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Metabolism of Tanshinone IIA, Cryptotanshinone and Tanshinone I from Radix Salvia Miltiorrhiza in Zebrafish
Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, 100 Shizi Street, Nanjing 210028, China
State Key Laboratory of Natural Medicines and Department of Pharmacognosy, China Pharmaceutical University, 24 Tongjia Lane, Nanjing 210009, China
Biology & Medicine Science and Technology Industry Park of Weifang Hi-Tech Development Zone, Crossroads of Jiankang East Street and Gaoxin Road 2, Weifang 261061, China
* Authors to whom correspondence should be addressed.
Received: 25 June 2012; in revised form: 9 July 2012 / Accepted: 10 July 2012 / Published: 18 July 2012
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 in vivo or in vitro 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
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Wei, Y.; Li, P.; Wang, C.; Peng, Y.; Shu, L.; Jia, X.; Ma, W.; Wang, B. Metabolism of Tanshinone IIA, Cryptotanshinone and Tanshinone I from Radix Salvia Miltiorrhiza in Zebrafish. Molecules 2012, 17, 8617-8632.
Wei Y, Li P, Wang C, Peng Y, Shu L, Jia X, Ma W, Wang B. Metabolism of Tanshinone IIA, Cryptotanshinone and Tanshinone I from Radix Salvia Miltiorrhiza in Zebrafish. Molecules. 2012; 17(7):8617-8632.
Wei, Yingjie; Li, Ping; Wang, Changmei; Peng, Yunru; Shu, Luan; Jia, Xiaobin; Ma, Wenquan; Wang, Bing. 2012. "Metabolism of Tanshinone IIA, Cryptotanshinone and Tanshinone I from Radix Salvia Miltiorrhiza in Zebrafish." Molecules 17, no. 7: 8617-8632.