Inhibition of 5-lipoxygenase activity by the natural anti-inflammatory compound aethiopinone.
OBJECTIVE
We have investigated the mechanisms of action of aethiopinone, an anti-inflammatory compound from Salvia aethiopis L. roots.


METHODS
Human neutrophils from healthy volunteers and murine peritoneal macrophages. Swiss mice were randomly divided into groups of six animals.


METHODS
Test compounds were applied topically in the mouse ear oedema test. In the air pouch, mice received aethiopinone (0.001-0.5 pmol/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 microM). 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.
Benrezzouk
R
R
Department of Pharmacology, University of Valencia, Faculty of Pharmacy, Spain.
Terencio
M C
MC
Ferrandiz
M L
ML
Hernandez-Perez
M
M
Rabanal
R
R
Alcaraz
M J
MJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D016718:Arachidonic Acid; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D004423:Ear; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D007975:Leukotriene B4 / Q000096:biosynthesis; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000201:enzymology; D008565:Membrane Proteins; D051379:Mice; D009285:Naphthoquinones / Q000494:pharmacology* / Q000627:therapeutic use; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007527:Isoenzymes; D016859:Lipoxygenase Inhibitors; D008565:Membrane Proteins; D009285:Naphthoquinones; D007975:Leukotriene B4; D016718:Arachidonic Acid; C101972:aethiopinone; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D010741:Phospholipases A; D015232:Dinoprostone