title: Potent inhibition of human neutrophil activations by bractelactone, a novel chalcone from Fissistigma bracteolatum.
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.
authors.affiliation: Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
authors.forename: Yang-Chang
authors.initials: YC
authors.lastname: Wu
authors.forename: Munisamy
authors.initials: M
authors.lastname: Sureshbabu
authors.forename: Yao-Ching
authors.initials: YC
authors.lastname: Fang
authors.forename: Yi-Hsiu
authors.initials: YH
authors.lastname: Wu
authors.forename: Yu-Hsuan
authors.initials: YH
authors.lastname: Lan
authors.forename: Fang-Rong
authors.initials: FR
authors.lastname: Chang
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Chang
authors.forename: Tsong-Long
authors.initials: TL
authors.lastname: Hwang
mesh_terms: D000328:Adult; D029061:Annonaceae / Q000737:chemistry*; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D039481:CD11b Antigen / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D047188:Chalcones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D015151:Immunoblotting; D020128:Inhibitory Concentration 50; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D010196:Pancreatic Elastase / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D018547:Plant Stems / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D039481:CD11b Antigen; D047188:Chalcones; C509295:ITGAM protein, human; D017382:Reactive Oxygen Species; D013481:Superoxides; D020928:Mitogen-Activated Protein Kinases; D010196:Pancreatic Elastase