Chikusetsusaponin V inhibits inflammatory responses via NF-κB and MAPK signaling pathways in LPS-induced RAW 264.7 macrophages

Chikusetsusaponin V inhibits inflammatory responses via NF-κB and MAPK signaling pathways in LPS-induced RAW 264.7 macrophages
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DOI:
10.3109/08923973.2014.960088
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发表时间:
2014-12-01
影响因子:
3.3
通讯作者:
Yuan, Ding
Yuan, Ding
中科院分区:
医学4区
文献类型:
--
作者:
Wang, Ting;Dai, Yanwen;Yuan, Ding

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巨噬细胞的过度活化与各种炎症导致的损伤有关。人参皂苷(SPJ)具有抗炎活性。然而,是否Chikusetsusaponin V(CsV),SPJ中最丰富的成分,可以发挥抗炎活性是未知的。本研究旨在探讨CsV对脂多糖(LPS)刺激的RAW 264.7巨噬细胞的抗炎作用及其机制。CsV剂量依赖性地抑制LPS刺激的RAW264.7细胞中NO、iNOS、TNF-α和IL-1 β的表达。在LPS刺激的RAW 264.7细胞中,核NF-κ B B蛋白水平的增加以及ERK和JNK磷酸化水平的升高也被CsV处理下调。CsV可明显逆转LPS刺激引起的CD 14和TLR 4 mRNA表达的增加。提示CsV通过TLR 4/CD 14介导的NF-κ B和MAPK途径减轻LPS诱导的炎症反应。
Excessive activation of macrophages is implicated in various inflammation resulted injuries. Saponins from Panax japonicus (SPJ) have been shown to possess anti-inflammatory activities. However, whether Chikusetsusaponin V (CsV), the most abundant component of SPJ, can exert anti-inflammatory activities is unknown. The present study was aimed to investigate the anti-inflammatory effects of CsV in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells and the underlying mechanisms. Our data showed that CsV dose-dependently inhibited NO, iNOS, TNF-alpha and IL-1 beta expressions in LPS-stimulated RAW264.7 cells. Increased protein levels of nuclear NF-kappa B and elevated phosphorylation levels of ERK and JNK in LPS-stimulated RAW 264.7 cells were also found downregulated by CsV treatment. Furthermore, the increase of CD14 and TLR4 mRNA expression due to LPS stimulation were significantly reversed by CsV treatment. These results suggested that CsV attenuated LPS-induced inflammatory responses partly via TLR4/CD14-mediated NF-kappa B and MAPK pathways.