中文摘要：

原小檗碱是一类异喹啉生物碱，具有相同的药效基团。本研究检测了以小檗碱和四氢黄藤素为代表的原小檗碱多靶点抗AD效应及分子作用机制。以人神经母细胞瘤SH—SY5Y为研究对象，利用Westernblot检测药物对细胞全长APP和BACE1蛋白水平的影响；ELISA技术检测细胞外可溶性淀粉样前体蛋白α（sAPPα）的分泌；酶活性检测试剂盒检测乙酰胆碱酯酶（AChE）的活性。结果显示，药物处理细胞24h后，二者均能显著地抑制BACE1蛋白的表达，并可使sAPPct的分泌显著增加，但未见细胞APP蛋白含量明显变化，同时对该细胞的AchE的活性具有显著的抑制作用。以上结果证明：原小檗碱生物碱药理活性涉及预防和减少AB沉积和增强乙酰胆碱对脑胆碱受体的作用，并通过细胞自身的代谢增加具有神经营养作用的sAPPer的分泌。提示此类化合物具有多靶点抗老年痴呆的潜能，通过结构优化改造，将有望获得副作用小的新一代抗AD有效药物。

英文摘要：

Proberberine is an isoquinoline alkaloid with the same pharmacophore. In this studies we explored the Multi-targeted effect of Berberine and tetrahydropalmatine （THP） which are representative of probererine, and their molecular mechanisms of anti-Alzheimer＇s disease. SH-SYSY cells were treated with Berberine or THP, the BACE1 protein level, the secretion of sAPPα and the AChE activity were respectively measured by western blot analysis, ELISA assay and AChE activity detection kit. The results showed that, after drug treatments for 24 hours, both Berberine and THP can significantly inhibit the expression of BACE1, increase the secretion of sAPPer, and decrease the AChE activity, but not change full length APP protein lever. These results demonstrated that the pharmacological effects of Proberberine were involved in prevention and reduction of Aβ level, enhancement of the effect of acetylcholine on acetyleholine receptor in the brain, and increase of the secretion of neurotrophic sAPPα. Our results suggest that Proberberine has multi-target-directed therapeutical potential on Alzheimer＇s disease, and through struc- tural optimization, it is promising for the development of new anti-AD drugs with less side effects.