PXR Mediated Protection against Liver Inflammation by Ginkgolide A in Tetrachloromethane Treated Mice
| Autor: | Chun Meng, Chaotong Lin, Tao Zhang, Hong Jing, Hang Wang, Nanhui Ye |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
CYP3A CCL4 Inflammation Pharmacology digestive system Biochemistry Liver inflammation IκBα expression 03 medical and health sciences chemistry.chemical_compound Drug Discovery medicine Receptor Pregnane X receptor biology Ginkgo biloba Chemistry biology.organism_classification digestive system diseases IκBα 030104 developmental biology Ginkgolide A PXR knock-down Ginkgolide Molecular Medicine Original Article medicine.symptom |
| Zdroj: | Biomolecules & Therapeutics |
| ISSN: | 1976-9148 2005-4483 |
| DOI: | 10.4062/biomolther.2015.077 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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