Metabolism and toxicity of usnic acid and barbatic acid based on microsomes, S9 fraction, and 3T3 fibroblasts in vitro combined with a UPLC-Q-TOF-MS method.

ABSTRACT: Introduction: Usnic acid (UA) and barbatic acid (BA), two typical dibenzofurans and depsides in lichen, have a wide range of pharmacological activities and hepatotoxicity concerns. This study aimed to clarify the metabolic pathway of UA and BA and illuminate the relationship between metabolism and toxicity. Methods: An UPLC-Q-TOF-MS method was developed for metabolite identification of UA and BA in human liver microsomes (HLMs), rat liver microsomes (RLMs), and S9 fraction (RS9). The key metabolic enzymes responsible for UA and BA were identified by enzyme inhibitors combined with recombinant human cytochrome P450 (CYP450) enzymes. The cytotoxicity and metabolic toxicity mechanism of UA and BA were determined by the combination model of human primary hepatocytes and mouse 3T3

SUBMITTER: Wang H 

PROVIDER: S-EPMC10308081 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature