Metabonomics Study On The Huangqi Jiangzhong Tang Against Chronic Atrophic Gastritis(CAG) Rats

Huangqi Jiangzhong Tang(HQJZ)was recorded originally in a TCM classic monograph "Synopsis Golden Chamber"(?Jin Gui Yao Lue?).Its effect for chronic atrophic gastritis(CAG)has been proved by clinical and experimental pharmacology.However,the mechanism responsible for its beneficial role is poorly understood,especially for its involved metabolic regulation for CAG.Metabonomics,a new member of omics technologies,considers the human body as a whole system,which is consistent with the TCM concept,and also shows wide application prospects in interpreting the action mechanism and revealing the drug targets of TCM.Therefore,the application might provide an opportunity for the mechanism study of HQJZ against CAG from overall metabolite levels.Objectives: The present study was to address the protective and curative roles of HQJZ in CAG rats and its underlying mechanism based on metabonomics.Methods:1 Chronic atrophic gastritis rat model was successfully constructed by drug stimulation and hunger disorder method.~1H NMR-based metabonomic and pharmacodynamic evaluation were employed to analyze the metabolic features of CAG from prevention and treatment angles.2 The traditional pharmacodynamic evaluation: Body weight,biochemical indexes and histopathological examation were used to evaluate the efficacy of HQJZ against CAG rats.3 ~1H NMR-based metabonomic process: The plasma and urine samples were analyzed by means of ~1H NMR with a goal of obtaining metabolic features spectra.SIMCA-P 13.0 was performed to process multivariate statistical analysis.The classification model was constructed to reveal the differences between different groups.Potential biomarkers were extracted from S-plots and their contribution to the variation(VIP).According to KEGG,HMDB and other databases,all metabolites were attached the metabolic pathways.MetPA analysis was utilized to explore thethe relevant pathways and elucidate the underlying mechanisminvolved into HQJZ against CAG rats.Results:1 The pharmacodynamic results demonstrated the reliability of this model.The HQJZ of clinical dose possessed beneficial activities in treating CAG,and its preventive effect is better than vitacoenzyme,treatment effects consider with teprenone.2 ~1H NMR metabonomics studies of prevention and treatmentrevealed the metabolic regulation of HQJZ against CAG.Thus,5 common plasma potential biomarkers,including succinate,choline,GPC,valine and betaine,which primary involved into Arginine and proline metabolism,Valine,leucine and isoleucine biosynthesis and Glycine,serine and threonine metabolism;7 common urine potential biomarkers,including isoleucine,valine,a-ketoglutarate,fumarate,sarcosine,glycine and hippurate,which primary involved into 3 related metabolic pathways,Valine,leucine and isoleucine biosynthesis,TCA cycle and Glycine,serine and threonine metabolism.Conclusion: The results suggested that the HQJZ could prevent and cure the CAG in rats.The therapeutic effects of HQJZ on CAG were related with its improvement of energy imbalance,excessive oxidative stress,alterations of immune system,as well as inflammation.