期刊
TOXICOLOGY AND APPLIED PHARMACOLOGY
卷 266, 期 3, 页码 399-407出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2012.11.021
关键词
Bractelactone; Calcium; Elastase; Fissistigma bracteolatum; Neutrophils; Superoxide anion
资金
- Chang Gung University [EMRPD1A0881, CMRPD160211-2, CMRPD180221-3]
- National Science Council, Taiwan [NSC 99-2320-B-182-006-MY3]
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 (O-2(center dot-)) 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 O-2(center dot-) 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. (C) 2012 Elsevier Inc. All rights reserved.
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