The Influence of Compatibility of Rhubarb and Radix Scutellariae on the Pharmacokinetics of Anthraquinones and Flavonoids in Rat Plasma
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Background and Objectives
Rhubarb–Radix scutellariae is a classic herb pair, which is commonly used to clear away heat and toxin in clinic. The aim of this study was to investigate the influence of compatibility of Rhubarb and Radix scutellariae on the pharmacokinetic behaviors of anthraquinones and flavonoids in rat plasma.
Eighteen rats were randomly divided into three groups, and were orally administered Rhubarb and/or Radix scutellariae extracts. A sensitive and rapid UPLC–MS/MS method was developed and validated to determine the concentrations of baicalin, baicalein, wogonside, wogonin, rhein, and emodin in rat plasma. The concentrations of phase II conjugates of flavonoid aglycones and anthraquinone aglycones were also determined after hydrolyzing the plasma with sulfatase.
Compared with administration of Radix scutellariae alone, co-administration of Rhubarb significantly decreased the first maximum plasma concentration (C max1) of baicalin, wogonside, and the phase II conjugates of baicalein, wogonin to 46.40, 61.27, 41.49, and 20.50%, respectively. The area under the plasma concentration–time curve from time zero to infinity (AUC0–∞) was significantly decreased from 82.60 ± 20.22 to 51.91 ± 7.46 μM·h for rhein and 276.83 ± 98.02 to 175.42 ± 86.82 μM·h for the phase II conjugates of wogonin after compatibility. The time to reach the first maximum plasma concentration (T max1) of anthraquinones was shortened and the second peak of anthraquinones disappeared after compatibility.
Compatibility of Rhubarb and Radix scutellariae can significantly affect the pharmacokinetic behaviors of characteristic constituents of the two herbs. The cause of these pharmacokinetic differences was further discussed combined with the in vivo ADME (absorption, disposition, metabolism, and excretion) processes of anthraquinones and flavonoids.
Compliance with Ethical Standards
This project was financially supported by the National Natural Science Foundation of China (No. 81403314), the Open Project Program of Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards (No. 201503), and the Natural Research Foundation of Jiangsu Province (No. BK20161456) and the Qing Lan Project of Jiangsu Province (2017).
Conflict of interest
The authors declare that there is no conflict of interest.
The ethical committee of China Pharmaceutical University approved the experiment. The experiment was carried out in accordance with the US guidelines for the Care and Use of Laboratory Animals.
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