State Key Laboratory of Quality Research in Chinese Medicine, Biotechnology Labortory of Chinese Medicine, Macau University of Science and Technology, Taipa, Macau.
Phytother Res. 2012 Mar;26(3):412-9. doi: 10.1002/ptr.3569. Epub 2011 Jul 28.
Advanced glycation end-products (AGEs) have been regarded as an initial motivating factor in the pathogenesis of endothelial dysfunction in diabetic complications. 4,4'-Diphenylmethane-bis(methyl) carbamate (DMPC), a carbamate compound, was isolated from Cortex Mori and its prevention effects against AGEs-induced endothelial dysfunction were studied. 4,4'-Diphenylmethane-bis(methyl) carbamate significantly reduced cell apoptosis to normal level at 10⁻⁹ mol/L concentration. Advanced glycation end-products up-regulated the expression of Bad and Bax and down-regulated Bcl-2 proteins, and pretreatment with DMPC significantly down-regulated Bad and Bax while up-regulating Bcl-2 expressions. In addition, ICAM (intercellular adhesion molecule)-1 and TGF (transforming growth factor)-β1 expressions in human umbilical vein endothelial cell (HUVEC) were significantly enhanced by AGEs. More importantly, these increases of ICAM-1 and TGF-β1 expressions were reduced meaningfully with the pretreatment of DMPC. All the results showed DMPC had prevention effects against the progression of AGE-induced endothelial dysfunction, and this compound might be a promising agent against endothelial dysfunction in diabetic vascular complications.
糖基化终产物（AGEs）被认为是糖尿病并发症内皮功能障碍发病机制中的初始促发因素。4,4'-二苯基甲烷双（甲基）氨基甲酸酯（DMPC）是一种氨基甲酸酯化合物，从桑白皮中分离出来，研究了其对AGEs 诱导的内皮功能障碍的预防作用。在 10⁻⁹ mol/L 浓度下，DMPC 可显著将细胞凋亡降低至正常水平。糖基化终产物使 Bad 和 Bax 蛋白的表达上调，Bcl-2 蛋白的表达下调，而 DMPC 预处理可显著下调 Bad 和 Bax 的表达，同时上调 Bcl-2 的表达。此外，AGEs 可显著增强人脐静脉内皮细胞（HUVEC）中细胞间黏附分子-1（ICAM-1）和转化生长因子-β1（TGF-β1）的表达。更重要的是，DMPC 的预处理可显著降低 ICAM-1 和 TGF-β1 表达的增加。所有结果表明，DMPC 对 AGE 诱导的内皮功能障碍的进展具有预防作用，该化合物可能是治疗糖尿病血管并发症内皮功能障碍的一种有前途的药物。
