Inhibitory effects of kaurenoic acid from Aralia continentalis on LPS-induced inflammatory response in RAW264.7 macrophages
Inhibitory effects of kaurenoic acid from Aralia continentalis on LPS-induced inflammatory response in RAW264.7 macrophages
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DOI：
10.1016/j.phymed.2010.11.010
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发表时间：
2011-06-15
期刊：
影响因子：
7.9
通讯作者：
Kim, Yeong Shik
中科院分区：
文献类型：
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作者：
Choi, Ran Joo;Shin, Eun Myoung;Kim, Yeong Shik
本研究研究了从大陆楤木（aralialcontinentalis, Araliaceae）的根中分离的二萜类化合物香豆烯酸的抗炎作用。为研究其抗炎作用，采用不同浓度的丁香烯酸处理lps诱导的RAW264.7巨噬细胞，并建立卡拉胶诱导的足跖水肿小鼠体内模型。kaurenic acid （ent- karenic -16-en-19-oic acid）对lps诱导的RAW264.7巨噬细胞一氧化氮（NO）的产生、前列腺素E(2) （PGE(2)）的释放、环氧化酶-2 （COX-2）和诱导型一氧化氮合酶（iNOS）的表达具有剂量依赖性，对NO的产生和PGE(2)的释放的IC(50)（最大抑制浓度的一半）分别为51.73 (+/- 2.42)mu和106.09 (+/- 0.27)mu。电泳迁移率转移实验（EMSA）显示，丁香烯酸还能剂量依赖性地抑制lps诱导的NF-kappa B的激活，并且在100 μ m时几乎消除NF-kappa B DNA结合亲和力。此外，在卡拉胶诱导的足跖水肿模型中，研究了丁香烯酸的体内抗炎作用。与对照组比较，每组8只ICR小鼠注射卡拉胶，每小时观察一次。在诱导后5小时，钙烯酸剂量依赖性地减少足跖肿胀达34.4%，在急性炎症模型中显示出抑制作用。综上所述，我们的数据表明，香豆烯酸是一种主要的二萜类物质，它具有抗炎活性，抑制iNOS和COX-2的表达可能是其抗炎作用的机制之一。(C) 2010 Elsevier GmbH版权所有。
This study investigates the anti-inflammatory effects of a diterpenoid, kaurenoic acid, isolated from the root of Aralia continentalis (Araliaceae). To determine its anti-inflammatory effects, LPS-induced RAW264.7 macrophages were treated with different concentrations of kaurenoic acid and carrageenan-induced paw edema mice model was used in vivo. Kaurenoic acid (ent-kaur-16-en-19-oic acid) dose-dependently inhibited nitric oxide (NO) production, prostaglandin E(2) (PGE(2)) release, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression at micromolar concentrations in LPS-induced RAW264.7 macrophages with IC(50) (the half maximal inhibitory concentration) values of 51.73 (+/- 2.42) mu M and 106.09 (+/- 0.27) mu M in NO production and PGE(2) release, respectively. Kaurenoic acid also dose-dependently inhibited LPS-induced activation of NF-kappa B as assayed by electrophorectic mobility shift assay (EMSA) and it almost abolished NF-kappa B DNA binding affinity at 100 mu M. Furthermore, the in vivo anti-inflammatory effect of kaurenoic acid was examined in a carrageenan-induced paw edema model. Eight ICR mice in each group were injected with carrageenan and observed hourly, compared with the control group. Kaurenoic acid dose-dependently reduced paw swelling up to 34.4% at 5 h after induction, demonstrating inhibition in an acute inflammation model. Taken together, our data suggest that kaurenoic acid, a major diterpenoid from the root of A. continentalis shows anti-inflammatory activity and the inhibition of iNOS and COX-2 expression might be one of the mechanisms responsible for its anti-inflammatory properties. (C) 2010 Elsevier GmbH. All rights reserved.