Banxia xiexin decoction prevents the development of gastric cancer

BACKGROUND In China banxia xiexin decoction(BXD)has been used in treating gastric cancer(GC)for thousands of years and BXD has a good role in reversing GC histopathology,but its chemical composition and action mechanism are still unknown.AIM To investigate the mechanism of action of BXD against GC based on transcriptomics,network pharmacology,in vivo and in vitro experiments.METHODS The transplanted tumor model was prepared,and the nude mouse were pathologically examined after administration,and hematoxylin-eosin staining was performed.The active ingredients of BXD were quality controlled and identified using ultra-performance liquid chromatography tandem quadrupole electrostatic field orbitrap mass spectrometry(UPLC-Q-Orbitrap MS/MS),and traditional Chinese medicines systems pharmacology platform,drug bank and the Swiss target prediction platform to predict the relevant targets,the differentially expressed genes(DEGs)of GC were screened by RNA-seq sequencing,and the overlapping targets were analyzed to obtain the key targets and pathways.Cell Counting Kit-8,apoptosis assay,cell migration and Realtime fluorescence quantitative polymerase chain reaction were used for in vitro experiments.RESULTS All dosing groups inhibited the growth of transplanted tumors in laboratory-bred strain nude,with the capecitabine group and the BXD medium-dose group being the best.A total of 29 compounds and 859 potential targets in BXD were identified by UPLC-Q-Orbitrap MS/MS and network pharmacology,RNA-seq sequencing found 4767 GC DEGs,which were combined with network pharmacology and analyzed 246 potential therapeutic targets were obtained and pathway results showed that BXD may against GC through the Phosphoinositide 3-kinase(PI3K)/protein kinase B(AKt)signaling pathway.In vitro cellular experiments confirmed that BXDcontaining serum and LY294002 could inhibit the proliferation of GC cells,promote apoptosis,and inhibit the migration of GC cells by decreasing the expression of EGFR,PIK3CA,IL6,BCL2 and AKT1 in the PI3K-Akt pathway in MGC-803 expression.CONCLUSION BXD has the effect of inhibiting tumor growth rate and delaying the development of GC.Its mechanism of action may be related to the regulation of PI3K-Akt signaling pathway.

BanXiaXieXin decoction treating gastritis mice with drug-resistant Helicobacter pylori and its mechanism

BACKGROUND Helicobacter pylori(H.pylori)is the main pathogen that causes a variety of upper digestive diseases.The drug resistance rate of H.pylori is increasingly higher,and the eradication rate is increasingly lower.The antimicrobial resistance of H.pylori is an urgent global problem.It has been confirmed that Banxia Xiexin decoction(BXXXT)demonstrates the effects of treating gastrointestinal diseases,inhibiting H.pylori and protecting gastric mucosa.The purpose of the present study is to further explore the therapeutic effects of BXXXT on drug-resistant H.pylori.AIM To confirm that BXXXT demonstrates therapeutical effects in vivo and in vitro on gastritis mice with drug-resistant H.pylori and explain its mechanism to provide an experimental basis for promoting the application of BXXXT.METHODS The aqueous extract of BXXXT was gained by water decocting method.The inhibitory effect of the aqueous extract on H.pylori was detected by dilution in vitro;drug-resistant H.pylori cells were used to build an acute gastritis model in vivo.Thereafter,the model mice were treated with the aqueous extract of BXXXT.The amount of H.pylori colonization,the repair of gastric mucosal damage,changes of inflammatory factors,apoptosis,etc.,were assessed.In terms of mechanism exploration,the main medicinal compositions of BXXXT aqueous extract and the synergistic bacteriostatic effects they had demonstrated were analyzed using mass spectrometry;the immune function of peripheral blood cells such as CD3+T and CD4+T of mice with gastritis before and after treatment with BXXXT aqueous extract was detected using a flow cytometry;the H.pylori transcriptome and proteome after treatment with BXXXT aqueous extract were detected.Differently expressed genes were screened and verification was performed thereon with knockout expression.RESULTS The minimum inhibitory concentration of BXXXT aqueous extract against H.pylori was 256-512μg/mL.A dose of 28 mg/kg BXXXT aqueous extract treatment produced better therapeutical effects than the standard triple therapy did;the BXXXT aqueous extract have at least 11 ingredients inhibiting H.pylori,including berberine,quercetin,baicalin,luteolin,gallic acid,rosmarinic acid,aloe emodin,etc.,of which berberine,aloe emodin,luteolin and gallic acid have a synergistic effect;BXXXT aqueous extract was found to stimulate the expressions of CD3+T and CD4+T and increase the number of CD4+T/CD8+T in gastritis mice;the detection of transcriptome and proteome,quantitative polymerase chain reaction,Western blotting and knockout verification revealed that the main targets of BXXXT aqueous extract are CFAs related to urea enzymes,and CagA,VacA,etc.CONCLUSION BXXXT aqueous extract could demonstrate good therapeutic effects on drug-resistance H.pylori in vitro and in vivo and its mechanism comes down to the synergistic or additional antibacterial effects of berberine,emodin and luteolin,the main components of the extract;the extract could activate the immune function and enhance bactericidal effects;BXXXT aqueous extract,with main targets of BXXXT aqueous extract related to urease,virulence factors,etc.,could reduce the urease and virulence of H.pylori,weaken its colonization,and reduce its inflammatory damage to the gastric mucosa.

Systematic Review and Meta-analysis of Efficacy of Banxia Xiexin Decoction for Treatment of Bile Reflux Gastritis

[Objectives]The purpose was to study the clinical efficacy and safety of Banxia Xiexin decoction in treating bile reflux gastritis(BRG).[Methods]Randomized controlled trial was adopted to conduct scientific and standardized assessment on the risk of bias in the included articles.With overall effect and epigastric pain relief as indices,meta-analysis was performed,and sensitivity and safety analysis was conducted on the included literature.[Results]A total of 13 articles were included,involving a total of 1478 patients.The results of meta-analysis show that the efficacy of Banxia Xiexin decoction alone and Banxia Xiexin decoction-Western medicine combination is better than that of Western medicine alone.[Conclusions]Banxia Xiexin decoction is safe and effective in treating bile reflux gastritis.However,as the 13 articles included are all low in quality and there is a certain degree of publication bias,the objectivity of the results is affected to some extent.

Banxia Xiexin Decoction for patients with peptic ulcer or chronic gastritis infected with Helicobacter pylori

Objective:To compare the effectiveness and safety of Banxia Xiexin Decoction (BXD) as alternative therapy versus standard triple therapy or quadruple therapy for patients with peptic ulcer or chronic gastritis infected with Helicobacter pylori (H.pylori).Methods:Databases including China National Knowledge Infrastructure,Chongqing VIP,Wanfang Database,PubMed,the Cochrane Library and clinicaltrials.gov were searched in December 2018 for relevant randomized controlled trials (RCTs).Two authors independently screened and selected studies,extracted data and checked data extraction.Methodological quality was evaluated using the Cochrane Risk of Bias tool.Meta-analysis was performed by using RevMan 5.3.5 software.Results:Fourteen RCTs were included in our analysis involving 1300 patients.Thirteen RCTs compared the effects of BXD alone versus standard therapy,11 involving triple therapy and 2 in quadruple therapy.The cure rate for both diseases were higher in the BXD alone group than in the standard therapy group (RR and 95% Cl:1.85 [1.07,3.17] and 1.48 [1.24,1.75],respectively).And also,the same result with effectiveness rate (RR and 95% CI:1.18 [1.08,1.29] and 1.14 [1.08,1.20],respectively).However,there was no significant difference in the clearance of H.pylori one month after treatment,neither compared with quadruple therapy nor triple therapy (RR and 95% CI:1.10 [1.00,1.22] and 1.04 [0.97,1.12],respectively).Adverse events appeared in 3 participants in the BXD group and 26 participants in the conventional therapy group.The quality of the trials included in this review was not very good.Conclusion:BXD has a superior effect to standard conventional therapy in improving clinical symptoms and repair of the mucosal lesion,and a similar effect to standard conventional therapy in clearing H.pylori.We still need good quality trials,especially placebo-controlled trials,in the future to confirm this result.

Therapeutic targets and signal transduction mechanisms of medicinal plant formula Gancao Xiexin decoction against ulcerative colitis:A network pharmacological study

Background:Ulcerative colitis(UC)is a chronic disease that often presents with abdominal pain,diarrhea,hematochezia,and significant morbidity.Gancao Xiexin decoction(GXD),a traditional Chinese medicine,has been applied for the clinical treatment of UC,while its action mechanisms are unclear.Methods:The active ingredients and their targets of GXD,and UC-related targets,were derived from public databases.Protein-protein interaction,Gene Ontology(GO),and the Kyoto Encyclopedia of Genes and Genomes(KEGG)were used to analyze the important active compounds,key targets,and signaling pathways.Then,molecular docking and animal experiments were performed to verify the findings.A total of 213 active compounds and 89 common targets of GXD for UC were obtained.Results:The hub gene network showed ALB,AKT1,IL6,TNF,VEGFA,TP53,CXCL8,MAPK1,PTGS2,and IL1βmay be potential targets of GXD against UC.GO and KEGG pathway enrichment analyses suggested that the action of GXD against UC was mainly related to response to oxygen levels,lipopolysaccharide,and molecule of bacterial origin,etc.,and achieved by advanced glycation endproducts/receptors for advanced glycation endproducts signaling pathway in diabetic complications,hypoxia-inducible factor(HIF)-1 signaling pathway,interleukin-17/HIF-1 signaling pathway,TNF signaling pathway,etc.Molecular docking results showed that the GXD had good potency of action with the hub target.In vivo experiments showed that GXD significantly alleviated the symptoms of UC and down-regulated the expression of inflammatory factors,nuclear factor-κB and signal transducer and activator of transcription 3.Conclusions:The anti-UC action of GXD is mainly attributed to its anti-oxidative stress,antiinflammatory,and immunomodulatory functions.

Research progress and clinical experience of Banxia Xiexin Decoction in the treatment of insomnia

Insomnia is a common clinical disease.At present,with the increase of work and life pressure,the incidence of insomnia is increasing year by year,which seriously affects people's physical and mental health and quality of life.Although stable drugs are effective in the treatment of insomnia,they have long-term side effects.Traditional Chinese medicine has unique advantages in the treatment of insomnia.Among them,Banxia Xiexin Decoction is based on the theory of"stomach disorder,sleep restlessness".Curative effect.By searching relevant literature,this article discusses the research progress of Banxia Xiexin Decoction in the treatment of insomnia from the theory,prescription and clinical research of Banxia Xiexin Decoction,and describes the clinical experience of using Banxia Xiexin Decoction.In order to provide some reference for the clinic.

Study on the mechanism of Shengjiang Xiexin Decoction in the treatment of chemotherapy-induced diarrhea based on network pharmacology and molecular docking

Objective:To explore the key targets and mechanism of Shengjiang Xiexin Decoction in the treatment of chemotherapy-induced diarrhea based on network pharmacological methods.Methods:The effective components and corresponding target proteins of Shengjiang Xiexin Decoction were screened by TCMSP,and the target of chemotherapy-induced diarrhea were screened by the GeneCards.R software was used to obtain the common targets of drugs and diseases,and the“component-target-disease”network diagram was constructed by Cytoscape3.8.0 software.The string datebase was used to draw the protein interaction(PPI)network,and the Bioconductor software was used to perform GO function and KEGG pathway enrichment analysis on effective targets.Result:The result showed that 216 components were screened and 276 effective targets were screened.There were 1764 chemotherapy-induced diarrhea targets.The 173 common targets were obtained through venn diagram.The GO function analysis found 2427 items of biological process,168 items of molecular function and 79 items of cellular component.The KEGG pathway analysis found 169 items.Conclusion:The PPI network found that STAT3、AKT1、MAPK3、JUN、MAPK1、RELA、IL6、etc.may be the key targets for Shengjiang Xiexin Decoction in treatment of chemotherapy-induced diarrhea.GO biological processes include DNA-binding transcription factor activity,cytokine receptor binding,cytokine activity,response to lipopolysaccharide,cellular response to chemical stress and so on.The KEGG pathways involved mainly include Toll-like receptor signaling pathway,TNF signaling pathway,inlfuenza A signaling pathway、hepatitise B signaling pathway and other pathways,that Play the role of anti-inflammatory and repair barrier.

Network pharmacology analysis of the mechanisms of Banxia Xiexin Decoction against Ulcerative Colitis

Banxia Xiexin Decoction(BXXXD),a traditional herbal formula,has been used to treat ulcerative colitis(UC)clinically.In this study,chemical compounds and putative targets of BXXXD and UC related therapeutic targets were screened from multiple databases.The protein-protein interaction(PPI)was conducted using String database,and 31 candidate targets were screened from CytoNCA database.The Database for Annotation,Visualization and Integrated Discovery(DAVID)and Metascape database were used for Kyoto Encyclopedia of Genes and Genomes(KEGG)channel and Gene Ontology(GO)enrichment analysis respectively,and the enrichment analysis results were visualized by OmicShare platform.Meanwhile,the interaction network among Chinese herbs,active compounds,candidate targets and pathways was built by Cytoscape 3.7.2 software,and the potential compounds of BXXXD in the treatment of UC were screened.Finally,molecular docking technology was used to verify the putative key compounds.Combined with literature research,5 key compounds for the treatment of UC were identified,which are mainly involved in TNF signaling pathway,cancer signaling pathway,inflammatory bowel disease(IBD),Toll-like receptor signaling pathway,and NF-κB signaling pathway.This study provides a scientific basis for BXXXD as an effective alternative therapeutic agent for UC from a new perspective,and also provides a feasible method for basic chemical research and pharmacological research of BXXXD.

A meta-analysis of Banxia Xiexin decoction versus omeprazole in the treatment of gastroesophageal reflux disease

Objective:To investigate the clinical efficacy and safety of Banxia Xiexin decoction and omeprazole in the treatment of gastroesophageal reflux disease(GERD).Methods:EMbase,Cochrane,PubMed,CNKI,Wan Fang and VIP database were searched from inception to November 2018 according to the search strategy.Eligible randomized controlled clinical trials related to the efficacy of omeprazole compared with Banxia Xiexin decoction in the treatment of GERD were included according to the inclusion and exclusion criteria.Total effective rate,pathological improvement rate,total symptom score,acid reflux symptoms,heartburn symptoms,improvement of post-sternal pain symptoms,and incidence of adverse reactions were evaluated.Data analysis was performed with RevMan5.3 software provided by Cochrane Collaboration.Results:A total of 15 studies were enrolled,including 1,532 patients.Meta-analysis results showed that the total effective rate of Banxia Xiexinfang was higher than that of omeprazole in the treatment of GERD(odds ratio(OR)=3.99,95%confidence intervals(CI)(2.58,6.15),P<0.00001).Pathological improvement under endoscopy was not obvious(OR=1.98,95%CI(0.94,4.19),P=0.07)between the two groups.The total symptom score improved significantly,indicating that Banxia Xiexin decoction has an objective advantage over omeprazole in the treatment of GERD(standardised mean difference(SMD)=?2.56,95%CI(?3.86,?1.26),P=0.0001),The incidence of adverse reactions in patients treated with Banxia Xiexin decoction is lower than omeprazole group(OR=0.09,95%CI(0.02,0.39),P=0.001].In addition,total effective rate of Banxia Xiexin decoction combined with omeprazole was higher than omeprazole alone(OR=6.31,95%CI(2.86,13.92),P<0.00001).Conclusion:Banxia Xiexin decoction is superior to omeprazole in total effective rate,total symptom score and adverse reaction rate in the treatment of GERD.The clinical efficacy of Banxia Xiexin decoction combined with omeprazole is better than that of omeprazole alone.However,due to the low quality of the included literatures,large-scale and high-quality RCTs are still needed for further confirmation.

Discussion on the Theoretical Basis of Banxia Xiexin Decoction in the Treatment of Insulin Resistance Obesity

Through reading Chinese ancient book Huangdi Nejing,and summarizing and analyzing related literature,the basic pathogenesis of obesity have been found to be the stomach preponderance and spleen weakness,and the imbalance of ascending and descending.Banxia Xiexin Decoction not only has the functions of relieving heat to inhibit stomach intake,supplementing deficiency to assist spleen transport,regulate the ascending and descending,but also has the effects of improving insulin resistance and regulating glucolipid metabolism.Therefore,it is suggested that Banxia Xiexin Decoction can be used in the treatment of insulin resistant obesity,which provides ideas and methods for its treatment.

Efficacy and safety of Banxia Xiexin Decoction in the treatment of gastric ulcer:a systematic review and meta-analysis of twenty-seven randomized controlled trials

Background:Banxia XieXin Decoction(BXD)is a traditional Chinese medicine decoction commonly used in the Chinese clinical treatment of gastric ulcer(GU).Although some people believe that it may have some advantages in this regard,There is no reliable evidence-based study demonstrating its effectiveness.This study aims to systematically evaluate the healing effect and security of BXD in the treatment of GU.Methods:PubMed,Cochrane Library,EMBASE,ScienceNet,China National Knowledge Infrastructure(CNKI),Wanfang database,Weipu database,and China biomedical literature service(CBM)database were systematically searched to obtain all randomized controlled trials(RCTs)evaluating the treatment GU of BXD published as of April 2022.Two researchers independently screened and extracted all research data,finally evaluated the bias risk of inclusion in the study using revman 5.4.Results:This meta-analysis included 27 randomized controlled trials and 1411 patients.The clinical effective rate,recurrence rate,HP eradication rate,adverse reaction rate,and visual analog score(VAS)of BXD combined treatment and standard treatment alone were compared.The results of the meta-analysis showed that BXD combined treatment improve the symptoms related to the gastric ulcers and reduce drug-related adverse reactions.Due to the low quality of the research included in this analysis,in-depth high-quality research is crucial for verifying these results.

Explanation of Banxia Xiexin decoction based on “Xinkai Kujiang”

Banxia Xiexin decoction(BXD)is a representative formula of Zhang Zhongjing(Eastern Han Dynasty)for the treatment of pi syndrome,which is a combination of cold and heat,and its application in the treatment of digestive system diseases is remarkable.In this paper,we discuss how Chinese medicine recognizes“spleen”and“Pi syndrome”to explain and explore the basis of BXD prescription and analyze both clinical examples and drug toxicity to provide more basis for the clinical application of BXD.

UPLC-Q-TOF/MS-Based Serum Metabolomics Reveals Potential Anti-tumor Mechanism of Banxia Xiexin Decoction in Colorectal Cancer Mice

Objective To clarify the potential mechanism of Banxia Xiexin Decoction(BXD)on colorectal cancer(CRC)from the perspective of metabolomics.Methods Forty male C57BL/6 mice were randomly divided into normal control(NC),azoxymethane/dextran sulfate sodium(AOM/DSS)model,low-dose BXD(L-BXD),high-dose BXD(H-BXD)and mesalamine(MS)groups according to a random number table,8 mice in each group.Colorectal cancer model was induced by AOM/DSS.BXD was administered daily at doses of 3.915(L-BXD)and 15.66 g/kg(H-BXD)by gavage for consecutive 21 days,and 100 mg/kg MS was used as positive control.Following the entire modeling cycle,colon length of mice was measured and quantity of colorectal tumors were counted.The spleen and thymus index were determined by calculating the spleen/thymus weight to body weight.Inflammatory cytokine and changes of serum metabolites were analyzed by enzyme-linked immunosorbent assay kits and ultra performance liquid chromatography-quadrupole/time-of-flight mass spectrometry(UPLC-Q/TOF-MS),respectively.Results Notably,BXD supplementation protected against weight loss,mitigated tumor formation,and diminished histologic damage in mice treated with AOM/DSS(P<0.05 or P<0.01).Moreover,BXD suppressed expression of serum inflammatory enzymes,and improved the spleen and thymus index(P<0.05).Compared with the normal group,102 kinds of differential metabolites were screened in the AOM/DSS group,including 48 potential biomarkers,involving 18 main metabolic pathways.Totally 18 potential biomarkers related to CRC were identified,and the anti-CRC mechanism of BXD was closely related to D-glutamine and D-glutamate metabolism,phenylalanine,tyrosine and tryptophan biosynthesis,arginine biosynthesis,nitrogen metabolism and so on.Conclusion BXD exerts partial protective effects on AOM/DSS-induced CRC by reducing inflammation,protecting organism immunity ability,and regulating amino acid metabolism.

Sanhuang Xiexin Decoction Ameliorates TNBC by Modulating JAK2-STAT3 and Lipid Metabolism

Objective:To investigate the therapeutic effect of Sanhuang Xiexin Decoction(SXD)on triplenegative breast cancer(TNBC)in mice and its underlying mechanism.Methods:The high-performance liquid chromatography(HHLC)was used to quantitate and qualify SXD.A total of 15 female BALB/c mice were inoculated subcutaneously on the right hypogastrium with 3×10^(5) of 4T1-Luc cells to establish TNBC mouse model.All mice were divided randomly into 3 groups,including phosphate buffered solution(PBS),SXD and doxorubicin(DOX)groups(positive drug).Additionally,tumor growth,pathological changes,serum lipid profiles,expression of Janus kinase 2(JAK2)-signal transducer and activator of transcription 3(STAT3)signaling pathway and its key targets including inflammatory factors,cell cycle and epithelial-mesenchymal transition(EMT)markers were investigated.Besides,the biosafety of SXD was also evaluated in mice.Results:Rhein,coptisine,berberine hydrochloride and baicalin were all found in SXD,and the concentrations of these 4 components were 0.57,2.61,2.93,and 46.04 mg/g3respectively.The mouse experiment showed that SXD could notably suppress the development of tumors and reduce the density of tumor cells(P<0.01).The serum lipid analysis and Oil-Red-O staining both showed the differences,SXD group exhibited higher serum adiponectin and HDL-C levels with lower TC and LDL-C levels compared to the PBS and DOX groups(P<0.05 or P<0.01),respectively.SXD also decreased the levels of phospho-JAK2(p-JAK2),phospho-STAT3(p-STAT3)expressions and its downstream factors,including mostly inflammatory cytokine,EMT markers,S phase of tumor cells and vascular endothelial growth factor(VEGF)expression(P<.05 or P<0.01),respectively.The biosafety assessment of SXD revealed low levels of toxicity in mice.Conclusion:SXD could inhibit TNBC by suppressing JAK2-STAT3 phosphorylation which may be associated with modulation of lipid metabolism.

Banxia Xiexin Decoction Alleviated Cerebral Glucose Metabolism Disorder by Regulating Intestinal Microbiota in APP/PS1 Mice

Objective To identify whether Banxia Xiexin Decoction(BXD)alleviates cerebral glucose metabolism disorder by intestinal microbiota regulation in APP/PS1 mice.Methods Forty-five 3-month-old male APP/PS1 mice were divided into 3 groups using a random number table(n=15 per group),including a model group(MG),a liraglutide group(LG)and a BXD group(BG).Fifteen 3-month-old male C57BL/6J wild-type mice were used as the control group(CG).Mice in the BG were administered BXD granules by gavage at a dose of 6 g/(kg·d)for 3 months,while mice in the LG were injected intraperitoneally once daily with Liraglutide Injection(25 nmol/kg)for 3 months.Firstly,liquid chromatography with tandem-mass spectrometry was used to analyze the active components of BXD granules and the medicated serum of BXD.Then,the cognitive deficits,Aβpathological change and synaptic plasticity markers,including synaptophysin(SYP)and postsynaptic density protein 95(PSD95),were measured in APP/PS1 mice.Brain glucose uptake was detected by micropositron emission tomography.Intestinal microbial constituents were detected by 16S rRNA sequencing.The levels of intestinal glucagon-like peptide 1(GLP-1)and cerebral GLP-1 receptor(GLP-1R),as well as the phosphoinositide-3-kinase/protein kinase B/glycogen synthase kinase-3β(PI3K/Akt/GSK3β)insulin signaling pathway were determined by immunohistochemical(IHC)staining and Western blot analysis,respectively.Results BXD ameliorated cognitive deficits and Aβpathological features(P<0.01).The expressions of SYP and PSD95 in the BG were higher than those in the MG(P<0.01).Brain glucose uptake in the BG was higher than that in the MG(P<0.01).The intestinal microbial composition in the BG was partially reversed.The levels of intestinal GLP-1 in the BG were higher than those in the MG(P<0.01).Compared with the MG,the expression levels of hippocampal GLP-1R,Akt,PI3K and p-PI3K in the BG were significantly increased(P<0.01),while the levels of GSK3βwere reduced(P<0.01).Conclusion BXD exhibited protective effects against Alzheimer’s disease by regulating the gut microbiota/GLP-1/GLP-1R,enhancing PI3K/Akt/GSK3βinsulin signaling pathway,and improving brain glucose metabolism.

Efficacy of Banxia Xiexin decoction in a rat model of chronic atrophic gastritis

OBJECTIVE:To investigate the effectiveness of Banxia Xiexin decoction(BXD)in a rat model of chronic atrophic gastritis(CAG).METHODS:Sixty 6-week-old healthy Wistar rats(30 males,30 females)were used in the present study.A rat model of CAG was successfully established using the combined active immunization/ethanol/sodium deoxycholate method.BXD was prepared from a mixture of seven Chinese herbs,and was intragastrically administered to CAG rats at three different doses(6,12,and 24 g·kg^-1·d^-1).Af-ter 24 weeks,the rats were euthanized,and gastric tissue specimens were collected.Gastric mucosal specimens were stained with hematoxylin and eosin for histological examination to evaluate the degree of inflammation and morphological changes.Immunohistochemical staining was performed to examine the mucosal expression of proliferating cell nuclear antigen.Serum gastrin levels were measured using radioimmunoassay.The expression of Notch signaling-associated genes was examined by quantitative polymerase chain reaction and Western blot assay.RESULTS:BXD at all three doses significantly reversed the adverse effects generated by CAG in rats.Compared with control rats,the CAG rats who were administered BXD had an accelerated growth rate,reduced inflammatory cell infiltration,improved gastric mucosal morphology,augmented thickness of the gastric mucosa,increased number of gastric glands,enhanced mucosal expression of proliferating cell nuclear antigen,and elevated serum gastrin levels.

Effects of Banxia Xiexin Decoction (半夏泻心汤) on Cisplatin-Induced Apoptosis of Human A549 Lung Cancer Cells

Objective： To examinie the synergistic effects of Banxia Xiexin Decoction （半夏泻心汤, Known as Banhasasim-tang in Korean） extract （BXDE） on cisplatin-induced cytotoxicity in the A549 human lung cancer ceil lines. Methods： A549 cells were treated with varying concentrations （50-200μg/mL） of cisplatin and BXDE alone or in combination for 96 h. We used 1-（4,5-dimethylthiazol-2-yl）-3,5-diphenylformazan assay and flow cytometry to analyze cell viability and apoptosis, respectively. Results： The exposure of cells to cispiatin and BXDE alone or in combination decreased ceil viability dose- and time-dependently （P〈0.05）, which was found to be mediated by the apoptotic pathway as confirmed by the increase in the annexin V^＋/propidium iodide stained cell population and a ladder pattern of discontinuous DNA fragments. Furthermore, the apoptosis was inhibited by the pan-caspase inhibitor, benzyloxycarbonyI-Val-Ala-Asp （OMe） fluoromethylketone （z-VAD-FMK）. Conclusions： BXDE significantly potentiated apoptotic effects of cisplatin in A549 cells. Moreover, apoptosis induced by BXDE might be the pivotal mechanism mediating its chemopreventative action against cancer.

Effect of a modified Banxia Xiexin decoction plus chemotherapy on stage Ⅲ colon cancer

OBJECTIVE: To investigate the effect of a modified Banxia Xiexin decoction(MBXD) plus chemotherapy on postoperative adverse reaction in patients with stage Ⅲ colon cancer in patients whose symptoms were identified as cold-heat complicated pattern in terms of the theory of Traditional Chinese Medicine(TCM).METHODS: A prospective non-randomized control study of patients with stage Ⅲ colon cancer in Beijing Shijitan Hospital and Guang'anmen Hospital between January 2012 and December 2013. A total of 80 patients were divided into experimental group(MBXD + chemotherapy) and control group(chemotherapy). The adverse reactions, life quality and disease-free survival(DFS) were compared between the two groups.RESULTS: The cold-heat complex pattern was released in 94.3% of patients in experimental group whereas 62.2% in control group(P < 0.05). Life quality was improved in 24 vs 14 cases, stabilized in 9 vs14 cases whereas decreased in 2 vs 15 cases in experimental group and control group, respectively(P < 0.05). The average DFS was 22.371 months in experimental group, while 13.932 months in control group(P < 0.05).CONCLUSION: MBXD combined with chemotherapy may significantly relieve clinical symptoms, reduce chemotherapy associated adverse effects, improve life quality, and prolong DFS of patients with stage Ⅲ colon cancer(cold-heat complicated pattern).

Effect of Banxia Xiexin decoction on Helicobacter pylori-related peptic ulcers and its possible mechanism via the TGF-β/Smad signaling pathway

OBJECTIVE: To investigate the effect of Banxia Xiexin decoction(BXD) on Helicobacter pylori(Hp)-related peptic ulcers(PUs) and the possible mecha-nism underlying BXD actions via the transforming growth factor-β/small mothers against decapentaplegic(TGF-β/Smad) signaling pathway.METHODS: PU patients with cold-heat complex syndrome were randomly assigned to groups that received Chinese or Western medicines with 20 patients in each group. Serum was collected after 7 d of treatment. The healthy group included 20 individuals. Gastric mucosal epithelial cell line GES-1 was cultured in vitro and randomly divided into the following seven groups: control, model, healthy,Western Medicine, prior treatment, low dosage,and high dosage. After 72 h of treatment with the corresponding serum, the m RNA and protein expression levels of TGF-β1, Smad3, and Smad7 were measured by reverse transcription quantitative polymerase chain reaction and western blotting, respectively.RESULTS: The m RNA expression levels of TGF-β1 and Smad3 in GES-1 cells were increased after Hp introduction, and these increased levels were reduced by the BXD-containing serum. The protein levels of p-Smad3, but not TGF-β1 or Smad3, were significantly increased in Hp-treated GES-1 cells,and treatment with the BXD-containing serum markedly decreased the protein levels. Smad7 expression was significantly enhanced following treatment with the BXD-containing serum at transcriptional and protein levels in a dose-dependent manner.CONCLUSION: BXD regulates the TGF-β/Smad signaling pathway by inhibiting the expression of TGF-β1 and Smad3, and increasing the expression of Smad7.

Banxia Xiexin Decoction(半夏泻心汤)Treats Diabetic Gastroparesis through PLC-IP3-Ca^2+/NO-cGMP-PKG Signal Pathway

Objective To test the effect of Banxia Xiexin Decoction(半夏泻心汤,BXD)on the contraction and relaxation of gastric smooth muscle(SM)in diabetic gastroparesis(DGP)model rats,and to explore the mechanism of BXD in the prevention and treatment of DGP through experiments of signal pathway both in vivo and in vitro.Methods Sixty Sprague-Dawley rats were divided into 6 groups according to a random number table:control group,model group,high-,medium-and low-dose BXD groups(9.2,4.6 and 1.8 g/(kg·d),respectively),and domperidone group(10 mg/(kg·d)),10 rats per group.DGP model was established initially by a single intraperitoneal injection of streptozotocin(STZ),and was confirmed by recording gastric emptying,intestinal transport velocity and gastric myoelectric activity of rats after 2 months.Each group was treated with a corresponding drug for 4 weeks.The mRNA and protein expressions of phospholipase C(PLC),inositol triphosphate(IP3),neuronal nitric oxide synthase(nNOS),and cyclic guanosine monophosphate(cGMP)dependent protein kinase G(PKG)were detected by reverse transcription-polymerase chain reaction and Western blot,respectively,while nitric oxide(NO)and cGMP expressions were detected by enzyme-linked immunosorbent assay.Gastric tissues were obtained from rats for primary cell culture preparation.Gastric SM cells were treated with 0.8µmol/L of STZ or STZ plus 1,000,500 and 200µg/mL of BXD or STZ plus 2.5µmol/mL of domperidone for 24,48,72 or 96 h,respectively.The length of gastric SM cells and intracellular Ca^2+concentration([Ca^2+]i)before and after BXD treatment was measured.Results Compared with the model group,high-and medium-dose BXD and domperidone significantly increased the expressions of PLC,IP3,NO,nNOS,cGMP and PKG in rat’s gastric tissue(P<0.01).Gastric SM cells treated with BXD showed a time-and dose-dependent increase in cell viability(P<0.01).The treatment with high-and medium-dose BXD and domperidone inhibited the increase in gastric SM cells length and increased[Ca^2+]i compared with the model cells(P<0.01).Conclusions Treatment with high-and medium-dose BXD significantly attenuated STZ-induced experimental DGP in rats.The therapeutic effect of BXD on DGP rats might be associated with the PLC-IP3-Ca^2+/NO-cGMP-PKG signal pathway.