title: Metabolism of calycosin, an isoflavone from Astragali Radix, in zebrafish larvae.
abstract: Although zebrafish has become a popular animal model for drug discovery and screening, drug metabolism in zebrafish remains largely unknown. In this study, we probed the metabolic capability of zebrafish larvae with calycosin, one of the major isoflavone constituents of Radix Astragali that was previously demonstrated to be angiogenic in the zebrafish model.        The metabolism of calycosin and accumulation of its metabolites in zebrafish larvae were determined using an LC-MS/MS method.        Calycosin showed a slow but steady decrease from the culture medium as well as a steady accumulation in zebrafish larvae. Calycosin underwent major conjugation and minor oxidation in zebrafish larvae. A total of ten calycosin metabolites formed from glucuronidation, glucosylation, sulfation, oxidation or a combination of two of these metabolisms were identified, most of which were reported for the first time. Most metabolites increased steadily in the larvae over 24-h experimental period.        The dominant phase II conjugation of calycosin in zebrafish larvae matched well with existing knowledge of isoflavone metabolism in mammalians. The findings shed a light in certain degree of similarity of phase II drug metabolism between zebrafish larvae and mammals and warrant further investigation on feasibility of adopting the zebrafish larvae as a whole-organism model for examining drug metabolism.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Hu
authors.forename: Shiu On
authors.initials: SO
authors.lastname: Siu
authors.forename: Shang
authors.initials: S
authors.lastname: Li
authors.forename: Ivan Keung
authors.initials: IK
authors.lastname: Chu
authors.forename: Yiu Wa
authors.initials: YW
authors.lastname: Kwan
authors.forename: Shun Wan
authors.initials: SW
authors.lastname: Chan
authors.forename: George Pak-Heng
authors.initials: GP
authors.lastname: Leung
authors.forename: Ru
authors.initials: R
authors.lastname: Yan
authors.forename: Simon Ming-Yuen
authors.initials: SM
authors.lastname: Lee
mesh_terms: D000818:Animals; D027883:Astragalus Plant / Q000737:chemistry; D027885:Astragalus propinquus; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D003470:Culture Media / Q000737:chemistry; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D007529:Isoflavones / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D007814:Larva / Q000187:drug effects / Q000378:metabolism; D013058:Mass Spectrometry; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D013997:Time Factors; D015027:Zebrafish / Q000378:metabolism*
chemical_list: D003470:Culture Media; D004365:Drugs, Chinese Herbal; D007529:Isoflavones; C121707:7,3'-dihydroxy-4'-methoxyisoflavone; C027492:Huang Qi