Inhibition of Pro-Inflammatory Functions of Human Neutrophils by Constituents of Melodorum fruticosum Leaves

In an initial screening, the dichloromethane extract from the leaves of Melodorum fruticosum showed distinct inhibitory effects on the release of interleukin-8 (IL-8) in human neutrophils. Therefore, the aim of the present study was the phytochemical and pharmacological investigation of this extract, to better understand which compounds might be responsible for the anti-inflammatory effect. Phytochemical analysis led to the isolation of 12 known compounds and two new natural products, 5-hydroxy-6-(2-hydroxybenzyl)-4 ',7-dimethoxyflavanone (13) and 2 ',4 '-dihydroxy-3 '-(2-hydroxybenzyl)-4,6 '-dimethoxychalcone (14). The influence of the isolated compounds on the production and release of the pro-inflammatory factors IL-8, tumor necrosis factor alpha (TNF-alpha), reactive oxygen species (ROS), and adhesion molecules (CD62L and CD11b) in human neutrophils was evaluated. Three constituents, melodamide A, 2 ',4 '-dihydroxy-4,6 '-dimethoxychalcone, and 2 ',6 '-dihydroxy-4 '-methoxychalcone, showed significant inhibition of IL-8 release (IC50=6.6, 8.6, and 11.6 mu m, respectively) and TNF-alpha production (IC50=4.5, 13.3, and 6.2 mu m, respectively).