Key Laboratory of Bioactive Substances and Resources Utilization, Ministry of Education, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xiannongtan street, Xuanwu district, Beijing 100050, China.
Neurosci Lett. 2010 Oct 8;483(1):78-82. doi: 10.1016/j.neulet.2010.07.067. Epub 2010 Jul 30.
The neurotoxicity of aggregated beta-amyloid (Abeta) has been implicated as a critical cause in the pathogenesis of Alzheimer's disease (AD). In the present study, we investigated the effect of (-)clausenamide ((-)Clau), an aqueous extract of leaves of Clausena lassium (lour) skeel, on the neurotoxicity of Abeta(25-35). The viability of differentiated PC12 cells was determined by MTT assay. Apoptosis was detected by flow cytometry. DCFH-DA was used for assessment of intracellular ROS generation, JC-1 and Rhodamine 123 for measurement of mitochondrial transmembrane potential (MMP). The intracellular calcium was determined with Fluo-3. The phosphorylation of p38 MAPK and the expression of Bcl-2, Bax, P53, Caspase 3 were examined by Western blot. The results showed that (-)Clau significantly elevated cell viability. Furthermore, (-)Clau arrested the apoptotic cascade by reversing overload of calcium, preventing ROS generation, moderated the dissipation of MMP and the misbalance of Bcl-2 and Bax, inhibiting the activation of p38 MAPK and the expression of P53 and cleaved Caspase 3. Our results suggested that (-)Clau may be a therapeutic agent for AD.
聚集态β-淀粉样蛋白（Abeta）的神经毒性被认为是阿尔茨海默病（AD）发病机制中的一个关键原因。在本研究中，我们研究了（-）克拉散胺（（-）Clau），即罗望子（lour）skeel 叶的水提物对 Abeta（25-35）神经毒性的影响。通过 MTT 测定法测定分化的 PC12 细胞的活力。通过流式细胞术检测细胞凋亡。使用 DCFH-DA 评估细胞内 ROS 的产生，使用 JC-1 和 Rhodamine 123 测量线粒体跨膜电位（MMP）。用 Fluo-3 测定细胞内钙离子。通过 Western blot 检测 p38 MAPK 的磷酸化和 Bcl-2、Bax、P53、Caspase 3 的表达。结果表明，（-）Clau 显著提高了细胞活力。此外，（-）Clau 通过逆转钙超载、防止 ROS 产生、调节 MMP 耗散以及平衡 Bcl-2 和 Bax、抑制 p38 MAPK 的激活和 P53 和裂解 Caspase 3 的表达，阻止了细胞凋亡级联反应。我们的结果表明，（-）Clau 可能是 AD 的治疗剂。
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