1. Zebrafish has been used in metabolic study of drugs as a powerful tool in recent years. In this study, we make a feasible metabolism investigation of five protoberberine alkaloids (PBAs) applied in zebrafish model for the first time, including berberine (BBR), palmatine (PAL), jatrorrhizine (JAT), coptisine (COP) and epiberberine (EBBR). 2. After exposure for 24 hours, 19 metabolites were identified by LTQ Orbitrap mass spectrometer, including 9 phase I metabolites and 10 phase II metabolites. Demethylation, hydroxylation, sulfation and glucuronidation were the major metabolic transformation of PBAs in zebrafish, which were similar to mammals. Compared with reported literatures, BBR and JAT showed high consistency between human and zebrafish in metabolic pathways. 3. To our knowledge, this is the first time to study in vivo metabolism of COP, which provides useful information to other researchers. 4. This study indicated that zebrafish model is feasible and reasonable to predict the metabolism of PBAs. It showed great potential for developing a novel and rapid method for predicting the metabolism of trace compounds of botanical drugs, with the advantages of lower cost, higher performance and easier set up.

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Aristolochic acid I (AAI) was regarded as the major toxic component of aristolochic acid (AA). In addition to aristolochic acid nephropathy (AAN), liver cancers induced by AAI has aroused increasing attention recently. In this paper, the discovery of diagnostic biomarkers for AAI-induced liver injury has been studied, especially for the lipid markers. From the histopathological characteristics, the injury was observed clearly in the liver apart from the kidney after 30 mg/kg of AAΙ treatment for one week, while the lesion alleviated after AAΙ discontinuance. The serum biochemical indexes were manifested to the normal tendency after AAΙ discontinuance for two weeks. According to the evaluation of pathology slices and serum biochemical indexes, they indicated that the hepatotoxicity induced by AAΙ was reversible to some extent. A total of 44 lipid markers were identified in the liver, as well as 59 in the serum. Twenty-six common lipid markers were observed in both serum and liver. Furthermore, nine out of 26 lipids exhibited the excellent diagnostic ability to differentiate the control group from the AAΙ group and AAΙ discontinuance group with high sensitivity and specificity. The changed lipid markers might serve as characteristics to explain the mechanisms of pathogenesis and progression in hepatotoxicity induced by AAΙ.

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