Metabolic profiling of RB-2 and RB-4, two analogs of polyacetylene from Bupleurum.

RB-2 and RB-4 are two structural analogs of polyacetylene from Radix Bupleuri that show antidepressant effects. However, no metabolic data are available to elucidate their systemic homeostasis. Mass spectrometry combined with liver microsomes and recombinant drug-metabolizing enzymes were performed to profile the biotransformations of RB-2/RB-4 in vitro and in vivo. Oxidation should be the major metabolic pathways for them in phase I, while CYP2C9 and CYP2E1 was the major contributor. In phase II, conjugational groups usually combined with the metabolites from phase I. This study provides an important reference basis for the safety evaluation and rational application of RB-2/RB-4.