RESUMO
A new naphthalene glycoside was isolated from the leaves and stems of Chimaphila umbellata Barton. Its chemical structure was elucidated to be 2,7-dimethyl-1,4-dihydroxynaphthalene-1-O-ß-D-glucopyranoside (DMDHNG), based on spectroscopic evidence. DMDHNG significantly inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-induced tartrate-resistant acid phosphatase (TRAP) activity and the formation of multinucleated osteoclasts in a dose-dependent manner. In addition, the new glycoside inhibited the RANKL-induced mRNA expression of osteoclast-associated genes that encode TRAP, cathepsin K, and another transcription factor-nuclear factor of activated T-cells c1. We believe that the inhibitory effects of DMDHNG on the osteoclast differentiation may be exploited for a therapeutic benefit.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Glucosídeos/farmacologia , Naftóis/farmacologia , Osteoclastos/efeitos dos fármacos , Pyrolaceae/química , Fosfatase Ácida/genética , Fosfatase Ácida/metabolismo , Catepsina K/genética , Relação Dose-Resposta a Droga , Glucosídeos/administração & dosagem , Glucosídeos/isolamento & purificação , Isoenzimas/genética , Isoenzimas/metabolismo , Fatores de Transcrição NFATC/genética , Naftóis/administração & dosagem , Naftóis/isolamento & purificação , Osteoclastos/citologia , Folhas de Planta , Caules de Planta , Ligante RANK/administração & dosagem , RNA Mensageiro/metabolismo , Fosfatase Ácida Resistente a TartaratoRESUMO
Bioassay-guided fractionation of Chimaphila umbellata (L.) W. Bart (Pyrolaceae) ethanol extracts led to the identification of 2,7-dimethyl-1,4-naphthoquinone (chimaphilin) as the principal antifungal component. The structure of chimaphilin was confirmed by 1H and 13C NMR spectroscopy. The antifungal activity of chimaphilin was evaluated using the microdilution method with Saccharomyces cerevisiae (0.05mg/mL) and the dandruff-associated fungi Malassezia globosa (0.39mg/mL) and Malassezia restricta (0.55mg/mL). Pronounced antioxidant activity of C. umbellata crude extract was also identified using the DPPH (2,2-diphenyl-1-picrylhydrazyl) assay, suggesting this phytomedicine has an antioxidant function in wound healing. A chemical-genetic profile was completed with chimaphilin using approximately 4700 S. cerevisiae gene deletion mutants. Cellular roles of deleted genes in the most susceptible mutants and secondary assays indicate that the targets for chimaphilin include pathways involved in cell wall biogenesis and transcription.
