Department of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou 510000, China.
Molecules. 2013 Oct 21;18(10):13061-77. doi: 10.3390/molecules181013061.
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.
糖尿病肾病（DN）是糖尿病最常见和最严重的慢性并发症之一，但目前尚无有效的临床药物可用于治疗 DN。我们选择并合成了几种倍半萜内酯（SLs），然后使用 MTT 检测试剂盒检测大鼠肾小球系膜细胞（MCs）的增殖，使用 ELISA 试剂盒测量单核细胞趋化蛋白-1（MCP-1）、转化生长因子-β1（TGF-β1）和纤维连接蛋白（FN）的表达水平，使用实时荧光定量 PCR 分析测量 MCP-1 和 TGF-β1 基因表达，使用 Western blot 检测 IκBα 蛋白水平，使用 EMSA 测量核因子 kappa B（NF-κB）的激活。我们发现，SLs，包括小白菊内酯（PTL）、土木香内酯（MCL）、缬草烯醇、异土木香内酯（IAL）以及这些分子的几种合成类似物，能够有效抑制高糖刺激的 NF-κB 激活、IκBα 的降解以及大鼠肾小球系膜细胞（MCs）中 MCP-1、TGF-β1 和 FN 的表达。这些发现表明 SLs 及其衍生物具有作为治疗 DN 的候选药物的潜力。
