natsudaidain and nobiletin

Flavonoids inhibit the activity of chemical mediators released from mast cells. Our aim was to investigate the effects of natsudaidain, a polymethoxyflavone isolated from Citrus plants, on mast cells.. We investigated the inhibitory effects of natsudaidain, which is a polymethoxyflavone isolated from Citrus plants, on histamine release, tumour necrosis factor-alpha production and cyclooxygenase-2 expression in Ca ionophore-stimulated rat basophilic leukemia cells (A23187-stimulated RBL-2H3 cells) by spectrofluorometric, ELISA and immunoblotting methods.. The percent of histamine release from A23187-stimulated RBL-2H3 cells pretreated with natsudaidain at 5, 25 and 50 microM was not changed as compared with non-treated A23187-stimulated cells. At 100 and 200 microM, natsudaidain pretreatment resulted in slightly reduced histamine release (% histamine release, 89.8+/-3.5% and 71.5+/-5.6% at 100 and 200 microM). Thus, natsudaidain hardly affects histamine release from RBL-2H3 cells, except at high concentrations. On the other hand, natsudaidain dose-dependently inhibited tumour necrosis factor-alpha protein and mRNA levels in A23187-stimulated RBL-2H3 cells; a concentration of 6.8 microM was required for a 50% reduction. In addition, all concentrations of this compound that we tested also inhibited cyclooxygenase-2 protein expression. The mRNA levels of cyclooxygenase-2 in A23187-stimulated RBL-2H3 cells treated with natsudaidain were also markedly decreased. The phosphorylated-p38 MAPK protein levels in A23187-stimulated RBL-2H3 cells treated with natsudaidain were lower than in the non-treated cells.. These findings suggest that natsudaidain inhibits tumour necrosis factor-alpha and cyclooxygenase-2 production by suppressing p38 MAPK phosphorylation but not p65 NFkappaB phosphorylation, and that natsudaidain might alleviate inflammatory diseases.

Topics: Analysis of Variance; Animals; Calcimycin; Cell Line, Tumor; Chromatography, High Pressure Liquid; Citrus; Cyclooxygenase 2; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Flavones; Flavonoids; Histamine Release; Immunoblotting; Ionophores; Molecular Structure; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Plant Leaves; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Time Factors; Tumor Necrosis Factor-alpha

Four compounds were isolated from the pericarp of Citrus reticulata and three of them were identified as natsudaidai, nobiletin and 3,5,6,7,8,3',4'-heptamethoxyflavone. Natsudaidai and 3,5,6,7,8,3',4'-heptamethoxyflavone were obtained from this plant for the first time.

Topics: Citrus; Flavones; Flavonoids; Magnetic Resonance Spectroscopy; Spectrophotometry, Ultraviolet