Abstract
Rotundic acid and pedunculoside are the most abundant constituents in Ilicis Rotundae
Cortex, and possess lipid-lowering activity. In this study, we evaluated the pharmacokinetic
interactions of rotundic acid with pedunculoside and other ingredients from Ilicis
Rotundae Cortex with rotundic acid and pedunculoside, and preliminarily investigated
the effects of gut microbiota on their pharmacokinetics using a pseudo-germ-free rat
model. After a single oral administration of each monomer, a monomer mixture, and
Ilicis Rotundae Cortex extract to the conventional and pseudo-germ-free rats, rotundic
acid and pedunculoside were quantified in plasma by an UPLC/Q-TOF-MS/MS method. The
systemic exposure (maximum plasma concentration and area under concentration-time
curve) of two analytes in conventional rats were increased in an approximately dose-dependent
manner. Oral administration of rotundic acid and pedunculoside in the forms of a monomer
mixture and Ilicis Rotundae Cortex extract to the conventional rats significantly
decreased the systemic exposure compared with the monomer groups, which demonstrated
the existence of significant pharmacokinetic interactions. The pseudo-germ-free rats
were prepared by nonabsorbable antibiotic treatment, and the systemic exposure of
two analytes were significantly decreased and most of the “time to reach the maximum”
values were delayed in comparison to conventional rats, therefore gut microbiota might
serve as an efficient absorption promoter. These results provide a scientific basis
for the clinical application of the two bioactive constituents and Ilicis Rotundae
Cortex.
Key words
Ilex rotunda
- Aquifoliaceae - Ilicis Rotundae Cortex - rotundic acid - pedunculoside - pharmacokinetic
interactions - gut microbiota - antibacterial
