Structural Analysis of Metabolites of Asiatic Acid and Its Analogue Madecassic Acid in Zebrafish Using LC/IT-MSn

Molecules

Binbin Xia²  Lu Bai²  Xiaorong Li²  Jie Xiong²  Pinxiang Xu²  Ming Xue¹ 

[1] Beijing Laboratory for Biomedical Detection Technology and Instrument, Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China;

关键词: zebrafish;    metabolism;    asiatic acid;    madecassic acid;    LC/IT-MSⁿ;   

DOI  :  10.3390/molecules20023001

来源: mdpi

【 摘 要 】

Although zebrafish has become a significant animal model for drug discovery and screening, drug metabolism in zebrafish remains largely unknown. Asiatic acid (AA) and madecassic acid (MA), two natural pentacyclic triterpenoids mainly obtained from Centella asiatica (L.) Urban, have been found to possess many pharmacological effects. This study is to probe the metabolic capability of zebrafish via investigation of the drug metabolism of AA and MA in zebrafish, using a sensitive LC/IT-MSⁿ method. In addition, the main fragmentation pathways of AA and MA were reported for the first time. Nineteen metabolites of AA and MA were firstly identified after zebrafish was exposed to the drug, which all were the phase I metabolites and mainly formed from hydroxylation, dehydrogenation, hydroxylation and dehydrogenation, dihydroxylation and dehydrogenation, and dehydroxylation reaction. The results indicated that zebrafish possessed strong metabolic capacity, and the metabolites of AA and MA were formed via similar metabolic pathways and well matched with the known metabolic rules in vivo and in vitro, which supports the widely use of this system in drug metabolism research. This investigation would also contribute to the novel information on the structural elucidation, in vivo metabolites and metabolic mechanism of pentacyclic triterpenoids.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.