Metabolic and Pharmacokinetic Investigation of Ilexsaponin A₁ in Normal and Antibiotic-treated Rats

Abstract

Background Ilexsaponin A1 (IA1) is a bioactive triterpene saponin derived from natural medicinal plants. IA1 exhibits anti-inflammatory and proangiogenic activities and improves intestinal barrier function. It has been reported that IA1 could be metabolized into a dominant metabolite, ilexgenin A (IA) by β-glucosidase enzymes in intestinal microflora. Materials and Methods Herein, an accurate, sensitive, and selective method based on ultra-performance liquid chromatography coupled with mass spectrometry was established to simultaneously profile the metabolism and pharmacokinetic behaviors of IA1 in normal and antibiotic-treated rat plasma after intragastric administration of IA1. The precursor-to-product ion pairs of IA and IA1 were m/ z 501.32↓439.32 and m/ z 663.38↓501.32, respectively. For method validation, the specificity, matrix effect, accuracy, precision, and stability of the pharmacokinetic study were measured, and a calibration curve was created. The collaborative pharmacological target pathways of IA1 and its metabolite IA were investigated using network pharmacology tools. Results The validated analytical method was successfully utilized to investigate the pharmacokinetics of IA1 in normal and antibiotic-treated rats. The bioavailability of IA1 and conversion from IA1 to IA were significantly inhibited by antibiotic-treated rats after oral administration of IA1. Fragment ions at m/z 483.3155, 455.3159, 439.3233, 421.3136, 395.3362, 152.9952, 113.0256, and 71.0531 were characteristic of the IA1 moiety. IA1 was metabolized in rat plasma by biotransformation routes involving deglycosylation, decarboxylation, isomerization, hydrogenation, dehydrogenation, and oxidation. Considering database analysis, IA and IA1 play synergistic role in common pharmacological pathways, such as hypertrophic cardiomyopathy and dilated cardiomyopathy. Conclusion The experiments illustrated that β-glucosidase activity inhibited by antibiotics suppressed the hydrolysis reaction of IA1 in the intestinal tract. IA1 and IA play a synergistic role in exerting effects.

The Increased Dissolution and Oral Absorption of Itraconazole by Nanocrystals with an Endogenous Small-Molecule Surfactant as a Stabilizer

“…An in vivo pharmacokinetic study was conducted in rats. Figure 8 illustrates the mean plasma concentration-time (C-t) profiles for ITZ following oral administration at a single dose of 15 mg/kg [8,39], where the mean plasma concentration was a value fitted using DAS 2.0 software. It was obvious that the pharmacokinetic profile of the ITZ-Nano group was different in the peak concentration and peak time from the pellet group.…”