title: PXR Mediated Protection against Liver Inflammation by Ginkgolide A in Tetrachloromethane Treated Mice.
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 CCl4-induced mouse hepatitis. siRNA-mediated decrease of PXR expression significantly reduced the efficacy of Ginkgolide A in treating CCl4-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 IκBα through binding of IκBα. Inhibition of NF-κB activity by NF-κB-specific suppressor IκBα is one of the potential mechanisms of Ginkgolide A against CCl4-induced liver inflammation.
authors.affiliation: Institute of Pharmaceutical Biotechnology and Engineering, College of Biological Science and Biotechnology, Fuzhou University, Fuzhou, Fujian, 350108, China.
authors.forename: Nanhui
authors.initials: N
authors.lastname: Ye
authors.affiliation: Institute of Pharmaceutical Biotechnology and Engineering, College of Biological Science and Biotechnology, Fuzhou University, Fuzhou, Fujian, 350108, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Pharmaceutical Biotechnology and Engineering, College of Biological Science and Biotechnology, Fuzhou University, Fuzhou, Fujian, 350108, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Hong
authors.affiliation: Institute of Pharmaceutical Biotechnology and Engineering, College of Biological Science and Biotechnology, Fuzhou University, Fuzhou, Fujian, 350108, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Institute of Pharmaceutical Biotechnology and Engineering, College of Biological Science and Biotechnology, Fuzhou University, Fuzhou, Fujian, 350108, China.
authors.forename: Chaotong
authors.initials: C
authors.lastname: Lin
authors.affiliation: Institute of Pharmaceutical Biotechnology and Engineering, College of Biological Science and Biotechnology, Fuzhou University, Fuzhou, Fujian, 350108, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Meng
keywords: Ginkgolide A; IκBα expression; Liver inflammation; PXR knock-down; Pregnane X receptor