Potent inhibition of human neutrophil activations by bractelactone, a novel chalcone from Fissistigma bracteolatum

Fissistigma bracteolatum is widely used in traditional medicine to treat inflammatory diseases. However, its active components and mechanisms of action remain unclear. In this study, (3Z)-6,7-dihydroxy-4-methoxy-3-(phenylmethylidene)-5-(3-phenylpropanoyl)-1-benzofuran-2(3H) (bractelactone), a novel chalcone from F. bracteolatum, showed potent inhibitory effects against superoxide anion (O2−) production, elastase release, and CD11b expression in formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP)-induced human neutrophils. However, bractelactone showed only weak inhibition of phorbol myristate acetate-caused O2− production. The peak cytosolic calcium concentration ([Ca2 +]i) was unaltered by bractelactone in FMLP-induced neutrophils, but the decay time of [Ca2 +]i was significantly shortened. In a calcium-free solution, changes in [Ca2 +]i caused by the addition of extracellular Ca2 + were inhibited by bractelactone in FMLP-activated cells. In addition, bractelactone did not alter the phosphorylation of p38 MAPK, ERK, JNK, or AKT or the concentration of cAMP. These results suggest that bractelactone selectively inhibits store-operated calcium entry (SOCE). In agreement with this concept, bractelactone suppressed sustained [Ca2 +]i changes in thapsigargin-activated neutrophils. Furthermore, bractelactone did not alter FMLP-induced formation of inositol 1,4,5-triphosphate. Taken together, our results demonstrate that the anti-inflammatory effects of bractelactone, an active ingredient of F. bracteolatum, in human neutrophils are through the selective inhibition of SOCE.

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► Bractelactone isolated from Fissistigma bracteolatum.
► Bractelactone inhibited FMLP-induced human neutrophil activations.
► Bractelactone had no effect on IP3 formation.
► Bractelactone did not alter MAPKs, AKT, and cAMP pathways.
► Bractelactone inhibited store-operated calcium entry.