Biomol Ther.  2020 May;28(3):259-266. 10.4062/biomolther.2019.123.

Spinosin Inhibits Aβ1-42 Production and Aggregation via Activating Nrf2/HO-1 Pathway

• Zhang X
• Wang J
• Gong G
• Ma R
• Xu F
• Yan T
• Wu B
• Jia Y

• KMID: 2500502
• DOI: http://doi.org/10.4062/biomolther.2019.123

Abstract

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.

Keyword

Alzheimer’s disease; Spinosin; Nrf2/HO-1; Neuroprotection