Anti-inflammatory effects of sophocarpine in LPS-induced RAW 264.7 cells via NF-κB and MAPKs signaling pathways
Anti-inflammatory effects of sophocarpine in LPS-induced RAW 264.7 cells via NF-κB and MAPKs signaling pathways
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DOI：
10.1016/j.tiv.2011.09.019
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发表时间：
2012-02-01
影响因子：
3.2
通讯作者：
Shen, Jingyu
中科院分区：
文献类型：
--
作者：
Gao, Yonglin;Jiang, Wanglin;Shen, Jingyu
槐果碱是苦豆子中含量最丰富的活性成分之一，是一种四环喹里西啶类生物碱。我们以前的研究表明槐果碱在动物模型中具有抗炎活性。本研究以脂多糖（LPS）诱导的RAW 264.7细胞为模型，探讨槐果碱的抗炎机制。并对槐果碱进行了细胞毒性试验。结果表明，槐果碱在800 μ g/ml浓度时，可明显升高LDH水平，抑制细胞活力，且远高于临床有效剂量的槐果碱血药浓度。结果还表明槐果碱（50和100 μ g/ml）抑制LPS刺激的NO产生和促炎细胞因子分泌，包括肿瘤坏死因子α（TNF-α）和白细胞介素-6（IL-6）。这些变化与诱导型一氧化氮合酶（iNOS）和环氧合酶-2（考克斯-2）表达减少有关。此外，槐果碱通过阻止抑制剂kappa B（I kappa B）磷酸化来抑制LPS介导的核因子-κ B（NF-κ B）活化。槐果碱对LPS诱导的细胞外信号调节激酶1/2（Erk 1/2）的磷酸化无影响，但可减弱p38丝裂原活化蛋白（MAP）激酶和c-Jun氨基末端激酶（JNK）的磷酸化。槐果碱具有抗炎作用，其机制可能与抑制JNK和p38 MAP激酶信号通路，抑制NF-κ B B活化，抑制iNOS和考克斯-2表达有关。(C)2011爱思唯尔有限公司保留所有权利。
Sophocarpine, a tetracyclic quinolizidine alkaloid, is one of the most abundant active ingredients in Sophora alopecuroides L. Our previous studies have showed that sophocarpine exerts anti-inflammatory activity in animal models. In the present study, anti-inflammatory mechanisms of sophocarpine were investigated in lipopolysaccharide (LPS)-induced responses in RAW 264.7 cells. Furthermore, the cytotoxicity of sophocarpine was tested. The results indicated that sophocarpine could increase the LDH level and inhibit cell viability up to 800 mu g/ml, and which was far higher than that of the plasma concentration of sophocarpine in clinical effective dosage. The results also demonstrated that sophocarpine (50 and 100 mu g/ml) suppressed LPS-stimulated NO production and pro-inflammatory cytokines secretion, including tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). These were associated with the decrease of the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, sophocarpine inhibited LPS-mediated nuclear factor-kappa B (NF-kappa B) activation via the prevention of inhibitor kappa B (I kappa B) phosphorylation. Sophocarpine had no effect on the LPS-induced phosphorylation of extracellular signal-regulated kinase 1/2 (Erk1/2), whereas it attenuated the phosphorylation of p38 mitogen-activated protein (MAP) kinase and c-Jun NH2-terminal kinase (JNK). Our data suggested that sophocarpine exerted anti-inflammatory activity in vitro, and it might attribute to the inhibition of iNOS and COX-2 expressions via down-regulation of the JNK and p38 MAP kinase signal pathways and inhibition of NF-kappa B activation. (C) 2011 Elsevier Ltd. All rights reserved.