Pharmacokinetics, tissue distribution and excretion of five rhubarb anthraquinones in rats after oral administration of effective fraction of anthraquinones from rheum officinale

Abstract

1. Rhubarb, a famous traditional Chinese medicine, shows a wide range of physiological activities and pharmacological benefits. Rhubarb anthraquinones are perceived as the pharmacologically active compounds of Rhubarb, and understanding metabolism of them is crucial to assure safety and effectiveness of clinical application. In this study, the pharmacokinetics, tissue distribution and excretion of five rhubarb anthraquinones (aloe-emodin, rhein, emodin, chrysophanol, physcion) were systematically investigated after oral administration of rhubarb extract to rats.

2. An HPLC method was developed and validated for quantitation of five rhubarb anthraquinones in rat plasma, tissues, urine and faeces to investigate the Pharmacokinetic characteristics. The results showed that the proposed method was suitable for the quantification of five anthraquinones in plasma, tissue and excreta samples with satisfactory linear (r > 0.99), precision (<10%) and recovery (85.12–104.20%). The plasma concentration profiles showed a quick absorption with the mean T_max of 0.42–0.75 h and t_1/2 of 6.60–15.11 h for five anthraquinones. The analytes were widely distributed in most of the tissues. Approximately 0.13–10.59% and 28.47–81.14% of five anthraquinones were recovered in urine and faeces within 132 h post-dosing, which indicated the major elimination route was faeces excretion.

3. In summary, this study lays a foundation for elucidating the pharmacokinetic rule of rhubarb anthraquinone and the important data can provide reliable scientific resource for further research.

Keywords:

• Rhubarb extract
• anthraquinones
• pharmacokinetics
• tissues distribution
• excretion

Acknowledgements

The authors thanks all the volunteers involved in the study and all the people in the Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases co-constructed by Henan province & Education Ministry of P.R. China for their help. Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases co-constructed by Henan province & Education Ministry of P. R. China and Zhengzhou Key Laboratory of Chinese Medicine Quality Control and Evaluation contributed to the study design, research, interpretation of data, and the writing, reviewing, approving of the publication. The authors declare no conflict of interest.

Disclosure statement

The authors report no declarations of interest.

Additional information

Funding

This research was supported financially by Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases co-constructed by Henan province & Education Ministry of P.R. China and Zhengzhou Key Laboratory of Chinese Medicine Quality Control and Evaluation (project number: 20A360007, the Henan University of Traditional Chinese Medicine PhD Fund Support [BSJJ-2016-01]).