Carnosic acid and carnosol potently inhibit human 5-lipoxygenase and suppress pro-inflammatory responses of stimulated human polymorphonuclear leukocytes
Carnosic acid and carnosol potently inhibit human 5-lipoxygenase and suppress pro-inflammatory responses of stimulated human polymorphonuclear leukocytes
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DOI：
10.1016/j.bcp.2008.04.013
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发表时间：
2008-07-01
影响因子：
5.8
通讯作者：
Werz, Oliver
中科院分区：
文献类型：
--
作者：
Poeckel, Daniel;Greiner, Christine;Werz, Oliver
鼠尾草酸(CA)和鼠尾草醇(CS)是存在于迷迭香(Rosemary)和鼠尾草(Sage)等唇形草本植物中的酚类二萜化合物。这些植物的提取物显示出抗炎特性，但其潜在的机制在很大程度上尚不清楚。最近，我们发现CA和CS激活了过氧化物酶体增殖物激活受体γ，在基因调控水平上具有抗炎作用。在这里，我们讨论了CA和CS对人多形核白细胞(PMNL)典型功能的短期影响。结果发现：(1)CA和CS均能抑制完整PMNL(IC50分别为15-20 mU M[CA]和7 mU M[CS])和纯化的重组5-脂氧合酶(EC编号为1.13.11.34，IC50分别为1 mU M[CA]和0.1 mU M[CS])中促炎症白三烯的形成；(2)CA和CS均能有效地拮抗细胞内钙离子的动员。(Iii)CA和CS可抑制活性氧的形成和人白细胞弹性蛋白酶的分泌(EC编号3.4.21.37)。综上所述，我们的发现为所报道的含有CS和CA的提取物的抗炎特性提供了药理学基础。(C)2008 Elsevier Inc.保留所有权利。
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 proinflammatory leukotrienes in intact PMNL (IC50 = 15-20 mu M [CA] and 7 mu M [CS], respectively) as well as purified recombinant 5-lipoxygenase (EC number 1.13.11.34, IC50 = 1 mu M [CA] and 0.1 mu M [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. (c) 2008 Elsevier Inc. All rights reserved.