Identification and Analysis of Harpagide Metabolites in Rats in vivo / 中国药房

ABSTRACT

OBJECTIVE:To study the metabolites,distribution,metabolic type and the possible activity of harpagide which is the active component from Scrophularia ningpoensis in rats in vivo. METHODS:4 SD rats were divided into blank group (ul-tra-pure water) and administration group (harpagide reference solution),2 in each group,ig,160 mg/kg,twice a day,for 3 d. Urine and feces were collected every 12 h before administration and the first administration;sample blood 8 mL was taken after 0.5,1 h of last administration;heart,liver,spleen,lung,kidney,stomach and small intestine were taken. The blood,urine,fe-ces and other tissue solutions were prepared,HPLC-MS was conducted to detect and identify the harpagide metabolites in rats in vi-vo and presume metabolic pathways,and PharmMapper software was used to predict metabolites activity. RESULTS:12 harpagide metabolites were identified in rats in vivo,the form of prototypes and metabolites were distributed in heart,liver,spleen,lung, kidney,stomach and small intestine. The metabolic type mainly included hydrolysis,dehydration,reduction,methylation,sul-fation,glucuronic acid binding,grade A coumaric acid binding,etc. The 12 compounds may have activities in the treatment of epi-lepsy,amyotrophic lateral sclerosis,diabetes,stroke,etc. CONCLUSIONS:Harpagide may be effective in the form of prototypes and metabolites. The study has provided basis for attributing the origins of metabolite,studying the effective form of S. ningpoensis clarifying its pharmacological mechanism and processing mechanism.