Transcriptional regulation of THSG and anthraquinones in tubers of Polygonum multiflorum based on human progesterone X receptor (PXR) mediated CYP3A4 rapid screening system

ZHANG Zhao-yan1,2 YANG Liang2 HUANG Xiao-yan2,3 WANG Mei-xi2 MA Zeng-chun2 TANG Xiang-lin2 WANG Yu-guang2 GAO Yue1,2

(1.College of Life Science and Bioengineering, Beijing University of Technology, Beijing, China 100124)
(2.Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing, China 100850)
(3.Tianjin University of Traditional Chinese Medicine, Tianjin, China 300193)

【Abstract】The rapid screening technology was used to investigate the transcriptional regulation effect of main chemical constituents in tubers of Polygonum multiflorum, including 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucopyranoside (THSG) and anthraquinones (such as rhein, chrysophanol, aloe-emodin, emodin) on CYP3A4 mediated by human pregnancy X receptor (PXR). The effect of chemical compositions on the cell activity was detected by MTS cell viability assay. IC50 was calculated. The expression vector and the reporter vector were co-transfected into Hep G2 cells, with 10 μmol·L−1 rifampicin (RIF) as a positive control, and 10 μmol·L−1 ketoconazole (TKZ) as a negative control. After being treated with different concentrations of anthraquinones (2.5, 5, and 10 μmol·L−1) for 24 h, the cells were tested for dual luciferase activity. The results showed that the inhibitory effects of THSG, chrysophanol, emodin, rhein and aloe-emodin on CYP3 A4 were inhibited by co-transfection of pc DNA3.1 and p GL4. 17-CYP3 A4. The expressions of pc DNA3.14-PXR and p GL4.17-CYP3 A4 were induced by the four compounds. Besides, emodin had a direct inducing effect. In conclusion, the four anthraquinone compounds have an inducing effect on CYP3 A4 by PXR, but emodin can directly induce CYP3 A4. THSG can inhibit CYP3 A4, but plasmid can induce CYP3 A4 after intervened with PXR. These results suggest that we should pay attention to the liver function and avoid liver damage in the combined administration of drugs.

【Keywords】 Polygonum multiflorum; THSG; anthraquinones; human progesterone X receptor (PXR) ; cytochrome CYP3A4;


【Funds】 Beijing Municipal Natural Science Foundation (7164291) National Major Scientific and Technological Special Project for “Major New Drugs Development” (2015ZX09501004-003-003) Special Scientific Research Fund of Chinese Medicine Industry (201507004)

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(Translated by WU XX)


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This Article


CN: 11-2272/R

Vol 42, No. 24, Pages 4827-4833

December 2017


Article Outline


  • 1 Materials and methods
  • 2 Results
  • 3 Discussion
  • References