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作者:

Zhang Zhao-Yan (Zhang Zhao-Yan.) | Wang Yu-Guang (Wang Yu-Guang.) | Huang Xiao-Yan (Huang Xiao-Yan.) | Wang Mei-Xi (Wang Mei-Xi.) | Yang Liang (Yang Liang.) | Ma Zeng-Chun (Ma Zeng-Chun.) | Tang Xiang-Lin (Tang Xiang-Lin.) | Gao Yue (Gao Yue.)

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摘要:

This paper aimed to study the six chemical components of Polygoni Multiflori Radix (gallic acid, quercetin, luteolin, kaempferol, resveratrol, apigenin). By the established pregnane X receptor (human pregnant X receptor, PXR) CYP3A4 mediated drug induced rapid screening technique, the effect of chemical components on the cell activity was detected by MTS cell method, and the value of IC₅₀ was calculated. The dual luciferase reporter system was used to co-transfect PXR reporter gene expression vector containing transcriptional regulation and CYP3A4 with HepG2 cells, with 10 μmol·L⁻¹ rifampicin (RIF) as a positive control, and 10 μmol·L⁻¹ of ketoconazole (TKZ) as negative control. Gallic acid, quercetin, luteolin, kaempferol, apigenin, resveratrol(5, 10, 20 μmol·L⁻¹) were used to incubate for 24 h, and the luciferase activity was detected. The results showed that when plasmid pcDNA3.1 was co-transfected with pGL4.17-CYP3A4, gallic acid and resveratrol had an inhibitory effect on the regulation of CYP3A4, and quercetin, luteolin, kaempferol had an inductive effect on CYP3A4; when pcDNA3.14-PXR was co-transfected with pGL4.17-CYP3A4, quercetin, luteolin, kaempferol, apigenin, resveratrol had an inductive effect. To sum up, the 6 reported liver injury components had inhibitory or activating effects on CYP3A4. After PXR plasmid was involved, 5 components had an inductive effect on CYP3A4, and the inductive effects of 2 components were significantly different. In this experiment, we found that 2 kinds of potential liver injury components in Polygoni Multiflori Radix had been induced by CYP3A4, which was achieved through PXR regulation. It suggested that attention shall be paid to potential drug interactions when combined with Polygoni Multiflori Radix, so as to improve the safety and efficacy.

关键词:

Polygoni Multiflori Radix human pregnane X receptor(PXR) safety of traditional Chinese medicine components of liver injury CYP3A4

作者机构:

  • [ 1 ] [Zhang Zhao-Yan]College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China
  • [ 2 ] [Wang Yu-Guang]Department of Pharmaceutical Sciences, Beijing Institution of Radiation Medicine, Beijing 100850, China
  • [ 3 ] [Huang Xiao-Yan]Department of Pharmaceutical Sciences, Beijing Institution of Radiation Medicine, Beijing 100850, China
  • [ 4 ] [Wang Mei-Xi]Department of Pharmaceutical Sciences, Beijing Institution of Radiation Medicine, Beijing 100850, China
  • [ 5 ] [Yang Liang]Department of Pharmaceutical Sciences, Beijing Institution of Radiation Medicine, Beijing 100850, China
  • [ 6 ] [Ma Zeng-Chun]Department of Pharmaceutical Sciences, Beijing Institution of Radiation Medicine, Beijing 100850, China
  • [ 7 ] [Tang Xiang-Lin]Department of Pharmaceutical Sciences, Beijing Institution of Radiation Medicine, Beijing 100850, China
  • [ 8 ] [Gao Yue]College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China

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来源 :

China journal of Chinese materia medica

ISSN: 1001-5302

年份: 2018

期: 20

卷: 43

页码: 4104-4110

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