Inhibition of human sPLA2 and 5-lipoxygenase activities by two neo-clerodane diterpenoids.
The inhibitory effect of two neo-clerodane diterpenoids, E-isolinaridial (EI) and its methylketone derivative (EIM), isolated from Linaria saxatilis var. glutinosa, on PLA2 and other enzyme activities involved in the inflammatory process was studied. Both compounds inhibited human synovial sPLA2 in a concentration-dependent manner with IC50 values of 0.20 and 0.49 microM, respectively, similar to scalaradial. Besides, these compounds decreased the cell-free 5-lipoxygenase activity and A23187-induced neutrophil LTB4 biosynthesis. Another function of human neutrophils, such as receptor-mediated degranulation, was also significantly reduced. In contrast, none of the compounds affected superoxide generation in leukocytes, or cyclooxygenase-1, cyclooxygenase-2 and inducible nitric oxide synthase activities in cell-free assays.
Benrezzouk
R
R
Department of Pharmacology, University of Valencia, Spain.
Terencio
M C
MC
Ferrándiz
M L
ML
San Feliciano
A
A
Gordaliza
M
M
Miguel del Corral
J M
JM
de la Puente
M L
ML
Alcaraz
M J
MJ
D004224:Diterpenes / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism; D007975:Leukotriene B4 / Q000096:biosynthesis; D016859:Lipoxygenase Inhibitors; D009504:Neutrophils / Q000378:metabolism; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2
D004224:Diterpenes; D004791:Enzyme Inhibitors; D016859:Lipoxygenase Inhibitors; D007975:Leukotriene B4; D010741:Phospholipases A; D054467:Phospholipases A2; D019272:Leukocyte Elastase