A comparative study of aurantio-obtusin metabolism in normal and liver-injured rats by ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry.

ABSTRACT

Aurantio-obtusin, an anthraquinone isolated from cassiae semen, possesses diverse pharmacological activities, including hypotensive, hypolipidemic and anti-inflammatory effects. However, our previous studies demonstrated that exposure to aurantio-obtusin induced hepatotoxicity, but the mechanisms of the toxic effects remain unknown. The purpose of the present study is to establish a strategy for the metabolite profiling of aurantio-obtusin in normal and liver-injured rats. This study aimed at identifying the in vivo metabolites and the metabolic profiling in rats after oral administration at a dose of aurantio-obtusin (4 and 200 mg/kg) by using an ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and metabolynx™ software. A total of 39 metabolites were detected and 3 of them were compared with standard substances. The results indicated that the principal metabolism pathways of aurantio-obtusin in normal rats were glucuronidation and sulfation, while in rats with liver injury, demethylation, dehydroxylation and reduction were also observed and regarded as new metabolic patterns of aurantio-obtusin. These findings helped us to understand the pharmacological and toxicological mechanisms of aurantio-obtusin. Moreover, this study could help to elucidate the metabolic profiling of other anthraquinones.