School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, Anhui, China (mainland).
Department of Pharmacy, Zhuhai Hospital of Guangdong General Hospital, Zhuhai, Guangdong, China (mainland).
Med Sci Monit. 2018 Feb 28;24:1219-1224. doi: 10.12659/msm.905127.
BACKGROUND Beta-secretase 1 (BACE1) is a rate-limiting enzyme in the generation of amyloid beta peptides, which are associated with Alzheimer's disease (AD). It has been reported that Schisandrin B could improve cognitive functions in animal models of AD, but the underlying mechanisms are not completely understood. MATERIAL AND METHODS In this research, in order to investigate the effects of Schisandrin B on amyloid-β (Aβ) metabolism and its mechanisms, amyloid precursor protein (APP) and its proteolytic products were determined by enzyme-linked immunosorbent assay (ELISA), western blotting, and RT-PCR after incubation of N2a/Swe cells with Schisandrin B. RESULTS The results indicated that Schisandrin B can significantly reduce the level of secretion of Aβ40 and Aβ42 secreted in N2a/Swe cells. Additionally, there was nonsignificant change in APP level after Schisandrin B treatment. Treatment of Schisandrin B dramatically reduced the mRNA and protein expression levels of BACE1. Moreover, Schisandrin B treatment resulted in a reduction of protein level of sAPPβ, an APP fragment cleavage by BACE1. CONCLUSIONS These results suggest that Schisandrin B inhibits the transcription and translation of BACE1, suppresses the activity of BACE1, and ultimately attenuates Aβ generation, which provides a novel mechanism for the regulation of Aβ metabolism by Schisandrin B.
β-分泌酶 1（BACE1）是淀粉样β肽生成的限速酶，与阿尔茨海默病（AD）有关。有报道称，五味子素 B 可改善 AD 动物模型的认知功能，但作用机制尚不完全清楚。
在这项研究中，为了研究五味子素 B 对淀粉样β（Aβ）代谢的影响及其机制，我们通过酶联免疫吸附试验（ELISA）、Western blot 和 RT-PCR 检测 N2a/Swe 细胞孵育五味子素 B 后 APP 及其蛋白水解产物。
结果表明，五味子素 B 可显著降低 N2a/Swe 细胞中分泌的 Aβ40 和 Aβ42 的水平。此外，五味子素 B 处理后 APP 水平无明显变化。五味子素 B 处理可显著降低 BACE1 的 mRNA 和蛋白表达水平。此外，五味子素 B 处理可降低 BACE1 切割的 APP 片段 sAPPβ的蛋白水平。
这些结果表明，五味子素 B 通过抑制 BACE1 的转录和翻译，抑制 BACE1 的活性，最终减少 Aβ的生成，为五味子素 B 调节 Aβ代谢提供了新的机制。
