RT Journal Article
SR Electronic
T1 Metabolism of Saikosaponin a in Rats: Diverse Oxidations on the Aglycone Moiety in Liver and Intestine in Addition to Hydrolysis of Glycosidic Bonds
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 622
OP 633
DO 10.1124/dmd.112.048975
VO 41
IS 3
A1 Guoqiang Liu
A1 Yuan Tian
A1 Geng Li
A1 Lei Xu
A1 Rui Song
A1 Zunjian Zhang
YR 2013
UL http://dmd.aspetjournals.org/content/41/3/622.abstract
AB The main objective of the present study was to completely characterize the metabolites of the triterpenoid saikosaponin a (SSa) in rats. To this aim, we compared the metabolites in plasma, bile, urine, and feces samples following oral and i.v. routes of administration using liquid chromatography–diode array detector coupled with hybrid ion trap–time-of-flight mass spectrometry. As a result, besides 2 known metabolites, prosaikogenin f and saikogenin f, 15 new metabolites were detected in all. It was found that SSa is metabolized mainly in phase I manner, i.e., hydration and monooxidation on the aglycone moiety and hydrolysis of the β-glucosidic bond in the liver, and sequential hydrolysis of β-glucosidic and β-fucosidic bonds followed by dehydrogenation, hydroxylation, carboxylation, and combinations of these steps on the aglycone moiety in the intestinal tract. Both the renal and biliary routes were observed for the excretion of SSa and its metabolites. Further, a clear metabolic profile in rats was proposed in detail according to the results from the in vivo animal experiment after different routes of administration. Our results update the preclinical metabolism and disposition data on SSa, which is not only helpful for the future human metabolic study of this compound but also provides basic information for better understanding of the efficacy and safety of prescriptions containing saikosaponins.