Effects of Animal Strain, Dose, and Cotreatment with Saikosaponin b2 on the Pharmacokinetics of Saikosaponin a in Rats
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Background and Objectives
Radix Bupleuri (RB, Chaihu in Chinese) has been used as a traditional medicine for more than 2000 years in China, Japan, Korea, and other Asian countries. Saikosaponin a (SSa), the most abundant saikosaponin in RB, exhibits various pharmacological activities, including anti-inflammatory, antitumor, antiviral, immunoregulatory, neuromodulatory, and hepatoprotective activities. A comprehensive study of the pharmacokinetic characteristics of SSa is needed to gain a detailed understanding of its pharmacodynamic mechanism.
Here, we determined the effects of rat strain (Sprague Dawley and Wistar), oral dose, and cotreatment with saikosaponin b2 (SSb2) on the pharmacokinetics of SSa by measuring SSa in plasma via LC–MS/MS.
The results showed that the absorption of SSa in Wistar rats was statistically superior to its absorption in Sprague Dawley rats based on pharmacokinetic parameters such as the area under the concentration–time curve (AUC0–t) and the peak concentration (Cmax). Pharmacokinetic studies of different doses of SSa in Wistar rats revealed that the systemic exposure of SSa, based on AUC values, increased disproportionately with dose, indicating that SSa exhibits non-dose-proportional pharmacokinetics. In addition, our studies showed that SSb2, a characteristic component of vinegar-baked Radix Bupleuri (VBRB), inhibits the absorption of SSa in rats.
The pharmacokinetic data for SSa obtained in this study will play an important role in attempts to better understand the fate of SSa in rats and to explore how these saikosaponins are likely to exert their pharmacological effects in vivo. In addition, further research is needed to elucidate the interactions of saikosaponins with metabolic enzymes and transporters in order to account for the phenomena observed in this study.
Compliance with Ethical Standards
This project was financially supported by the National Natural Science Foundation of China (no. 8157362), the Open Project Program of Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards (no. 201503), the Natural Research Foundation of Jiangsu Province (no. BK20161456), and the Qing Lan Project of Jiangsu Province (2017).
Conflict of interest
All the authors have no conflict of interest to declare.
The animal experiments were approved by the ethical committee of China Pharmaceutical University and were carried out in accordance with the US guidelines for the care and use of laboratory animals.
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