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.
- Fissistigma bracteolatum
- Superoxide anion
ASJC Scopus subject areas
Wu, Y. C., Sureshbabu, M., Fang, Y. C., Wu, Y. H., Lan, Y. H., Chang, F. R., Chang, Y. W., & Hwang, T. L. (2013). Potent inhibition of human neutrophil activations by bractelactone, A novel chalcone from Fissistigma bracteolatum. Toxicology and Applied Pharmacology, 266(3), 399-407. https://doi.org/10.1016/j.taap.2012.11.021