Inhibition of human sPLA(2) and 5-lipoxygenase activities by two neo-clerodane diterpenoids

The inhibitory effect of two neo-clerodane diterpenoids, E-isolinaridial (E I) and its methylketone derivative (EIM), isolated from Linaria saxatilis v ar. glutinosa on PLA(2) and other enzyme activities involved in the inflamm atory process was studied. Both compounds inhibited human synovial sPLA(2) in a concentration-dependent manner with IC50 values of 0.20 and 0.49 mu M, respectively, similar to scalaradial. Besides, these compounds decreased t he cell-free 5-lipoxygenase activity and A23187-induced neutrophil LTB4 bio synthesis. Another function of human neutrophils, such as receptor-mediated degranulation, was also significantly reduced. In contrast, none of the co mpounds affected superoxide generation in leukocytes, or cyclooxygenase-l, cyclooxygenase-2 and inducible nitric oxide synthase activities in cell-fre e assays. (C) 1999 Elsevier Science Inc.