Inhibitory effects of bractelactone on superoxide anion and elastase release in human neutrophils

The Fissistigma bracteolatum Chatt., a climbing shrub, grows mainly in the southern part of China and Vietnam. As a folklore medicine, this plant is used to treat inflammation and enhance blood circulation.

Bractelactone, a novel chalcone derivative, was isolated from the stems of Fissistigma bracteolatum Chatt. In this study, a cellular model in isolated human neutrophils, which are important in the pathogenesis of rheumatoid arthritis, chronic obstructive pulmonary disease, and other inflammatory diseases, was established to elucidate the anti-inflammatory functions of bractelactone. Bractelactone inhibited formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP)-induced superoxide anion generation and elastase release in human neutrophils in a concentration-dependent manner with IC₅₀ values of 0.65±0.06 and 0.85±0.09µM, respectively. The inhibition of superoxide anion generation and elastase release by bractelactone was not reversed by the protein kinase A inhibitor. Consistent with this, it did not alter cAMP levels in human neutrophils. In addition, bractelactone did not alter fMLP-induced phosphorylation of MAPKs and Akt. Significantly, bractelactone concentration-dependently accelerated resequestration of cytosolic calcium in fMLP-activated human neutrophils. In summary, these results indicate that the suppressive effects of bractelactone on respiratory burst and degranulation of fMLP-induced human neutrophils are through the decrease of calcium mobilization, but not via the cAMP, Akt, and MAPKs signaling pathways.

Acknowledgements: This work was supported by grants from the Chang Gung Medical Research Foundation, Taiwan.