Biomolecules & Therapeutics  https://doi.org/10.4062/biomolther.2020.195
3’-O-Acetyl-24-Epi-7,8-Didehydrocimigenol-3-O-β-D-Xylopryranoside Decreases Amyloid Beta Production in Amyloid Precursor Protein-Transfected HeLa Cells
Sang-Bin Lee1,2,†, Ansun Park2,3,†, Chi Thanh Ma4, Young Ho Kim5 and Hyun Ok Yang1,2,3,*
1Department of Integrative Biological Sciences and Industry, Sejong University, Seoul 05006,
2Natural Product Research Center, Korea Institute of Science and Technology, Gangneung 25451,
3Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul 02792, Republic of Korea
4Department of Pharmacognosy, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City 700000, Vietnam
5College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea
*E-mail: hoyang@sejong.ac.kr
Tel: +82-2-3408-1959, Fax: +82-2-3408-4336
The first two authors contributed equally to this work.
Received: November 2, 2020; Revised: December 16, 2020; Accepted: December 17, 2020; Published online: February 23, 2021.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
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.
Keywords: Alzheimer’s disease, Anti-amyloidogenic effect, Secretases


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