Carnosic acid and carnosol potently inhibit human 5-lipoxygenase and suppress pro-inflammatory responses of stimulated human polymorphonuclear leukocytes.
Carnosic acid (CA) and carnosol (CS) are phenolic diterpenes present in several labiate herbs like Rosmarinus officinalis (Rosemary) and Salvia officinalis (Sage). Extracts of these plants exhibit anti-inflammatory properties, but the underlying mechanisms are largely undefined. Recently, we found that CA and CS activate the peroxisome proliferator-activated receptor gamma, implying an anti-inflammatory potential on the level of gene regulation. Here we address short-term effects of CA and CS on typical functions of human polymorphonuclear leukocytes (PMNL). We found that (I), CA and CS inhibit the formation of pro-inflammatory leukotrienes in intact PMNL (IC(50)=15-20 microM [CA] and 7 microM [CS], respectively) as well as purified recombinant 5-lipoxygenase (EC number 1.13.11.34, IC(50)=1 microM [CA] and 0.1 microM [CS], respectively), (II) both CA and CS potently antagonise intracellular Ca(2+) mobilisation induced by a chemotactic stimulus, and (III) CA and CS attenuate formation of reactive oxygen species and the secretion of human leukocyte elastase (EC number 3.4.21.37). Together, our findings provide a pharmacological basis for the anti-inflammatory properties reported for CS- and CA-containing extracts.
Poeckel
Daniel
D
Department of Pharmaceutical Analytics, Pharmaceutical Institute, Eberhard-Karls-University Tübingen, Auf der Morgenstelle 8, D-72076 Tübingen, Germany.
Greiner
Christine
C
Verhoff
Moritz
M
Rau
Oliver
O
Tausch
Lars
L
Hörnig
Christina
C
Steinhilber
Dieter
D
Schubert-Zsilavecz
Manfred
M
Werz
Oliver
O
D045784:Abietanes / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D045784:Abietanes; D016859:Lipoxygenase Inhibitors; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C068623:carnosol; C018381:salvin; D002118:Calcium