Weifuchun suppresses the malignancy of gastric cancer cells by targeting KPNA2 through miR-26a-5p-mediated destabilization and the deactivation of the MAPK signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Weifuchun (WFC) is a Traditional Chinese Medicine commonly used for treating atrophic gastritis and intestinal metaplasia. Till date, its antitumor effect on gastric cancer (GC) and the underlying mechanisms of the effect remains unelucidated. AIM OF THE STUDY: We aim to investigate if WFC can suppress the malignancy of stomach cancer cells and dissect the molecular basis and the associated molecular and cellular features. MATERIALS AND METHODS: Stomach cancer cell lines and normal gastric epithelial cells were treated with WFC. CCK8 assay, caspase-3 activity assay, adhesion assay, microRNA database analysis, transfection, RT-PCR, Western Blotting, signaling pathway analysis, and in vivo GC model were employed to examine the changes in the features of the gastric cancer cells and the molecular mechanisms of the effect of WFC. RESULTS: Here we present data demonstrating that WFC suppresses the malignant cellular phenotypes of GC and this inhibitory effect is mediated by downregulating the expression of oncogenic KPNA2. Furthermore, WFC downregulates KPNA2 through miR-26a-5p-mediated gene silencing and the deactivated phosphorylation dynamics of mitogen-activated protein kinase (MAPK). The suppressive effect of WFC on stomach cancer cell behavior was further confirmed in animal model. CONCLUSION: Therefore, WFC can exert inhibitory effect on the malignancy of GC cells by reducing the levels of KPNA2. Moreover, the miR-26a-5p rescue and the deactivation MAPK pathway induced by WFC result in the downregulation of KPNA2 expression. Thus, our findings suggest WFC as a potential treatment option against GC.

Yiwei Xiaoyu granules for treatment of chronic atrophic gastritis with deficiency syndrome of the spleen and stomach.

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

Exploring the effect of Weifuchun capsule on the toll-like receptor pathway mediated HES6 and immune regulation against chronic atrophic gastritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Weifuchun capsule (WFC) is a traditional Chinese patent medicine for chronic atrophic gastritis (CAG) in clinic. However, the mechanism of action of WFC for CAG still remains unclear due to its complex composition. AIM OF THE STUDY: The study was projected to uncover the mechanism of action of WFC and the corresponding pharmacodynamic substance of WFC against CAG as well as providing a standard example for the research of traditional Chinese medicine (TCM) from the perspective of the network and the system. MATERIALS AND METHODS: We identified the compounds of WFC through LC-MS/MS analysis and performed a systematic network targets analysis for WFC in the treatment of CAG which thoroughly described the mechanism of action of WFC for CAG. Based on analysis integrating omics data and algorithms, we focused on the specific immune regulatory role of WFC in the treatment of CAG, especially on a hub pathway, Toll-like receptor signaling pathway and thus deciphered the role of WFC in immune regulation, anti-inflammation and mediation of HES6. In experiments part, MNNG-GES-1-cell line and rat models were used to validate our findings. RESULTS: In this study, compounds of WFC are identified through LC‒MS/MS and network target analysis is performed to dissect the specific immunoregulatory effect as well as mediation of HES6, a newly discovered biomolecule related to gastritis carcinoma progression, of WFC on CAG through the Toll-like receptor signaling pathway. Based on cell line and rat models, we verify the mechanism of action of WFC for CAG in inhibiting inflammatory cytokines, regulating immune cells like T cells and macrophages, related genes including TLR2 and CD14. It is also validated that WFC inhibits the expression of HES6 (P < 0.05). CONCLUSION: Based on the combination of computational strategy and experiments, our study offers a comprehensive analysis to reveal the role of WFC in regulating immune response, inhibiting inflammation in the treatment of CAG, and provides a standard example for the research of TCM from the perspective of the network and the system.

Clinical efficacy of Weisu granule combined with Weifuchun tablet in the treatment of chronic atrophic gastritis and its effect on serum G-17, PG I and PG II levels.

OBJECTIVE: The aim of this prospective study was to explore the clinical efficacy of Weisu granules combined with Weifuchun tablets in the treatment of chronic atrophic gastritis and its effect on serum gastrin-17 (G-17), pepsinogen I (PG I), and II (PG II) levels. METHODS: Totally, 120 patients with chronic atrophic gastritis admitted to our hospital from February 2019 to February 2020 were enrolled and randomized into a control group (n=60) treated with Weifuchun tablets, and a experimental group given Weisu granules. Serum G-17, PG I, and PG II levels, inflammatory factor levels, TCM syndrome scores, gastric mucosa pathological scores, and clinical efficacy were compared between the two groups. Gastric tissue changes were observed using gastroscopy and HE staining. RESULTS: After treatment, the levels of serum G-17, PG I, and PG II of the experimental group were significantly better than those of the control group (P<0.001). The levels of inflammatory factors, traditional Chinese medicine (TCM) syndrome scores, and gastric mucosal pathology scores of the experimental group were significantly lower than those of the control group (P<0.001). The overall response rate of the experimental group was significantly higher than that of the control group (P<0.05). The experimental group showed a lower HP positive result and a higher HP negative conversion ratio than the control group (all P<0.05). HE staining results revealed that after treatment, the number of glands was basically restored to the level of normal gastric mucosa, and the improvement of inflammatory cell infiltration in the experimental group was significantly better than that in the control group. CONCLUSION: Weisu granule combined with Weifuchun tablets can ameliorate serum G-17, PG I, and PG II levels in patients with chronic atrophic gastritis, relieve inflammatory responses and clinical symptoms, and improve the treatment effect, which is worth promoting in clinical practice. CLINICAL TRIAL REGISTRATION: Chinese Registry of Clinical Trials. TRIAL REGISTRATION NUMBER: ChiCTR200002548416. Trial URL: http://www.chictr.org.cn/showproj.aspx?proj=26516901.

A correlational study of Weifuchun and its clinical effect on intestinal flora in precancerous lesions of gastric cancer.

BACKGROUND: Weifuchun (WFC), a Chinese herbal prescription consisting of Red Ginseng, Isodon amethystoides and Fructus Aurantii, is commonly used in China to treat a variety of chronic stomach disorders. The aim of the paper was to determine the effect of WFC on intestinal microbiota changes in precancerous lesions of gastric cancer (PLGC) patients. METHODS: PLGC patients of H. pylori negative were randomly divided into two groups and received either WFC tablets for a dose of 1.44 g three times a day or vitacoenzyme (Vit) tablets for a dose of 0.8 g three times a day. All patients were treated for 6 months consecutively. Gastroscopy and histopathology were used to assess the histopathological changes in gastric tissues before and after treatment. 16S rRNA gene sequencing was carried out to assess the effects WFC on intestinal microbiota changes in PLGC patients. Receiver Operating Characteristics (ROC) analysis was used to assess the sensitivity and specificity of different intestinal microbiota in distinguishing between PLGC patients and healthy control group. RESULTS: Gastroscopy and histopathological results indicated that WFC could improve the pathological condition of PLGC patients, especially in the case of atrophy or intestinal metaplasia. The results of 16S rRNA gene sequencing indicated that WFC could regulate microbial diversity, microbial composition, and abundance of the intestinal microbiota of PLGC patients. Following WFC treatment, the relative abundance of Parabacteroides decreased in WFC group when compared with the Vit group. ROC analysis found that the Parabacteroides could effectively distinguish PLGC patients from healthy individuals with sensitivity of 0.79 and specificity of 0.8. CONCLUSIONS: WFC could slow down the progression of PLGC by regulating intestinal microbiota abundance. Trial registration NCT03814629. Name of registry: Randomized Clinical Trial: Weifuchun Treatment on Precancerous Lesions of Gastric Cancer. Registered 3 August 2018-Retrospectively registered, https://register.clinicaltrials.gov/ NCT03814629.

A Combined Phytochemistry and Network Pharmacology Approach to Reveal the Effective Substances and Mechanisms of Wei-Fu-Chun Tablet in the Treatment of Precancerous Lesions of Gastric Cancer.

Wei-Fu-Chun (WFC) tablet is a commercial medicinal product approved by China Food and Drug Administration, which is made of Panax ginseng C.A.Mey., Citrus aurantium L., and Isodon amethystoides (Benth.). WFC has been popularly used for the treatment of precancerous lesions of gastric cancer (PLGC) in clinical practice. In this study, a UHPLC-ESI-Q-TOF/MS method in both positive and negative ion mode was employed to rapidly survey the major constituents of WFC. 178 compounds including diterpenoids, triterpenes, sesquiterpenes, flavonoids, saponins, phenylpropanoids, lignans, coumarins, organic acids, fatty acids, quinones, and sterols, were identified by comparing their retention times, accurate mass within 5 ppm error, and MS fragmentation ions. In addition, 77 absorbed parent molecules and nine metabolites in rat serum were rapidly characterized by UHPLC-ESI-Q-TOF/MS. The network pharmacology method was used to predict the active components, corresponding therapeutic targets, and related pathways of WFC in the treatment of PLGC. Based on the main compounds in WFC and their metabolites in rat plasma and existing databases, 13 active components, 48 therapeutic targets, and 61 pathways were found to treat PLGC. The results of PLGC experiment in rats showed that WFC could improve the weight of PLGC rats and the histopathological changes of gastric mucosa partly by inhibiting Mitogen-activated protein kinase (MAPK) signaling pathway to increase pepsin secretion. This study offers an applicable approach to identify chemical components, absorbed compounds, and metabolic compounds in WFC, and provides a method to explore bioactive ingredients and action mechanisms of WFC.

A Review of Therapeutic Effects and the Pharmacological Molecular Mechanisms of Chinese Medicine Weifuchun in Treating Precancerous Gastric Conditions.

Patients with precancerous gastric conditions are at a high risk for gastric carcinoma. The Chinese medicine Weifuchun (WFC) is used in treating chronic superficial gastritis and in postoperative adjuvant treatment of gastric cancer. Both monotherapy and combination therapy of WFC with other drugs can result in a favorable therapeutic outcome. WFC can dramatically improve clinical outcomes in patients with gastric precancerous lesions by targeting multiple pathways including pathways involved in the pharmacological action of Radix Ginseng Rubra (red ginseng), Rabdosia amethystoides, and fried Fructus Aurantii, including regulation of NF-κB, RUNX3/TGF-beta/Smad, Hedgehog (Hh) and Wnt signaling pathways, modulation of the expression of oncogenes and tumor suppressor genes, and indirect inhibition of Helicobacter pylori (Hp) by maintaining gastric microbial ecosystem. In this review, we will discuss the clinical efficacy and therapeutic regimen of WFC for gastric precancerous lesions and the molecular mechanisms involved. This review will highlight WFC-based therapeutic strategies in disrupting progress to gastric cancer and provide more information on the pharmacological mechanisms of WFC and its clinical application for the treatment of precancerous gastric lesions.

The curative effect of Fuzhengxiaojia decoction on precancerous lesions of gastric cancer / 西安交通大学学报(医学版)

Objective To observe the curative effect of Fuzhengxiaojia decoction on precancerous lesion of gastric cancer (PLGC).Methods We randomly divided 44 patients with PLGC in our hospital into control group (n=22)and treatment group (n=22).The control group was given 4 Weifuchun tablets each time and three times per day and while the treatment group was given one Fuzhengxiaojia decoction of 400 mL besides the medication of the control group.They were treated for two courses,one course lasting for one month.Results Superoxide dismutase (SOD),malondialdehyde (MDA),glutathione peroxidase (GSH-Px),IgG,IgM and IgA in the two groups had no significant differences before treatment (P＞0.05).After treatment,compared with those in the control group,SOD (t=2.144,P=0.044)and GSH-Px (t=2.322,P=0.030)increased,while MDA(t=3.096, P=0.005),IgG(t=2.421,P=0.025),IgM(t=3.377,P=0.003)and IgA (t=2.521,P=0.020)decreased. The main symptom scores in the two groups did not significantly differ before treatment (P＜0.05).After treatment, compared with those in the control group,the scores for main symptoms like reduced food intake (t=3.924,P＜0.001),stomach noise (t=4.161,P＜0.001)and gastric or hypochondriac swelling (t=2.881,P＜0.009) decreased in the treatment group.The rate of effective cases was higher than that in the control group (χ2=4.539, P=0.033).Conclusion The effect of Weifuchun combined with Fuzhengxiaojia prescriptions in treating PLGC is better than Weifuchun alone,which is related to improving redox and immunoglobulin.

Clinical Efficacy of Weipixiao in Treating Chronic Atrophic Gastritis / 广州中医药大学学报

Objective To investigate the clinical curative effect of Weipixiao for the treatment of chronic atrophic gastritis (CAG). Methods A total of 58 CAG patients with spleen-stomach deficiency syndrome was evenly randomized into Weipixiao group and Weifuchun group. Weipixiao group was treated with Weipixiao decoction orally,and Weifuchun group was treated with Weifuchun tablets orally. The treatment time covered 12 weeks. The scores of symptoms and pathology of CAG patients were graded before and after treatment. The clinical efficacy was evaluated with the symptom scores and pathological scores. Results (1)The scores of primary symptoms and secondary symptoms in the two groups were obviously decreased after treatment (P < 0.05 compared with those before treatment),and the decrease in Weipixiao group was superior to that in Weifuchun group(P< 0.05).(2) The total effective rate for clinical efficacy in Weipixiao group and Weifuchun group was 96.55%, 93.10%respectively, the difference being significant (P < 0.05). (3)After treatment, the scores of gastric mucosal atrophy and intestinal metaplasia in the two groups were obviously decreased after treatment (P < 0.05 compared with those before treatment),and the scores of gastric mucosal atypical hyperplasia were decreased obviously in Weipixiao group(P<0.05) but not obviously in Weifuchun group(P>0.05). The inter-group comparison results showed that Weipixiao group had better effect on decreasing gastric mucosal atrophy scores than Weifuchun group(P<0.05). Conclusion Weipixiao has good curative effect for the treatment of CAG patients with spleen-stomach deficiency syndrome through relieving the symptoms and improving the pathological changes of gastric mucosal atrophy and intestinal metaplasia.

Clinical contrast study of Weikangling and Weifuchun for chronic atrophic gastritis and precancerous lesions / 药物评价研究

Objective To explore the clinical effect of Weikangling and Weifuchun treatment of chronic atrophic gastritis and precancerous lesions.Methods 85 cases of CAG precancerous lesions treated in our hospital from Jan.2012 to Dec.2016 were selected as the research object,and were randomly divided into control group (n =41) and study group (n =44).The control group were given Weifuchun,and the study group were given Wei Kangling.The pathological score and clinical efficacy were compared between the two groups before and after treatment.Results After treatment,inflammation,atrophy,intestinal metaplasia scores of the two groups were significantly decreased than before treatment in addition to dysplasia (P ＜ 0.05),and inflammation and intestinal metaplasia in the study group were significantly lower than those in the control group (P ＜ 0.05).The total effective rate of the study group was 90.91％,which was higher than75.61％ of the control group (P ＜ 0.05).Conclusions The effect of Wei Kangling in treating precancerous lesions of CAG is significant,especially for the histological changes of inflammation and intestinal metaplasia.

Clinical contrast study of Weikangling and Weifuchun for chronic atrophic gastritis and precancerous lesions / 药物评价研究

Objective To explore the clinical effect of Weikangling and Weifuchun treatment of chronic atrophic gastritis and precancerous lesions.Methods 85 cases of CAG precancerous lesions treated in our hospital from Jan.2012 to Dec.2016 were selected as the research object,and were randomly divided into control group (n =41) and study group (n =44).The control group were given Weifuchun,and the study group were given Wei Kangling.The pathological score and clinical efficacy were compared between the two groups before and after treatment.Results After treatment,inflammation,atrophy,intestinal metaplasia scores of the two groups were significantly decreased than before treatment in addition to dysplasia (P ＜ 0.05),and inflammation and intestinal metaplasia in the study group were significantly lower than those in the control group (P ＜ 0.05).The total effective rate of the study group was 90.91％,which was higher than75.61％ of the control group (P ＜ 0.05).Conclusions The effect of Wei Kangling in treating precancerous lesions of CAG is significant,especially for the histological changes of inflammation and intestinal metaplasia.

Weifuchun Tablet or Bismuth Combined with Standard Triple Therapy for Helicobacter pylori Eradication: A Clinical Trial / 胃肠病学

Background: Integrative traditional Chinese and western medicine may be a new approach to improve the eradication rate of Helicobacter pylori (Hp).Aims: To compare the efficacy and safety of Weifuchun tablet versus bismuth combined with standard triple regimen as the first-line therapy of Hp infection.Methods: A total of 141 patients with Hp infection and na(i)ve to treatment were randomly assigned into 3 groups receiving a 14-day eradication therapy.In standard triple therapy group, esomeprazole, amoxicillin and clarithromycin were given twice a day;while in Weifuchun group and bismuth group, Weifuchun tablet and bismuth potassium citrate were added, respectively, to the standard triple therapy.Hp eradication was assessed by 13C-urea breath test at least 6 weeks after the end of treatment.Hp isolates were tested for resistance to antibiotics.Results: One hundred and twenty-eight patients completed the study.Hp eradication rates in Weifuchun group, bismuth group and standard triple therapy group were 83.7%, 91.8% and 79.1%, respectively by ITT analysis and 88.4%, 97.8% and 84.6%, respectively by PP analysis.The eradication rate of Weifuchun group was lower than that of bismuth group and higher than that of standard triple therapy group, but the differences were not statistically significant (P>0.05).Only PP eradication rate of bismuth group was significantly higher than that of standard triple therapy group (P0.05).Conclusions: Weifuchun tablet combined with standard triple regimen is safe and effective for use as first-line treatment for Hp infection, however, the eradication rate is relatively low in cases infected with clarithromycin resistant strains.Bismuth combined with standard triple regimen is a good alternative in areas with high clarithromycin resistance and regions where tetracycline is unavailable.

Clinical Observation of Weifuchun Tablet Combined with Rabeprazole Enteric-coated Tablet in the Treat-ment of Chronic Gastritis with Reflux Esophagitis / 中国药房

OBJECTIVE:To observe the efficacy and safety of weifuchun tablet combined with rabeprazole enteric-coated tablet in the treatment of chronic gastritis with reflux esophagitis. METHODS:894 gastritis patients with reflux esophagitis were random-ly divided into control group (407 cases) and observation group (487 cases). Control group was given 10 mg Rabeprazole enter-ic-coated tablet,once a day;observation group was additionally given 1 440 mg Weifuchun tablet,orally,3 times a day. The treat-ment course for both groups was 4-8 weeks. Clinical efficacy,microscopic examination grading,total symptom scores,self-rating anxiety scores(SAS),self-rating depression scores(SDS),quality of life scale score(QOLS),Memorial University of Newfound-land Scale of Happiness score(MUNSH) of reflux esophagitis before and after treatment,and incidence of adverse reactions in 2 groups were observed. RESULTS:The total effective rate in observation group was significantly higher than control group,the dif-ference was statistically significant(P0.05);after treatment,the micro-scopic examination grading cases in 2 groups were significantly superior to before,observation group was superior to control group,total symptom scores,SAS and SDS scores were significantly lower than before,observation group was lower than control group,QOLS and MUNSH scores were significantly higher than before,observation group was higher than control group,the dif-ferences were statistically significant(P0.05). CONCLUSIONS:Weifuchun tablet combined with rabeprazole enteric-coated tablet has better efficacy than only rabeprazole in the treatment of chronic gastritis with reflux esophagitis,it can relieve clinical symptoms of pa-tients,with better safety.

To observe the curative effect of Weifuchun combined Shenqifuzheng pills in the treatment of chronic atroph-ic gastritis / 中国基层医药

Objective To observe the curative effect of Weifuchun combined with Shenqifuzheng pills in the treatment of chronic atrophic gastritis.Methods 85 cases patients were divided into the control group of 42 cases and the treatment group of 43 cases.The control group were treated with omeprazole enteric -coated capsules and colloidal bismmth pectin,while the treatment group were treated with Weifuchun and Shenqifuzheng pills.The course of treatment was two months.The patients were treated by endoscopy and pathological review after the treatment,then the datas were comparedwith that before treatment.Results The total effective rate of the treatment group was 67.44%,which of the control group was 40.48%,the was statistically significant difference between the two groups (χ2 =6.22,P <0.05).The symptom scores of stomach tingling,stomach fullness,facial darkness,anorexia and melena in the two groups had statistically significant differences (t =6.14,P <0.05).Conclusion Weifuchun combined with Shenqi-fuzheng pills have good curative effect in the treatment of chronic atrophic gastritis.It should be popularized in clinic.