- 作者：Hao Sun ; Guangwen Luo ; Zheng Xiang ; XZH0077@126.com" class="auth_mail" title="E-mail the corresponding author ; Xiaojun Cai ; Dahui Chen
- 关键词：Metabolomics ; Pharmacokinetic ; Pharmacodynamic ; Rhein ; Rhubarb
- 刊名：Phytomedicine
- 出版年：2016
- 出版时间：1 December 2016
- 年：2016
- 卷：23
- 期：13
- 页码：1661-1670
- 全文大小：852 K
Purpose
Three effect indicators of renal fibrosis were successfully determined. The relationship between pharmacokinetics and pharmacodynamics of rhein in rhubarb was elucidated.
Study design
The study was a metabolomics analysis of rat plasma and pharmacokinetics/ pharmacodynamics of rhein.
Methods
A sensitive and simple ultra performance liquid chromatography-tandem triple quadrupole mass spectrometry (UPLC-MS/MS) method was applied to determine the rhein plasma concentration in the rat model of renal fibrosis and rat sham-operated group after the administration of rhubarb decoction. Then, the ultra performance liquid chromatography-Micromass quadrupole-time of flight mass spectrometry (UPLC-QTOF/MS) metabolomics method was used to screen biomarkers of renal fibrosis in rat plasma. Furthermore, the relationship between the plasma concentration of rhein and the concentration of three biomarkers directly related to renal fibrosis were analyzed.
Results
The three screened biomarkers could represent the effect of rhein treatment on renal fibrosis. Increasing the plasma concentration of rhein tended to restore the concentration of the three biomarkers in the model group compared with that in the sham-operated group. Evident differences in the area under the plasma concentration-time curve (AUC) of rhein were also observed under different pathological states. The results provide valuable information for the clinical application of rhubarb.
Conclusion
Rhein intervention could recover the physiological balance in living organisms from the pharmacokinetic/pharmacodynamic levels. New information on the pharmacokinetic/pharmacodynamic study of complex diseases is provided.