Spinosin Inhibits Aβ1-42 Production and Aggregation via Activating Nrf2/HO-1 Pathway
Xiaoying Zhang1, Jinyu Wang1, Guowei Gong2, Ruixin Ma1, Fanxing Xu3, Tingxu Yan4, Bo Wu4 and Ying Jia4,*
1Key Laboratory of Active Components of Chinese Medicine Screening and Evaluation, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016,
2Department of Bioengineering, Zunyi Medical University, Zhuhai Campus, Zhuhai, Guangdong 519041,
3Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016,
4Key Laboratory of Active Components of Chinese Medicine Screening and Evaluation, School of Functional Food and Wine,Shenyang Pharmaceutical University, Shenyang 110016, China
*E-mail: jiayingsyphu@126.com
Tel: +86-24-2398-6933, Fax: +86-24-2398-6259
Received: July 21, 2019; Revised: October 12, 2019; Accepted: October 15, 2019; Published online: December 3, 2019.
© The Korean Society of Applied Pharmacology. All rights reserved.

The present research work primarily investigated whether spinosin has the potential of improving the pathogenesis of Alzheimer’s disease (AD) driven by β-amyloid (Aβ) overproduction through impacting the procession of amyloid precursor protein (APP). Wild type mouse Neuro-2a cells (N2a/WT) and N2a stably expressing human APP695 (N2a/APP695) cells were treated with spinosin for 24 h. The levels of APP protein and secreted enzymes closely related to APP procession were examined by western blot analysis. Oxidative stress related proteins, such as nuclear factor-erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) were detected by immunofluorescence assay and western blot analysis, respectively. The intracellular reactive oxygen species (ROS) level was analyzed by flow cytometry, the levels of Aβ1-42 were determined by ELISA kit, and Thioflavin T (ThT) assay was used to detect the effect of spinosin on Aβ1-42 aggregation. The results showed that ROS induced the expression of ADAM10 and reduced the expression of BACE1, while spinosin inhibited ROS production by activating Nrf2 and up-regulating the expression of HO-1. Additionally, spinosin reduced Aβ1-42 production by impacting the procession of APP. In addition, spinosin inhibited the aggregation of Aβ1-42. In conclusion, spinosin reduced Aβ1-42 production by activating the Nrf2/HO-1 pathway in N2a/WT and N2a/ APP695 cells. Therefore, spinosin is expected to be a promising treatment of AD.
Keywords: Alzheimer’s disease, Spinosin, Nrf2/HO-1, Neuroprotection

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