UPLC-QTOF-MS Based Comparison of Rotundic Acid Metabolic Profiles in Normal and NAFLD Rats

Abstract

Rotundic acid, the principal bioactive constituent of the herbal remedy “Jiubiying”, has been considered as a candidate compound for treating non-alcoholic fatty liver disease (NAFLD). However, the in vivo and in vitro metabolism of rotundic acid has remained unclear. With the aim of elucidating its metabolic profile, a reliable approach that used ultra-high performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was applied for screening and identifying rotundic acid in vivo (plasma, feces, urine, and liver tissue of normal and NAFLD model rats) and in vitro (rat liver microsomes) metabolites. Herein, 26 metabolites of rotundic acid were identified, including 22 metabolites in normal rats, 20 metabolites in NAFLD model rats, and eight metabolites in rat liver microsomes. Among them, 17 metabolites were identified for the first time. These data illustrate that the pathological status of NAFLD affects the metabolism of rotundic acid. Furthermore, the major pathways of metabolism included phase Ⅰ (demethylation, desaturation, etc.) and phase Ⅱ (sulfation and glucuronidation) reactions, as well as a combined multiple-step metabolism. This work provides important information on the metabolism of rotundic acid and lays the foundation for its future clinical application.

Efficacy of Rotundic Acid and Its Derivatives as Promising Natural Anticancer Triterpenoids: A Literature‐Based Study

“…[74] A different study reported that the main metabolic pathways for RA include demethylation, desaturation, hydroxylation, reduction, sulfation, and glucuronidation. [75] The study also found that RA is eliminated rapidly, with a half-life (t1/2) of nearly 2 hours. [74] Table 1.…”

“…The study also found that co‐administration of RA with verapamil could enhance the absorption of RA by suppressing the effect of P‐gp in a Caco‐2 cell model, as well as slow down the metabolism of RA in the liver of rats by suppressing the activity of CYP3A [74] . A different study reported that the main metabolic pathways for RA include demethylation, desaturation, hydroxylation, reduction, sulfation, and glucuronidation [75] . The study also found that RA is eliminated rapidly, with a half‐life (t1/2) of nearly 2 hours [74] …”