Carnosic acid and carnosol potently inhibit human 5-lipoxygenase and suppress pro-inflammatory responses of stimulated human polymorphonuclear leukocytes

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• 作者：Daniel Poeckel ; Christine Greiner ; Moritz Verhoff ; Oliver Rau ; Lars Tausch ; Christina Hö ; rnig ; Dieter Steinhilber ; Manfred Schubert-Zsilavecz ; Oliver Werz
• 关键词：Carnosol ; Carnosic acid ; 5-Lipoxygenase ; Reactive oxygen species ; Leukocyte elastase ; Inflammation
• 刊名：Biochemical Pharmacology
• 出版年：2008
• 期刊代码：2_00062952
• 类别：pha
• 出版时间：1 July 2008
• 卷：76
• 期：1
• 页码：91-97
• 文件大小：463 K

摘要

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 (IC₅₀ = 15–20 μM [CA] and 7 μM [CS], respectively) as well as purified recombinant 5-lipoxygenase (EC number 1.13.11.34, IC₅₀ = 1 μM [CA] and 0.1 μM [CS], respectively), (II) both CA and CS potently antagonise intracellular Ca²⁺ 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.