| Topic basis: Originating from Sheng Nong’s herbal classic,Astragali Radix(AR)is the dried root of Astragalus membranaceus(fisch.)bge.var.monghlicus(bge.)or Astragalus membranaceus(fisch.)bge.,which has the functions of invigorating qi,expelling pus,drawing toxin,and promoting diuresis and granulation.Owing to its different planting methods,AR could be divided into wild-simulated AR(WAR)and transplanted AR(TAR).The former has longer growth periods of more than 6 years,higher market prices,and more difficult to harvest than the latter.The planting method of TAR is lateral transplanting after one year of seedling raising.Therefore,these two kinds of AR are whether consistency in pharmacological and clinical application or not,and they should be applied separately? Which planting method of AR can achieve better treatment effects and economic value? The solution of these questions not only perplex its clinical application,but also affect the further development of AR industry.Therefore,it is necessary to compare their pharmacodynamics effects in the practice of traditional Chinese medicine(TCM).TCM formula is the carrier of clinical treatment and effectiveness of TCM.AR has the characteristics of “one medicine and multiple effects”,where it exerts different efficiays in vrious fourmulas in treating different diseases.For example,Fangji huangqi Decoction can treat adriamycin nephropathy by employing its effect of discharging excretion,while Jianzhong Tang(HQJZ)can treat chronic atrophic gastritis(CAG)employing its effect of “invigorating qi for strengthening superficies”.Therefore,it is conducive to better explain the scientific connotation by comparing the efficacy of WAR and TAR in specific compatibility environment against specific disease practice.Nowadays,an increasing number of studies have showed that intestinal flora plays leading roles in the occurrence and development of diseases and also influences the metabolism of its host.In addition,TCM can treat diseases by adjusting the intestinal flora,while the intestinal flora can conversely strengthen the effect of TCM or even detoxify by its metabolism function of oxidation,reduction,hydrolysis and other metabolisms.Therefore,the interaction of TCM,diseases and intestinal flora has become research focus.As an emerging discipline,metabolomics is used to study the changes of metabolites in the organism after the stimulation or disturbance of biological system.It recently has shown great advantages in the overall interpretation of the efficacy and compatibility mechanism of TCM(fomula)by virtue of the characteristics of integrity and dynamics.Similarly,the combination of metabolomics and 16 S r RNA macrogenomic technology systematically studies the interaction between functional intestinal bacteria and organism metabolism,which provides a new way to study the relationship among intestinal flora,metabolism and diseases.Therefore,the present study was aimed to compare the efficacy difference of HQJZ combined different WAR and TAR against CAG,using traditional pharmacodynamic evaluation,metabolomics,fecal metabolism analysis and intestinal flora study.It will provide the scientific basis for the clinical selection of raw materials of AR,and also contribute to the development of AR industry.Objective: To clarify the efficacy difference of HQJZ combined with WAR and TAR in the treatment of CAG rats from the term of the interaction of “traditional Chinese medicine,disease and intestinal flora”.Methods:(1)Eight experimental groups,including control group(C),model group(M),HQJZ group combined with WAR(FF)and TAR(PF),WAR group(FD),TAR group(PF),negative prescription group(Y)and positive drug tipredone group(P),were setted in the pharmacodynamic evaluation.Traditional pharmacodynamic indexes,rat’s appearance state change,weight change trend,gastric p H,pepsin activity and pathological section of stomach tissue,were firstly performed to compare the difference of efficacy of WAR and TAR,as well as the cecum metabolomics.(2)The metabolic disposition of the intestinal flora to HQJZ combined with WAR and TAR were studied by identification of the drug components in vivo.(3)The high throughput sequencing technique of 16 S r RNA was used to study the effect of HQJZ combined with WAR and TAR on the intestinal flora structure of cecum contents in rats with CAG.(4)Two correlation analysis methods,Gramm and Sprarman,were applied to screen out the “metabolite-bacteria” correlation pairs associated with CAG and drug regulations.Results:(1)The traditional pharmacodynamic results showed that the rats in the model group were in poor condition,with the characterizations of significantly reduced weight,increased gastric juice p H value,decreased pepsin activity,and thinner gastric mucosa.After administration,these abnormities were ameliorated with different degrees.The therapeutic effect of HQJZ with WAR was better than that of TAR.The result of metabolomics analysis suggested that 16 different metabolites were closely related to CAG.The effect of HQJZ with WAR on the metabolism profile of cecum contents were better than that of TAR.(2)Through the identification of the drug components in vivo,10 prototypes and 55 metabolites were identified in the FF,4 prototypes and 35 metabolites were identified in the PF,1 prototypes and 8 metabolites were identified in the FD,1 prototypes and 9 metabolites were identified in the PD,7 prototypes and 33 metabolites was identified in Y.The metabolic reactions include oxidized,reduced,methylated,acetylated,desaccharized,demethylated,glucuronized and,etc.Many compounds are metabolized by the combination of phase I and II.(3)The intestinal flora structure of CAG rats changed significantly in the levels of 5 phyla,7 families and 13 genuses.The intestinal flora structure of rats in each group were ameliorated with different degrees after administration.The therapeutic effect of HQJZ with WAR was better than that of TAR.The results of this study indicated that the pathogenesis of chronic atrophic gastritis may be related to the disorder of intestinal flora,while HQJZ might exert therapeutic by regulating the intestinal flora structure.(4)121 pairs of strong correlation pairs(r > 0.5)were screened by GRa MM correlation analysis,and 117 pairs of strong correlation pairs(|r|> 0.5)were screened out by Spearman correlation analysis.There were 12 key strong correlation pairs(|r|> 0.8)between the two methods.The metabolites in these correlation pairs mainly were bile acid metabolites,nucleotide metabolites,amino acid metabolites and fatty acid metabolites.The intestinal flora mainly includes Bacteroides,Parabaceroides,Butricinonas,Desulfovibrio and Eschericia.The overall regulation effect of HQJZ with WAR was better than that of TAR on strong correlation pairs.Conclusion: The present study was aimed to compare the efficiay difference of HQJZ combined different WAR and TAR against CAG,using traditional pharmacodynamic evaluation,metabolomics,fecal metabolism analysis and intestinal flora study.The research results further proved that the efficacy of HQJZ with WAR was better than that of TAR.Moreover,the metabolic disposition of the intestinal flora to HQJZ combined with WAR and TAR were determined by identification of the drug components in vivo.The correlation pair between “metabolite-bacteria” related to the diseases of chronic atrophic gastritis rats was screened by using GRa MM and Sprarman related analysis methods.The results show that the overall regulation effect of HQJZ with WAR was better than that of TAR on strong correlation pairs.This study provides a scientific basis for the clinical selection of raw materials of AR,and also contribute to the development of AR industry. |
PDF Full Text Request