Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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PXR Mediated Protection against Liver Inflammation by Ginkgolide A in Tetrachloromethane Treated Mice

  • Ye, Nanhui (Institute of Pharmaceutical Biotechnology and Engineering, College of Biological Science and Biotechnology, Fuzhou University) ;
  • Wang, Hang (Institute of Pharmaceutical Biotechnology and Engineering, College of Biological Science and Biotechnology, Fuzhou University) ;
  • Hong, Jing (Institute of Pharmaceutical Biotechnology and Engineering, College of Biological Science and Biotechnology, Fuzhou University) ;
  • Zhang, Tao (Institute of Pharmaceutical Biotechnology and Engineering, College of Biological Science and Biotechnology, Fuzhou University) ;
  • Lin, Chaotong (Institute of Pharmaceutical Biotechnology and Engineering, College of Biological Science and Biotechnology, Fuzhou University) ;
  • Meng, Chun (Institute of Pharmaceutical Biotechnology and Engineering, College of Biological Science and Biotechnology, Fuzhou University)
  • Received : 2015.06.11
  • Accepted : 2015.10.02
  • Published : 2016.01.01
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Abstract

The pregnane X receptor (PXR), a liver and intestine specific receptor,, has been reported to be related with the repression of inflammation as well as activation of cytochromosome P450 3A (CYP3A) expression. We examined the effect of PXR on tetrachloromethane (CCl4)-induced mouse liver inflammation in this work. Ginkgolide A, one main component of Ginkgo biloba extracts (GBE), activated PXR and enhanced PXR expression level, displayed both significant therapeutic effect and preventive effect against $CCl_4$-induced mouse hepatitis. siRNA-mediated decrease of PXR expression significantly reduced the efficacy of Ginkgolide A in treating $CCl_4$-induced inflammation in mice. Flavonoids, another important components of GBE, were shown anti-inflammatory effect in a different way from Ginkgolide A which might be independent on PXR because flavonoids significantly inhibited CYP3A11 activities in mice. The results indicated that anti-inflammatory effect of PXR might be mediated by enhancing transcription level of $I{\kappa}B{\alpha}$ through binding of $I{\kappa}B{\alpha}$. Inhibition of NF-${\kappa}B$ activity by NF-${\kappa}B$-specific suppressor $I{\kappa}B{\alpha}$ is one of the potential mechanisms of Ginkgolide A against CCl4-induced liver inflammation.

Keywords

References

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