6533b823fe1ef96bd127f811

RESEARCH PRODUCT

Inhibition of 5-lipoxygenase activity by the natural anti-inflammatory compound aethiopinone

M. Hernandez-perezR. BenrezzoukMaría Luisa FerrándizMaría Carmen TerencioMaría José AlcarazR. Rabanal

subject

Neutrophilsmedicine.drug_classImmunologyNitric Oxide Synthase Type IIPharmacologyLeukotriene B4DinoprostonePhospholipases AAnti-inflammatoryMicechemistry.chemical_compoundIn vivoAnimalsEdemaHumansMedicineLipoxygenase InhibitorsIC50InflammationPharmacologyArachidonic Acidbiologybusiness.industryAnti-Inflammatory Agents Non-SteroidalZymosanMembrane ProteinsEarbiology.organism_classificationIn vitroIsoenzymeschemistryCyclooxygenase 2Prostaglandin-Endoperoxide SynthasesArachidonate 5-lipoxygenaseImmunologyCyclooxygenase 1Macrophages PeritonealSalvia aethiopisbiology.proteinArachidonic acidNitric Oxide SynthasebusinessNaphthoquinones

description

Objetive and Design: We have investigated the mechanisms of action of aethiopinone, an anti-inflammatory compound from Salvia aethiopis L. roots.¶Material and Subjects: Human neutrophils from healthy volunteers and murine peritoneal macrophages. Swiss mice were randomly divided into groups of six animals.¶Treatment: Test compounds were applied topically in the mouse ear oedema test. In the air pouch, mice received aethiopinone (0.001-0.5 μmol/pouch or 12.5-50 mg/kg p.o.).¶Methods: LTB4 production was assayed in human neutrophils and COX-2 and iNOS activities in murine macrophages. Air pouches were induced subcutaneously in mice and injected with zymosan on the day six. Mouse ear oedema was induced by arachidonic acid. Dunnett's t-test was employed for statistical analysis.¶Results: We have observed potent inhibitory effects on human neutrophil LTB4 production without effects on COX or NOS activities. Aethiopinone is an in vitro inhibitor of 5-LO from human neutrophils (IC50 = 0.11 μM). In addition, aethiopinone reduced leukocyte accumulation and showed in vivo inhibitory activity on this enzyme.¶Conclusions: Our results indicate that inhibition of 5-LO could participate in the anti-inflammatory properties of this natural product.¶

https://doi.org/10.1007/s000110050730