RESUMO
The constitutive androstane receptor CAR is a xenosensing nuclear receptor that can be activated by natural polyphenols such as flavonoids and catechins. We examined alcoholic beverage phytochemicals for their ability to activate CAR. HepG2 cells were transfected with CAR expression vector and its reporter gene, and then treated with trans-resveratrol, ellagic acid, ß-caryophyllene, myrcene, and xanthohumol. A luciferase assay revealed that ellagic acid and trans-resveratrol activated both human and mouse CAR. Since CAR regulates many genes involved in energy metabolism, the possibility exists that these polyphenols would reduce the risk of certain alcohol-induced metabolic disorders with the help of CAR.
Assuntos
Consumo de Bebidas Alcoólicas/metabolismo , Bebidas Alcoólicas/análise , Metabolismo Energético/efeitos dos fármacos , Polifenóis/farmacologia , Receptores Citoplasmáticos e Nucleares/agonistas , Monoterpenos Acíclicos , Alcenos/farmacologia , Animais , Receptor Constitutivo de Androstano , Ácido Elágico/farmacologia , Flavonoides/farmacologia , Genes Reporter , Células Hep G2 , Humanos , Luciferases/análise , Camundongos , Monoterpenos/farmacologia , Plasmídeos , Sesquiterpenos Policíclicos , Propiofenonas/farmacologia , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Resveratrol , Comportamento de Redução do Risco , Sesquiterpenos/farmacologia , Estilbenos/farmacologia , TransfecçãoRESUMO
The constitutive androstane receptor (CAR) is known as a xeno-sensor that regulates genes involved in xenobiotic excretion and energy metabolism. This study tested a variety of polyphenols for their ability to modulate CAR activity. HepG2 cells were transfected with a CAR expression plasmid and a reporter plasmid containing the human CYP2B6 regulatory region and then treated with flavonoids, catechins, and other bioactive polyphenols. Luciferase assays revealed that baicalein (5,6,7-OH flavone) was a potent activator of both human and mouse CAR. Catechin gallates also activated human and mouse CAR. Wild-type and CAR knockout mice were treated with baicalein and chrysin (5,7-OH flavone), and their liver mRNA was analyzed by real-time polymerase chain reaction (PCR). A significant increase in cyp2b10 mRNA content was observed only in wild-type mice fed chrysin. These results suggest that dietary flavonoids regulate CAR activity and thereby accelerate both detoxification and energy metabolism.