14-deoxyandrographolide as a platelet activating factor antagonist in bovine neutrophils

Abstract 14-Deoxyandrographolide (14-DAP) is a labdane diterpene isolated from ANDROGRAPHIS PANICULATA with previously reported calcium channel blocking activity. Its potential platelet activating factor (PAF) antagonistic activity in bovine neutrophils was assessed. 14-DAP, in concentrations between 10 - 100 μM, reduced the extracellular acidification rate and the intracellular alkalinization in a dose-dependent manner. In addition, 14-DAP reduced PAF-induced calcium flux in the presence of extracellular calcium, and tyrosine phosphorylation of a 44 kDa protein corresponding to the MAPK ERK1 . However, 14-DAP reduced the 3 H-PAF binding with a K i of 7.8 × 10 - 9 M, and a Hill slope of 0.63, suggesting that there is more than one binding site for 14-DAP. We concluded that 14-DAP is an effective antagonist of PAF-mediated processes in bovine neutrophils, probably by virtue of its calcium channel blocking property.