Analysis Of Metabolites Of Honey-processed Astragalus In Rats Based On UPLC/Q-TOF-MS

Traditional Chinese medicine for tonifying Qi Radix Astragali and its honey products are widely used in clinical.The raw Astragalus is mainly used to induce diuresis,alleviate edema,promote pus discharge,and tissue regeneration,and the honey-processed Astragalus is used to replace raw Radix Astragali to achieve in reinforcing “Qi”(vital energy).At present,people always focus on the changes of the content of one or several compositions in vitro about raw and honey-processed Astragalus and the pharmacological material basis for its clinical efficacy differences has not been elucidated.The components which are absorbed into the blood have the possibility to become the active ingredients.Drugs in vivo metabolism of the compositions may also play a role in the treatment of diseases.So the study of its body's absorption and metabolism is more conducive to find the efficacy of substances.This study was based on UPLC/Q-TOF-MS combined with multivariate statistical technique to analyze the metabolic profile of urine and serum after oral administration of raw and honey-processed Astragalus water extracts and it provide experimental basis for exploring the material basis of its clinical efficacy differences.In this study,the 39 in vitro components of raw and honey-processed Astragalus,including 16 flavonoids and 15 saponins,were identified by using the kinetex column of Phenomenex.At the same time,the methodological results show that the method is stable and reliable,and can be used for further experimental research.A total of 66 drug metabolites and 9 drug prototypes were analyzed by UPLC/Q-TOF-MS combined with multivariate statistical analysis in rat urine and serum after oral administration of raw and honey-processed Astragalus water extracts.The identified metabolites indicated that the metabolic reactions of Astragalus in rats included deglucosidation,monomethylation,demethylation,hydroxylation,dehydroxylation,sulfation,glucuronidation and hydrogenation.The in vivo migration prototyping components include calycosin-7-O-?-D-glucoside,ononin,calycosin,formononetin,astragaloside IV,astragaloside II,(6aR,11aR)-3-Hydroxy-9,10-dimethoxypterocarpan,7,2'-Dihydroxy-3',4'-dimethoxyisoflavan-7-O-?-D-glucoside and 7,2'-Dihydroxy-3',4'-dimethoxyisoflavan.Finally,PCA and OPLS-DA were used to analyzed the compositions in rat serum and urine after oral administration water extracts,17 and 20 differential metabolites were found in the drug-containing urine and serum respectively.In addition,this study also determine the contents of the main components in the drug-containing serum by UPLC/Q-TOF-MS.The results showed that the content of calycosin-7-O-?-D-glucoside and ononin in honey-processed group were significantly higher than those of the raw group and thus indicating that semi-quantitative results are reliable.The above results show that there have significant differences in the absorption and metabolism of the rats after oral administration raw and honey-processed Astragalus water extracts.Among these differential metabolites,calycosin-7-O-?-D-glucoside,calycosin,ononin and formononetin are the drug prototypes,suggesting that they might be related to the difference of clinical efficacy before and after honey-processing.At the same time,the metabolic profile in rat after oral administration raw and honey-processed Astragalus waters extracts was found to provide the basic conditions for the differential efficacy of honey-processed Astragalus.