Investigation on the Metabolism of Curcumin and Baicalein in Zebrafish by Liquid Chromatography-tandem Mass Spectrometry Analysis

Background: Curcumin (CUR) and baicalein (BAI) are the main active ingredients in Curcuma longa and Scutellaria baicalensis, which are used together in Jiang-Qin-Si-Wu decoction to treat gynecological diseases. On the other hand, zebrafish, as a metabolic model has become more popular, therefore, the metabolism of CUR and BAI in zebrafish is investigated in the present study. Methods: Zebrafish embryos after hatching 48 hours were divided into four experimental groups. The blank group was exposed to 1 mL of ultra-pure water. Three drug-treated groups were exposed to CUR (8 μM, 1 mL), BAI (8 μM, 1 mL), CUR and BAI (8 μM, 2 mL), respectively. After homogenization, they were analyzed by liquid chromatography-tandem mass spectrometry (LCMS/ MS). The structure of the metabolites was determined by comparing their corresponding mass spectra with those of relevant literature. According to the change of metabolite content, the metabolic effect of curcumin and baicalein was explored. Results: Five and six metabolites of CUR and BAI in zebrafish were identified by LC-MS/MS, respectively. Their metabolic pathways in zebrafish were glucuronidation and sulfation. Reduction and methylation reactions also occurred for CUR and BAI, respectively. In addition, after combined exposure of both the drugs, CUR reduced the BAI glucuronide metabolites and inhibited the metabolism of BAI in zebrafish, which is consistent with the mammalian metabolism. Conclusion: Using LC-MS/MS analysis, zebrafish is a feasible model for drug metabolism study. The results of metabolic study indicated that CUR might affect the therapeutic effect of BAI.