Metabolism of Tanshinone IIA, Cryptotanshinone and Tanshinone I from Radix Salvia Miltiorrhiza in Zebrafish

Abstract

The study aimed to investigate the potential of zebrafish in imitating mammal phase I metabolism of natural compounds. Three diterpenoid quinones from Radix Salvia miltiorrhiza, namely tanshinone IIA (TIIA), cryptotanshinone (Cry) and tanshinone I (TI) were selected as model compounds, and their metabolites mediated by zebrafish were characterized using a high-performance liquid chromatography coupled ion-trap mass spectrometry (HPLC/IT-MSn) method with electrospray ionization in positive mode. The separation was performed with a Zorbax C-18 column using a binary gradient elution of 0.05% formic acid acetonitrile/0.05% formic acid water. According to the MS spectra and after comparison with reference standards and literature reports, hydroxylation, dehydrogenation or D-ring hydrolysis metabolites of TIIA and Cry but not of TI were characterized, which coincided with those reported using regular <em>in vivo</em> or <em>in vitro</em> metabolic analysis methods, thus verifying that zebrafish can successfully imitate mammalian phase I metabolism which instills further confidence in using zebrafish as a novel and prospective metabolism model.

Keywords

• zebrafish
• phase I metabolism
• tanshinone IIA
• cryptotanshinone
• tanshinone I
• Radix Salvia miltiorrhiza