Park Hanbyeol, Yoo Jong-Su, Kim Ji-Young, Hwang Bang Yeon, Han Jung-Soo, Yeon Seung-Woo, Kang Jae-Hoon
ILDONG Research Laboratories, ILDONG Pharmaceutical Co. Ltd., Hwaseong, Gyeonggi 445-710, Republic of Korea.
College of Pharmacy, Chungbuk National University, Cheongju 361-763, Republic of Korea.
Environ Toxicol Pharmacol. 2014 Mar;37(2):513-20. doi: 10.1016/j.etap.2014.01.008. Epub 2014 Jan 22.
Amyloid beta (Aβ) peptides, which are generated from amyloid precursor protein (APP), are thought to play a major role in the pathogenesis of Alzheimer's disease (AD). This study investigated the anti-amyloidogenic effects of the ethanolic extract of Meliae Fructus (ID1201) using human embryonic kidney 293 cells with stably expressed human wild-type or Swedish mutant APP695 and β-secretase 1. ID1201 treatment enhanced the non-amyloidogenic metabolism of APP; increases in soluble APPα levels and decreases in soluble APPβ and Aβ levels resulted from the α-secretase activation through the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. In addition, ID1201-treated 5×familial AD (FAD) mice with 5 mutations in APP and presenilin 1 showed reduced levels of Aβ and amyloid plaques in the brain relative to those of 5×FAD mice with vehicle treatments. These results indicate that ID1201 possesses anti-amyloidogenic effects via the activation of the PI3K/Akt pathway, suggesting that it is a potential therapeutic agent for AD.
淀粉样β（Aβ）肽由淀粉样前体蛋白（APP）生成，被认为在阿尔茨海默病（AD）的发病机制中起主要作用。本研究使用稳定表达人野生型或瑞典突变型APP695和β-分泌酶1的人胚肾293细胞，研究了苦楝果实乙醇提取物（ID1201）的抗淀粉样蛋白生成作用。ID1201处理增强了APP的非淀粉样蛋白生成代谢；通过磷脂酰肌醇3-激酶（PI3K）/Akt途径激活α-分泌酶，导致可溶性APPα水平升高，可溶性APPβ和Aβ水平降低。此外，与接受载体处理的5×家族性AD（FAD）小鼠相比，用ID1201处理的在APP和早老素1中有5个突变的5×FAD小鼠脑内Aβ和淀粉样斑块水平降低。这些结果表明，ID1201通过激活PI3K/Akt途径具有抗淀粉样蛋白生成作用，提示它是AD的一种潜在治疗药物。
