Investigation of the inhibitory effect of broussochalcone A on respiratory burst in neutrophils.
Broussochalcone A, a prenylated chalcone isolated from Broussonetia papyrifera (L.) VENT. (Moraceae), inhibited O2 consumption in formylmethionyl-leucyl-phenylalanine (fMLP)- and phorbol 12-myristate 13-acetate (PMA)-stimulated rat neutrophils in a concentration-dependent manner with IC50 values of 70.3 +/- 4.9 and 63.9 +/- 7.1 microM, respectively. Broussochalcone A did not affect the fMLP-induced increase of cellular inositol trisphosphate (IP3) and [Ca2+]i. However, the enzyme activity of neutrophil cytosolic protein kinase C was effectively suppressed by broussochalcone A. Broussochalcone A had no effect on either [3H]phorbol 12,13-dibutyrate ([3H]PDB) binding to neutrophil cytosolic protein kinase C or on PMA-induced membrane translocation of protein kinase C-beta in neutrophils. Broussochalcone A suppressed the enzyme activity of trypsin-treated rat brain protein kinase C in a concentration-dependent manner. In PMA-activated neutrophil particulate NADPH oxidase, broussochalcone A attenuated superoxide anion radical (O2.-) generation with an IC50 value of 61.8 +/- 5.4 microM. These results show that the inhibitory effect of broussochalcone A on respiratory burst in neutrophils is not mediated by the reduction of phospholipase C activity, but is mediated partly by the suppression of protein kinase C activity through interference with the catalytic region and by the attenuation of O2.- generation from the NADPH oxidase complex.
Wang
J P
JP
Department of Medical Research, Taichung Veterans General Hospital, Taiwan.
Tsao
L T
LT
Raung
S L
SL
Lin
C N
CN
D000818:Animals; D002118:Calcium / Q000097:blood; D002462:Cell Membrane / Q000201:enzymology; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology; D047188:Chalcones; D007295:Inositol Phosphates / Q000097:blood; D007527:Isoenzymes / Q000097:blood / Q000187:drug effects; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D019255:NADPH Oxidases / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D011493:Protein Kinase C / Q000097:blood / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012118:Resorcinols / Q000494:pharmacology*; D016897:Respiratory Burst / Q000187:drug effects*; D014357:Trypsin / Q000494:pharmacology
D047188:Chalcones; D007295:Inositol Phosphates; D007527:Isoenzymes; D012118:Resorcinols; D015240:Phorbol 12,13-Dibutyrate; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002599:Chalcone; C106525:broussochalcone A; D019255:NADPH Oxidases; D011493:Protein Kinase C; D014357:Trypsin; D002118:Calcium