Study on the Impact of β-CD Inclusion Complex on the In vivo Metabolism of Ginsenoside Re: A Pharmacokinetic, Metabolite Analysis, and Tissue Distribution Investigation in a Rat Model.

Triol-type ginsenoside Re (GS-Re) exhibits potent anti-myocardial ischemia-reperfusion effects, but its clinical use is hindered by poor bioavailability. This study evaluates the impact of β-cyclodextrin (β-CD) inclusion on GS-Re bioavailability and tissue dynamics in rat models. The GS-Re-β-CD complex was prepared using aqueous stirring and characterized. Male Wistar rats (200 ± 20 g) were administered GS-Re at a dose of 500 mg/kg. Plasma concentrations were quantified using UHPLC-MS/MS to evaluate pharmacokinetics and analyze metabolites in tissues and feces. Compared to the group receiving GS-Re alone, the GS-Re-β-CD inclusion complex exhibited significantly improved pharmacokinetic characteristics in rats: Maximum concentration (Cmax) increased by 1.86-fold. Area under the curve (AUC) increased by 2.09-fold. Time to reach peak concentration (T) was reduced, while the half-life (t) was extended, suggesting a faster and prolonged absorption of GS-Re. Metabolite analysis showed higher concentrations of Rg1, Rg2, Rh1, F1, PPT, and Re in tissues with GS-Re-β-CD, while metabolite types remained unchanged. The inclusion of β-CD significantly enhanced the bioavailability and tissue concentration of GS-Re, as demonstrated by increased C and AUC, along with a shorter T and longer t. These findings suggest that β-CD inclusion could be an effective strategy to improve the clinical applicability of GS-Re, providing valuable pharmacokinetic and tissue concentration insights for further development.