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 ³H-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.

PAF - calcium - pH - neutrophils - 14-deoxyandrographolide - MAPK - Andrographis paniculata - Acanthaceae

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