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

Yang Chang Wu, Munisamy Sureshbabu, Yao Ching Fang, Yi Hsiu Wu, Yu Hsuan Lan, Fang Rong Chang, Ya Wen Chang, Tsong Long Hwang

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)399-407
Number of pages9
JournalToxicology and Applied Pharmacology
Volume266
Issue number3
DOIs
Publication statusPublished - Feb 1 2013
Externally publishedYes

Keywords

  • Bractelactone
  • Calcium
  • Elastase
  • Fissistigma bracteolatum
  • Neutrophils
  • Superoxide anion

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

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