Modulation of acute and chronic inflammatory processes by a traditional medicine preparation GCSB-5 both in vitro and in vivo animal models
Modulation of acute and chronic inflammatory processes by a traditional medicine preparation GCSB-5 both in vitro and in vivo animal models
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DOI：
10.1016/j.jep.2010.05.020
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发表时间：
2010-08-09
影响因子：
5.4
通讯作者：
Lee, Sang Kook
中科院分区：
文献类型：
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作者：
Chung, Hwa-Jin;Lee, Hak-Sun;Lee, Sang Kook
本研究目的：GCSB-5是一种由6种东方草药组成的中药制剂，在亚洲广泛用于炎症性疾病。在本研究中，我们证明了GCSB-5在体内和体外的抗炎作用及其潜在的作用机制。方法：采用动物急性和慢性炎症模型，研究GCSB-5的抗炎作用。为了进一步研究其抗炎作用的机制，我们还采用脂多糖（LPS）诱导的小鼠巨噬细胞RAW264.7细胞。结果：在体内动物模型中，口服GCSB-5可显著抑制TPA-和卡拉胶诱导的急性水肿和佐剂性关节炎。GCSB-5还能抑制血管通透性、白细胞迁移和肉芽肿形成。因此，GCSB-5通过下调诱导型一氧化氮合酶（iNOS） mRNA和蛋白的表达来抑制lps诱导的一氧化氮（NO）的产生。GCSB-5还抑制环氧化酶-2 （COX-2）和炎性细胞因子如白细胞介素-1 β和干扰素- β的表达。GCSB-5也能减轻LPS对NF-kappa B的激活，这与GCSB-5对IkB降解的抑制作用有关。激活Akt的信号通路也被GCSB-5减弱。结论：综上所述，我们的研究结果表明，GCSB-5可以减少急性和慢性炎症的发展，其抗炎特性可能部分是通过下调Akt信号通路和抑制NF-kappa B激活来抑制iNOS和COX-2的表达。这些发现提示GCSB-5可能是一种适用于炎症反应调节的传统治疗药物。2010爱思唯尔爱尔兰有限公司版权所有。
Aim of this study: GCSB-5 is a traditional medicine preparation composed with six oriental herbs which have been widely used for the inflammatory diseases in Asia. In the present study, we have demonstrated the anti-inflammatory effects of GCSB-5 in vivo and in vitro along with its underlying mechanism of action.Methods: The acute and chronic inflammation models in animals were applied to investigate the anti-inflammatory effects of GCSB-5. To further investigate the mechanism of the anti-inflammatory activity, lipopolysaccharide (LPS)-induced murine macrophage RAW264.7 cells were also employed.Results: In in vivo animal model, oral administration of GCSB-5 significantly inhibited TPA- and carrageenan-induced acute edema and adjuvant-induced arthritis. The vascular permeability, leukocyte migration, and granuloma formation were also inhibited by GCSB-5. In accordance, GCSB-5 suppressed the LPS-induced nitric oxide (NO) production by the downregulation of mRNA and protein expressions of inducible nitric oxide synthase (iNOS). GCSB-5 also suppressed the expressions of cyclooxygenase-2 (COX-2) and inflammatory cytokines such as interleukin-1 beta and interferon-beta. The activation of NF-kappa B by LPS was also alleviated by GCSB-5, which correlated with its inhibitory effect on IkB degradation. The signaling pathway with the activation of Akt was also attenuated by the treatment by GCSB-5.Conclusions: Taken together, our results demonstrate that GCSB-5 reduces the development of acute and chronic inflammation and its anti-inflammatory property might in part be a function of the inhibition of iNOS and COX-2 expression via down-regulation of the Akt signal pathway and inhibition of NF-kappa B activation. These findings suggest that GCSB-5 might be an applicable therapeutic traditional medicine in the regulation of the inflammatory response. (C) 2010 Elsevier Ireland Ltd. All rights reserved.