6533b831fe1ef96bd1299935

RESEARCH PRODUCT

Inhibition of human sPLA2 and 5-lipoxygenase activities by two neo-clerodane diterpenoids

J. M. Miguel Del CorralMaría Luisa FerrándizMaría Carmen TerencioA. San FelicianoM. L. De La PuenteMarina GordalizaM. J. AlcarazR. Benrezzouk

subject

NeutrophilsBiologyLeukotriene B4Phospholipases AGeneral Biochemistry Genetics and Molecular Biologychemistry.chemical_compoundBiosynthesisHumansLipoxygenase InhibitorsEnzyme InhibitorsGeneral Pharmacology Toxicology and Pharmaceuticschemistry.chemical_classificationSuperoxideElastaseDegranulationGeneral MedicineNitric oxide synthasePhospholipases A2EnzymechemistryBiochemistryArachidonate 5-lipoxygenasebiology.proteinNeutrophil degranulationDiterpenesLeukocyte Elastase

description

Abstract 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 sPLA 2 in a concentration-dependent manner with IC 50 values of 0.20 and 0.49 μM, respectively, similar to scalaradial. Besides, these compounds decreased the cell-free 5-lipoxygenase activity and A23187-induced neutrophil LTB 4 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.

yearjournalcountryeditionlanguage
1999-06-03Life Sciences
https://doi.org/10.1016/s0024-3205(99)00119-8