Hederagenin, a major component of Clematis mandshurica Ruprecht root, attenuates inflammatory responses in RAW 264.7 cells and in mice

Hederagenin, a major component of Clematis mandshurica Ruprecht root, attenuates inflammatory responses in RAW 264.7 cells and in mice
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DOI:
10.1016/j.intimp.2015.10.002
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发表时间:
2015-12-01
影响因子:
5.6
通讯作者:
An, Won G.
An, Won G.
中科院分区:
医学2区
文献类型:
--
作者:
Lee, Chul Won;Park, Sang Mi;An, Won G.

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铁线莲根在亚洲被用作传统的抗炎、止痛和抗肿瘤药物。它的主要活性成分是一种天然存在的三萜--淫羊藿素,在本研究中,我们用酶联免疫吸附试验、Western印迹和RT-PCR法检测了淫羊藿素对内毒素刺激的RAW 264.7细胞的抗炎作用。此外,我们还用角叉菜胶诱导的小鼠足肿胀实验观察了其对体内急性炎症的影响。此外,还观察了角叉菜胶对小鼠后爪皮肤组织病理学和组织形态计量学的影响。Hederagenin(10,30和100 mU M)可抑制脂多糖刺激的iNOS、COX-2和NF-kappaB的蛋白表达以及内毒素诱导的NO、PGE(2)、TNE-α、IL-1β和IL-6的产生。与这些结果一致的是,Hederagenin还呈剂量依赖性地降低内毒素诱导的iNOS和COX-2以及上述细胞因子的mRNA水平。有趣的是,角叉菜胶诱导的小鼠后足肿胀实验结果显示,常春藤多酚具有抗肿胀作用。此外,Hederagenin(30 mg/kg)可抑制角叉菜胶引起的皮肤增厚、炎细胞浸润和肥大细胞脱颗粒。这些结果提示,长春花素可能具有抗炎作用。(C)2015爱思唯尔B.V.保留所有权利。
Clematis mandshurica Ruprecht root has been used in Asia as a traditional anti-inflammatory, analgesic, and antitumor agent. Its main active component is hederagenin, a naturally occurring triterpene, and in this study, we examined the anti-inflammatory effects of hederagenin in lipopolysaccharide-stimulated RAW 264.7 cells using an enzyme-linked immunosorbent assay, Western blot, and RT-PCR In addition, its effects on acute inflammation in vivo were observed using a carrageenan-induced mouse hind paw edema assay. Furthermore, the changes on the histopathology and histomorphometry of hind paw skins were examined using carrageenan-treated mice. Treatment with hederagenin (10,30 and 100 mu M) resulted in inhibited levels of protein expression of lipopolysaccharide-stimulated iNOS, COX-2, and NF-kappa B as well as production of NO, PGE(2), TNE-alpha, IL-1 beta, and IL-6 induced by lipopolysaccharide. Consistent with these results, hederagenin also dose-dependently reduced the lipopolysaccharide-induced mRNA levels of iNOS and COX-2, and of the above-mentioned cytokines. Interestingly, results of the carrageenan-induced mouse hind paw edema assay showed an anti-edema effect of hederagenin. Furthermore, hederagenin (30 mg/kg) inhibited the carrageenan-induced increases in skin thicknesses, infiltrated inflammatory cells, and mast cell degranulation. These results suggest that hederagenin may possess anti-inflammatory activities. (C) 2015 Elsevier B.V. All rights reserved.