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

IF 4.3 3区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutical Sciences Pub Date : 2025-01-08 DOI:10.1016/j.ejps.2025.107004

Hui Li , Rui Liu , Yuxin Guo , Anqi Wang , Ting Zhou , Shuhang Wang , Wei Wu

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Abstract

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_{0–24 h}) increased by 2.09-fold. Time to reach peak concentration (T_max) was reduced, while the half-life (t_1/2) 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_max and AUC, along with a shorter T_max and longer t_1/2. 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.

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β-CD包合物对人参皂苷Re体内代谢影响的研究：大鼠模型药代动力学、代谢物分析及组织分布研究

三醇型人参皂苷Re （GS-Re）具有较强的抗心肌缺血再灌注作用，但其生物利用度较差，阻碍了其临床应用。本研究评估了β-环糊精（β-CD）包合物对大鼠GS-Re生物利用度和组织动力学的影响。采用水搅拌法制备了GS-Re-β-CD配合物，并对其进行了表征。雄性Wistar大鼠（200±20 g）按500 mg/kg剂量给予GS-Re。采用高效液相色谱-质谱联用技术（UHPLC-MS/MS）定量测定血药浓度，评估药代动力学并分析组织和粪便中的代谢物。与单独给药组相比，GS-Re-β-CD包合物在大鼠体内的药动学特征明显改善，最大浓度（Cmax）提高了1.86倍。曲线下面积（AUC0-24h）增加2.09倍。达到峰值浓度的时间（Tmax）减少，半衰期（t1/2）延长，表明GS-Re的吸收速度更快，时间更长。代谢物分析显示，GS-Re-β-CD组组织中Rg1、Rg2、Rh1、F1、PPT和Re浓度较高，代谢物类型保持不变。β-CD的加入显著提高了GS-Re的生物利用度和组织浓度，增加了Cmax和AUC，缩短了Tmax，延长了t1/2。这些发现表明，β-CD包埋可能是提高GS-Re临床适用性的有效策略，为进一步开发提供了有价值的药代动力学和组织浓度信息。

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来源期刊

European Journal of Pharmaceutical Sciences 医学-药学

CiteScore

9.60

自引率

2.20%

发文量

248

审稿时长

50 days

期刊介绍： The journal publishes research articles, review articles and scientific commentaries on all aspects of the pharmaceutical sciences with emphasis on conceptual novelty and scientific quality. The Editors welcome articles in this multidisciplinary field, with a focus on topics relevant for drug discovery and development. More specifically, the Journal publishes reports on medicinal chemistry, pharmacology, drug absorption and metabolism, pharmacokinetics and pharmacodynamics, pharmaceutical and biomedical analysis, drug delivery (including gene delivery), drug targeting, pharmaceutical technology, pharmaceutical biotechnology and clinical drug evaluation. The journal will typically not give priority to manuscripts focusing primarily on organic synthesis, natural products, adaptation of analytical approaches, or discussions pertaining to drug policy making. Scientific commentaries and review articles are generally by invitation only or by consent of the Editors. Proceedings of scientific meetings may be published as special issues or supplements to the Journal.