rutundic-acid and pedunculoside

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.

Topics: Administration, Oral; Animals; Calibration; Chromatography, Liquid; Drugs, Chinese Herbal; Gastrointestinal Microbiome; Glucose; Herb-Drug Interactions; Male; Rats, Sprague-Dawley; Tandem Mass Spectrometry; Triterpenes

Triterpenoids, the major bioactive ingredients of Ilicis Rotundae Cortex, contributes a significant cardiovascular protection activity. Although many studies about the total saponins have been reported, the absorption triterpenoids and pharmacokinetic behaviors were unclear. Thus, the present study aims to comprehensive elucidate the absorption triterpenoids and their pharmacokinetics in rats after oral administration the crude extract using UPLC/Q-TOF-MS/MS. A total of forty-two triterpenoids were successfully characterized from the rat plasma, and thirty-two of them were validated by the reference substances, while the others were tentatively identified based on the mass spectral fragmental patterns. Furthermore, the plasma concentrations of six absorption bioactive triterpenoids (rotundinoside C, ilexoside O, pedunculoside, rotundic acid, rotundanonic acid and ilexgenin A) were simultaneously quantified by selected reaction monitoring in negative ionization mode. All analytes exhibited good linearity with correlation coefficients values greater than 0.99 and the LLOQ ranged from 1.2 to 3.2 ng/mL, and method validation for selectivity, precision, accuracy, recovery, matrix effect and stability were reckoned acceptable. The results were successfully applied for the multiple-component pharmacokinetic study of the six bioactive triterpenoids.

Topics: Administration, Oral; Animals; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Glucose; Ilex; Male; Molecular Structure; Plant Extracts; Rats; Rats, Sprague-Dawley; Saponins; Tandem Mass Spectrometry; Triterpenes

To establish an HPLC-ELSD method for the quantification of pedunculoside, ziyuglycoside I and rutundic acid, in the leaves of Ilex purpurea Hassk.. By optimizing the chromatographic conditions of HPLC and the parameters of ELSD to study the methodology. Column: Allsphere ODS-2 (250 mm x 4.6 mm ID, 5 microns), mobile phase: methanol-water (59:41), flow rate: 1.0 mL.min-1, drift tube temperature: 59 degrees C, gas flow rate: 2.38 L.min-1.. The calibration curves were linear in the range of 2.56-25.60 micrograms for pedunculoside, 1.64-16.40 micrograms for ziyuglycoside I and 3.74-37.40 micrograms for rutundic acid. The average recovery of pedunculoside was 96.3%, RSD 1.59% (n = 5), ziyuglycoside I 97.3%, RSD 3.82% (n = 5), rutundic acid 97.7%, RSD 2.11% (n = 5). All of RSDs of the precision were less than 4% (n = 6), and the reproduciblities less than 5% (n = 6).. The method is simple, accurate, effective and feasible. It can be used for the determination of the contents of pedunculoside, ziyuglycoside I and rutundic acid in leaf of Ilex purpurea Hassk.

Topics: Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Glucose; Ilex; Plant Leaves; Plants, Medicinal; Saponins; Triterpenes