Sesquiterpene lactones and their derivatives inhibit high glucose-induced NF-κB activation and MCP-1 and TGF-β1 expression in rat mesangial cells.
Sesquiterpene lactones and their derivatives inhibit high glucose-induced NF-κB activation and MCP-1 and TGF-β1 expression in rat mesangial cells.
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倍半萜内酯及其衍生物抑制大鼠肾小球细胞中高葡萄糖诱导的NF-κB激活以及MCP-1和TGF-β1的表达。
DOI：
10.3390/molecules181013061
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发表时间：
2013-10-21
期刊：
影响因子：
--
通讯作者：
Long HB
中科院分区：
文献类型：
--
作者：
Jia QQ;Wang JC;Long J;Zhao Y;Chen SJ;Zhai JD;Wei LB;Zhang Q;Chen Y;Long HB
糖尿病肾病（Diabetic nephropathy， DN）是糖尿病最常见、最严重的慢性并发症之一，目前尚无有效的临床治疗药物。我们选择并合成了几种倍半萜内酯（SLs），然后用MTT法检测大鼠系膜细胞（MCs）的增殖，ELISA法检测单核细胞趋化蛋白-1 （MCP-1）、转化生长因子β (TGF-β1)和纤维连接蛋白（FN）的表达水平，实时荧光定量PCR法检测MCP-1和TGF-β1基因的表达。western blot检测i -κB α蛋白水平，EMSA检测核因子κB （NF-κB）活化水平。我们发现，包括parthenolide (PTL), micheliolide (MCL), arglabin，和isoalantolactone （IAL）在内的SLs，以及这些分子的几种合成类似物，可以有效地减弱高糖刺激下大鼠系膜细胞（MCs）中NF-κB的激活，i -κB α的降解，以及MCP-1， TGF-β1和FN的表达。这些发现表明，SLs及其衍生物有潜力作为治疗DN的候选药物。
Diabetic nephropathy (DN) is one of the most common and serious chronic complications of diabetes mellitus, however, no efficient clinical drugs exist for the treatment of DN. We selected and synthesized several sesquiterpene lactones (SLs), and then used the MTT assay to detect rat mesangial cells (MCs) proliferation, ELISA to measure the expression level of monocyte chemoattractant protein-1 (MCP-1), transforming growth factor beta (TGF-β1) and fibronectin(FN), real-time fluorescent quantitative PCR analysis to measure the MCP-1 and TGF-β1 gene expression, western blot to detect the level of IκBα protein and EMSA to measure the activation of nuclear factor kappa B (NF-κB). We discovered that SLs, including parthenolide (PTL), micheliolide (MCL), arglabin, and isoalantolactone (IAL), as well as several synthetic analogs of these molecules, could effectively attenuate the high glucose-stimulated activation of NF-κB, the degradation of IκBα, and the expression of MCP-1, TGF-β1 and FN in rat mesangial cells (MCs). These findings suggest that SLs and their derivatives have potential as candidate drugs for the treatment of DN.
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