Background: Tanshinone IIA (TIIA), protocatechuic aldehyde (PA), danshensu (DSS), salvianolic acid B (SAB) and hydroxysafflor yellow A (HSYA) are the major components of Salvia miltiorrhiza Bge. (Danshen) and Carthamus tinctorius L. (Honghua) herbal pair. These active components may contribute to the potential synergistic effects of the herbal pair.

Objective: This study aimed to investigate the metabolites of TIIA, PA, DSS, SAB and HSYA in zebrafish, and to explore the influence of HSYA on the metabolism of TIIA, PA, DSS, and SAB.

Method: 48 h post-fertilization zebrafish embryos were exposed either to each compound alone, TIIA (0.89 μg/mL), PA (0.41 μg/mL), DSS (0.59 μg/mL), SAB (2.15 μg/mL), and HSYA (1.83 μg/mL) and in combination with HSAY (1.83 μg/mL). The metabolites of TIIA, PA, DSS, SAB, and HSYA in zebrafish were characterized using high-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) and quantitatively determined by HPLC-MS with single and combined exposure.

Results: Among the 26 metabolites detected and characterized from these five compounds, methylation, hydroxylation, dehydrogenation, hydrolysis, sulfation and glucuronidation were the main phase I and phase II metabolic reactions of these compounds, respectively. Furthermore, the results showed that HSYA could either enhance or reduce the amount of TIIA, PA, DSS, SAB, and their corresponding metabolites.

Conclusion: The results provided a reference for the study on drug interactions in vivo. In addition, the zebrafish model which required much fewer amounts of test samples, compared to regular mammal models, had higher efficiency in predicting in vivo metabolism of compounds.

背景：丹参酮IIA（TIIA），原儿茶醛（PA），丹参素（DSS），丹酚酸B（SAB）和羟基红花黄A（HSYA）是丹参中的主要成分。（丹参）和红花（红花）草药对。这些活性成分可能有助于草药对的潜在协同作用。

目的：本研究旨在研究斑马鱼中TIIA，PA，DSS，SAB和HSYA的代谢产物，并探讨HSYA对TIIA，PA，DSS和SAB代谢的影响。

方法：将受精后48小时的斑马鱼胚胎分别暴露于每种化合物，TIIA（0.89μg/ mL），PA（0.41μg/ mL），DSS（0.59μg/ mL），SAB（2.15μg/ mL）和HSYA（1.83μg/ mL）以及与HSAY（1.83μg/ mL）的组合。使用高效液相色谱/串联质谱（HPLC-MS / MS）对斑马鱼中TIIA，PA，DSS，SAB和HSYA的代谢产物进行表征，并通过HPLC-MS定量测定其单次或多次接触。

结果：从这五种化合物中检测到并表征的26种代谢物中，甲基化，羟基化，脱氢，水解，硫酸化和葡萄糖醛酸化分别是这些化合物的主要I相和II相代谢反应。此外，结果表明，HSYA可以增强或减少TIIA，PA，DSS，SAB及其相应代谢产物的量。

结论：该结果为体内药物相互作用的研究提供了参考。另外，与常规哺乳动物模型相比，需要大量测试样品的斑马鱼模型在预测化合物的体内代谢方面具有更高的效率。