RESUMO
The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcriptional factor belonging to the basic helix-loop-helix-Per-Ahr/Arnt-Sim family. In this study, we evaluated the AhR agonistic activities of 12 xanthones isolated from the roots of M. cochinchinensis var. gerontogea using HepG2 cells transfected with pX4TK-Luc reporter plasmids. Gerontoxanthone B (GXB) showed the most potent activity at a concentration of 10µM, and the activity was inhibited by AhR antagonists such as GNF-351. GXB also increased cytochrome P450 1A1 mRNA and protein levels in HepG2 cells. Similar to the AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin, however, GXB suppressed the IL-1ß-induced mRNA level of SAA1, an acute-phase response gene that is up-regulated AhR-dependently but XRE-independently. Thus, GXB shows XRE-dependent transcriptional activity and XRE-independent activity involving AhR.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Maclura/química , Receptores de Hidrocarboneto Arílico/agonistas , Xantonas/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Relação Dose-Resposta a Droga , Células Hep G2 , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Células Tumorais Cultivadas , Xantonas/química , Xantonas/isolamento & purificaçãoRESUMO
A new xanthone (1) and a new naturally occurring xanthone (2) were isolated from the roots of Maclura cochinchinensis (Lour.) Corner var. gerontogea (Sieb. et Zucc.) Ohashi together with 10 known xanthones (3-12). Their structures were established by spectroscopic analyses including 1D and 2D NMR. Their retinoic acid receptor-α agonistic activity was evaluated using a luciferase reporter assay. Compound 2, gerontoxanthone A (3), gerontoxanthone B (4), and cudraxanthone I (11) showed moderate concentration-dependent activity. Furthermore, these four xanthones synergistically increased transcriptional activity in this assay in the presence of bexarotene, an RXR agonist.
