend to be diagnosed at an advanced stage with poor prognosis. Therefore, the development of new treatment methods is particularly urgent. Chronic atrophic gastritis (CAG), a precancerous GC lesion, plays a key role in its occurrence and development. Oxidative stress has been identified as an important factor driving the development and progression of the pathological processes of CAG and GC. Therefore, regulating oxidative stress pathways can not only intervene in CAG development but also prevent the occurrence and metastasis of GC and improve the prognosis of GC patients. In this study, PubMed, CNKI, and Web of Science were used to search for a large number of relevant studies. The review results suggested that the active ingredients of traditional Chinese medicine (TCM) and TCM prescriptions could target and improve inflammation, pathological status, metastasis, and invasion of tumor cells, providing a potential new supplement for the treatment of CAG and GC.

Clinical Efficacy of Diet Intervention Combined with Bismuth Potassium Citrate in Helicobacter pylori-Related Chronic Atrophic Gastritis.

Objective: To investigate the clinical impact of dietary intervention in combination with bismuth potassium citrate in the management of chronic atrophic gastritis (CAG) caused by Helicobacter pylori. Methods: From April 2019 to October 2022, 160 patients with newly identified Helicobacter pylori-related CAG were treated at our facility. They were split into two groups at random: the bismuth potassium citrate medication group (n = 80) and the diet intervention + bismuth potassium citrate experimental groups (n = 80). The bismuth potassium citrate treatment group was given bismuth potassium citrate capsule treatment only, and the diet intervention + bismuth potassium citrate treatment group was given diet intervention based on bismuth potassium citrate capsule. The diet intervention score, symptom score, and pathological score of the two groups were observed at baseline and after treatment, and the relationship between dietary intervention and symptoms and pathology of Helicobacter pylori-related CAG was analyzed. Results: During the baseline period, there was no discernible difference in the diet intervention score, symptom score, or pathology score between the two groups (P > .05); after the diet intervention combination treatment, the diet intervention score, diet intervention + bismuth potassium citrate experimental groups symptom score, and pathology score were considerably lower than those in the bismuth potassium citrate treated group (P < .05). Conclusions: Dietary intervention combined with bismuth potassium citrate exhibited more effective treatment than bismuth potassium citrate-only treatment in Helicobacter pylori-related CAG, which hinted us proper diet has a positive impact on improving the therapeutic efficacy of bismuth potassium citrate.

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

BACKGROUND: Cinnamomi 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. PURPOSE: This study aimed to explore its mechanism against CAG based on amalgamated strategies. METHODS: Network 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. RESULTS: Network 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. CONCLUSION: Our 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.

Experimental validation for mechanisms of Qizhiweitong particles against Chronic Non-atrophic gastritis based on metabolomics and network pharmacology.

Qizhiweitong particles (QZWT), a classic Chinese herbal prescription derived from the Sinisan decoction in Shang Han Za Bing Lun, has definitive clinical efficacy in treating Chronic Non-atrophic Gastritis (CNG) in China. However, its mechanism of action at the metabolic level remains unclear. The aim of this study was to explore the mechanisms of QZWT against CNG based on non-targeted metabolomics combined with network pharmacology and experimentally validated by enzyme linked immunosorbent assays (ELISA). First, CNG model rats were established by free drinking ammonia water combined with starvation and satiety disorder for 12 weeks. Taking gastric tissue as the object, ultra-high performance liquid chromatography tandem mass spectrometry based metabolomics and network pharmacology were conducted to identify the key compounds, core targets and pathways that mediate the effects of QZWT against CNG. Furthermore, the targets from network pharmacology and the metabolites from metabolomics were jointly analyzed to select crucial metabolism pathways by MetaScape. Finally, the key metabolic enzymes and metabolites were experimentally validated by ELISA. The results indicated that there were 29 differential metabolites were identified and considered to be metabolic biomarkers of QZWT in the treatment of CNG. Among them, 8 of the differential metabolites showed a significant reduction in the content of QZWT groups. Arachidonic acid (AA) metabolic and glycerophospholipid (GP) metabolic are the most crucial metabolic pathways for QZWT to treat CNG. QZWT regulated AA and GP metabolism by synergetic reducing the level of AA, Phospholipid acid and Lysophosphatidic acid and inhibiting the enzyme activity of prostaglandin endoperoxide synthase 1 and prostaglandin endoperoxide synthase 2. And a compound-reaction-enzyme-gene network of mechanism for QZWT against CNG was established. In conclusion, this study reveals the complicated mechanisms of QZWT against CNG. Our work presents a novel strategy to identify the potential mechanisms of pharmacological effects derived from a compound prescription of TCM.

Effects of folic acid supplementation on chronic atrophic gastritis based on MTHFR C677T polymorphism.

BACKGROUND: It has been shown the methylenetetrahydrofolate reductase (MTHFR) 677TT (rs 1801133) genotype predicts histopathological alterations in the incisura of patients with chronic atrophic gastritis (CAG). MTHFR is a crucial enzyme in fatty acid (FA) metabolism. This study aimed to evaluate the influence of FA supplementation in CAG patients without Helicobacter pylori infection and the MTHFR C677T (rs 1801133) genotype as a potential CAG predictor. METHODS: A total of 96 CAG patients, aged 21 to 72 years old, were enrolled in this study. After 6 months of treatment, histopathological outcomes were compared among patients treated with weifuchun (WFC) (1.44 g 3 times per os per day), those treated with WFC and FA (5 mg once daily), and those treated with WFC, FA, and vitamin B12 (VB12) (0.5 mg 3 times per day) based on the Operative Link on Gastritis/Intestinal Metaplasia assessment staging systems. RESULTS: Atrophic lesions in patients treated with WFC and FA improved more than in patients treated only with WFC therapy (78.1% vs 53.3%, P = .04). Atrophic or intestinal metaplasia (IM) lesions in the incisura of patients with the TT genotype were better than those in patients with the CC/CT genotype (P = .02). CONCLUSION: The treatment of CAG patients with 5 mg of FA supplements daily for 6 months improved their gastric atrophy status, especially for the Operative Link on Gastritis/Intestinal Metaplasia assessment stages I/II. Moreover, our study is the first to reveal that patients with the MTHFR 677TT genotype require more timely and effective FA treatment than those with the CC/CT genotype.

Tibetan medicine Liuwei Muxiang pills (LWMX pills) effectively protects mice from chronic non-atrophic gastritis.

BACKGROUND: Chronic non-atrophic gastritis (CNG) is the most common type of chronic gastritis. If not actively treated, it may induce gastric cancer (GC). Western medicine is effective in CNG, but there are more adverse reactions after long-term medication, and it is easy to relapse after treatment, which affects patients' health and life. Tibetan medicine Liuwei Muxiang Pills (LWMX pills) is a traditional Tibetan medicine compound, which has a unique curative effect in the treatment of gastric inflammation, especially chronic non-atrophic gastritis. However, the mechanisms of LWMX pills for treatment CNG still remain poor known. PURPOSE: The aim of this study was to evaluate the therapeutic intervention potential of Tibetan medicine LWMX pills on CNG and explore its potential mechanisms in mice models. METHODS: The mice models was established to evaluate the therapeutic effect of LWMX pills on CNG. The main components of LWMX pills were analyzed by GC-MS. HE staining, immunohistochemistry, proteomics and Western Blot were used to analyze the potential mechanism of LWMX pills for CNG treatment. RESULTS: In the present study, LWMX pills containing costunolide, dehydrocostuslactone and antioxidants were found. IF results showed that the expression of ALDH1B1 in the control group was significantly lower than that in the model group in the gastric mucosa tissue, and the expression of ALDH1B1 was significantly lower in the 25 mg/ml LWMX Pills group (one month) and 25 mg/ml LWMX Pills group (two months) than in the model group. IHC revealed that model group samples expressed higher levels of Furin than 25 mg/ml LWMX Pills group samples, as evidenced by very strong staining of Furin in gastric mucosal cells. However, AMY2 staining in gastric mucosal cells did not differ significantly between the treated and control groups. the protein expression levels of these proteins were decreased in 25 mg/mL LWMX pills. Meanwhile, we found that the CAM1 protein expression in the in 25 mg/ml LWMX pills group (two mouths) was increased compared to the in 25 mg/ml LWMX pills group (one mouths).Western blotting showed that the protein expression levels of Furin, AMY2A, CPA3, ALDH1B1, Cam1, COXII, IL-6, IL-1ß were decreased in 25 mg/mL LWMX pills. Meanwhile, that the CAM1 protein expression in the in 25 mg/ml LWMX pills group (two mouths) was increased compared to the in 25 mg/ml LWMX pills group (one mouths). CONCLUSION: 25mg/ml LWMX pill treatment for one month had better therapeutic effect on mice CNG. Further proteomic results showed that LWMX pills maintain gastric function by inhibiting inflammation and oxidative stress, and we also found that LWMX pills regulate the expression of proteins associated with cancer development (Amy2, Furin).

Efficacy and safety of Weifuchun tablet for chronic atrophic gastritis: A systematic review and meta-analysis.

BACKGROUND: Chronic atrophic gastritis is a significant premalignant lesion of gastric carcinoma. There is a great need to prevent the progression to gastric carcinoma through early intervention and treatment for chronic atrophic gastritis. Weifuchun, a famous Chinese patent drug, has been widely used for chronic atrophic gastritis in China. However, it remains unclear whether Weifuchun is effective for atrophic gastritis. OBJECTIVE: To determine the effectiveness and safety of Weifuchun for chronic atrophic gastritis. METHODS: We systematically retrieved seven databases (Cochrane Library, EMBASE, PubMed, China National Knowledge Infrastructure, Wanfang database, Chinese Scientific Journals Database, and Chinese Biological Medical Database) from their inception to October 5, 2022. Methodological quality was examined using the Cochrane Risk of bias tool. We also used RevMan 5.4 software for statistical analysis to examine the effectiveness and safety of Weifuchun. RESULTS: Fifteen studies with 1,488 patients were enrolled in this meta-analysis. The study indicated that Weifuchun was more effective (RR 1.52; 95% CI 1.41, 1.63; p<0.00001) than Western medicine and other Chinese patent medicine. In addition, Weifuchun was more effective in improving gastric mucosal under gastroscopy, improving histopathologic changes of gastric mucosal, and inhibiting Helicobacter pylori. However, no significant difference in safety was examined between Weifuchun and the control group (RR 2.83; 95% CI 0.85, 9.38; P = 0.09). CONCLUSIONS: The meta-analysis revealed a significant statistical difference with Weifuchun in effectiveness compared to the control group. However, there was no significant difference in safety. Thus, more high-quality clinical studies are needed in the future. TRIAL REGISTRATION: Registration number CRD42022365703.

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

BACKGROUND: As 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. PURPOSE: The purpose of this study was to investigate the mechanism of XJZ against CAG rats via gut microbiome using a multi-omics approach. METHODS: The 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. RESULTS: A 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. CONCLUSION: The 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.

A Randomized Double-blind Clinical Trial of Weierkang Pills for the Treatment of Chronic Atrophic Gastritis.

BACKGROUND AND GOALS: There are currently no standard treatments for chronic atrophic gastritis and traditional Chinese medicine may be effective. This study aims to investigate the efficacy and safety of Weierkang pills in treating chronic atrophic gastritis. MATERIALS AND METHODS: There were 108 patients in our study. They were randomly assigned to 2 groups. In group A, patients received Weierkang pills and patients in group B received folic acid combined with teprenone. Symptoms, endoscopic scores, and biopsy specimens were compared at baseline and 3 months after treatment. Meanwhile, the expressions of vascular endothelial growth factor and trefoil factor 3 (TFF3) in biopsy specimens were also compared. RESULTS: Our study showed that the total effective rates of atrophy/intestinal metaplasia in group A reached the same level as group B (51.7% vs. 40.0%, P =0.419). Weierkang significantly improved the total effective rate of atrophy/intestinal metaplasia in gastric angle compared with group B (64.7% vs. 33.3%, P =0.024). Weierkang can significantly lower the total Kyoto risk score (2.6±1.1 vs. 3.3±1.0, P =0.002) and atrophy score (1.4±0.6 vs. 1.8±0.5, P =0.001) after treatment. In addition, Weierkang improves symptoms (1.3±1.3 vs. 2.3±1.8, P =0.003) and epigastric pain (0.2±0.4 vs. 0.5±0.6, P =0.041). The expression of TFF3 in gastric mucosa decreased significantly after treatment with Weierkang ( P =0.002). CONCLUSIONS: Weierkang can improve the endoscopic appearance and pathologic changes of chronic atrophic gastritis patients. Symptoms also improved. TFF3 may be involved the pathophysiology mechanism.

Medicine for chronic atrophic gastritis: a systematic review, meta- and network pharmacology analysis.

PURPOSE: The aim of this study is to determine the effectiveness and reliability of adding traditional Chinese medicine (TCM) in the clinical intervention and explore mechanisms of action for chronic atrophic gastritis (CAG) through meta- and network pharmacology analysis (NPAs). METHODS: A predefined search strategy was used to retrieve literature from PubMed, Embase database, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Database (CBM), Wan Fang Data and China Science and Technology Journal Database (VIP). After applying inclusion and exclusion criteria, a total of 12 randomized controlled trials (RCTs) were included for meta-analysis to provide clinical evidence of the intervention effects. A network meta-analysis using Bayesian networks was conducted to observe the relative effects of different intervention measures and possible ranking of effects. The composition of the TCM formulation in the experimental group was analysed, and association rule mining was performed to identify hub herbal medicines. Target genes for CAG were searched in GeneCards, Online Mendelian Inheritance in Man, PharmGKB, Therapeutic Target Database and DrugBank. A regulatory network was constructed to connect the target genes with active ingredients of the hub herbal medicines. Enrichment analyses were performed using the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to examine the central targets from a comprehensive viewpoint. Protein-protein interaction networks (PPINs) were constructed to identify hub genes and conduct molecular docking with differentially expressed genes (DEGs) and corresponding active molecules. RESULTS: A total of 1140 participants from 12 RCTs were included in the statistical analysis, confirming that the experimental group receiving the addition of TCM intervention had better clinical efficacy. Seven hub TCMs (Paeonia lactiflora, Atractylodes macrocephala, Pinellia ternata, Citrus reticulata, Codonopsis pilosula, Salvia miltiorrhiza and Coptis chinensis) were identified through association rule analysis of all included TCMs. Thirteen hub genes (CDKN1A, CASP3, STAT1, TP53, JUN, MAPK1, STAT3, MAPK3, MYC, HIF1A, FOS, MAPK14 and AKT1) were obtained from 90 gene PPINs. Differential gene expression analysis between the disease and normal gastric tissue identified MAPK1 and MAPK3 as the significant genes. Molecular docking analysis revealed that naringenin, luteolin and quercetin were the main active compounds with good binding activities to the two hub targets. GO analysis demonstrated the function of the targets in protein binding, while KEGG analysis indicated their involvement in important pathways related to cancer. CONCLUSIONS: The results of a meta-analysis of 12 RCTs indicate that TCM intervention can improve the clinical treatment efficacy of CAG. NPAs identified seven hub TCM and 13 target genes associated with their actions, while bioinformatics analysis identified two DEGs between normal and CAG gastric tissues. Finally, molecular docking was employed to reveal the mechanism of action of the active molecules in TCM on the DEGs. These findings not only reveal the mechanisms of action of the active components of the TCMs, but also provide support for the development of new drugs, ultimately blocking the progression from chronic gastritis to gastric cancer.

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. AIM: To determine the effect of GD treatment on CAG and its potential cellular mechanism. METHODS: A 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. RESULTS: The 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). CONCLUSION: Treatment 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.

Mechanisms of Banxia Xiexin Decoction Underlying Chronic Atrophic Gastritis via Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulations.

Chronic atrophic gastritis (CAG) is a common chronically digestive disease which is notoriously characterized by atrophy of the epithelium and glands of the gastric mucosa, reduced number, thinning of the gastric mucosa, thickening of the mucosal base, or pyloric glandular hyperplasia and intestinal glandular hyperplasia, or with atypical hyperplasia. Banxia Xiexin decoction (BXD) has been applied for two thousand years and is considered an effective therapy for functional dyspepsia, gastroesophageal reflux disease and colon cancer. In this current study, to probe into the underlying mechanism of BXD on CAG, network pharmacology was conducted to collect druggable ingredients and predicted targets of BXD and the CAG-associated targets were harvested to take intersection with druggable ingredients from BXD predicted targets to obtain potential critical action targets. Subsequently, GO enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were conducted to elucidate the underlying mechanisms and roles from the perspective of overall pathways and cellular functions. Eventually, molecular docking integrated with molecular dynamics simulations was conducted to further investigate the mechanism of action of BXD active ingredients on CAG from drug molecule-target interactions and to provide a theoretical basis for BXD drug development.