Lee Sang-Bin, Park Ansun, Ma Chi Thanh, Kim Young Ho, Yang Hyun Ok
Department of Integrative Biological Sciences and Industry, Sejong University, Seoul 05006, Republic of Korea.
Natural Product Research Center, Korea Institute of Science and Technology, Gangneung 25451, Republic of Korea.
Biomol Ther (Seoul). 2021 May 1;29(3):290-294. doi: 10.4062/biomolther.2020.195.
Extracellular beta amyloid (Aβ) plaques are the neuropathological hallmarks of Alzheimer's disease (AD). Accordingly, reducing Aβ levels is considered a promising strategy for AD prevention. 3'-O-acetyl-24-epi-7,8-didehydrocimigenol-3-O-β-D-xylopryranoside significantly decreased the Aβ production and this effect was accompanied with reduced sAPPβ production known as a soluble ectodomain APP fragment through β-secretases in HeLa cells overexpressing amyloid precursor proteins (APPs). This compound also increased the level of sAPPα, which is a proteolytic fragment of APP by α-secretases. In addition, 3'-O-acetyl-24-epi-7,8-didehydrocimigenol-3-O-β-D-xylopryranoside decreased the protein level of β-secretases, but the protein levels of A disintegrin and metalloproteinase (ADAM) family, especially ADAM10 and ADAM17, are increased. Thus, 3'-O-acetyl-24-epi-7,8-didehydrocimigenol-3-O-β-D-xylopryranoside could be useful in the development of AD treatment in the aspect of amyloid pathology.
细胞外β淀粉样蛋白(Aβ)斑块是阿尔茨海默病(AD)的神经病理学标志。因此,降低Aβ水平被认为是预防AD的一种有前景的策略。3'-O-乙酰基-24-表-7,8-二脱氢升麻醇-3-O-β-D-吡喃木糖苷显著降低了Aβ的产生,并且在过表达淀粉样前体蛋白(APP)的HeLa细胞中,这种作用伴随着通过β-分泌酶产生的可溶性胞外域APP片段sAPPβ的减少。该化合物还增加了sAPPα的水平,sAPPα是APP经α-分泌酶作用产生的蛋白水解片段。此外,3'-O-乙酰基-24-表-7,8-二脱氢升麻醇-3-O-β-D-吡喃木糖苷降低了β-分泌酶的蛋白水平,但增加了整合素和金属蛋白酶(ADAM)家族的蛋白水平,尤其是ADAM10和ADAM17。因此,3'-O-乙酰基-24-表-7,8-二脱氢升麻醇-3-O-β-D-吡喃木糖苷在淀粉样病理方面可能对AD治疗的开发有用。