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Anti-amyloidgenic and neurotrophic effects of tetrahydroxystilbene glucoside on a chronic mitochondrial dysfunction rat model induced by sodium azide

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Abstract

Alzheimer’s disease (AD) is an irreversible neurodegenerative brain disorder with complex pathogenesis. Emerging evidence indicates that there is a tight relationship between mitochondrial dysfunction and β-amyloid (Aβ) formation. 2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG) is one of the main active components extracted from Polygonum multiflorum. The purpose of the present study was to investigate the effects of TSG on Aβ production and neurotrophins in the brains of rats by using a mitochondrial dysfunction rat model induced by sodium azide (NaN3), an inhibitor of mitochondrial cytochrome c oxidase (COX). NaN3 was administered to rats by continuous subcutaneous infusion for 28 days via implanted osmotic minipumps to establish the animal model. TSG was intragastrically administered starting 24 h after the operation. The activity of mitochondrial COX was measured by a biochemical method. The content of Aβ 1-42 was detected by ELISA. The expression of neurotrophic factors was determined by Western blot and immunohistochemistry. The results showed that NaN3 infusion for 28 days induced a decrease in mitochondrial COX activity, an increase in Aβ 1-42 content and the expression of amyloidogenic β-amyloid precursor protein (APP), beta-site APP cleaving enzyme 1 (BACE1) and presenilin 1 (PS1), and a decline in the expression of neurotrophins in the hippocampus of rats. Intragastrical administration of TSG elevated mitochondrial COX activity, decreased Aβ 1-42 content and the expression of APP, BACE1 and PS1, and enhanced the expression of nerve growth factor, brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase B (TrkB) in the hippocampus of NaN3-infused rats. These findings suggest that TSG may be beneficial in blocking or slowing the progression of AD by enhancing mitochondrial function, decreasing Aβ production and increasing neurotrophic factors at some extent.

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Acknowledgements

This research was supported by the National Natural Science Foundation of China (Nos. 81273498, 81341087, 81473373); the National Science and Technology Major Project of China (No. 2015ZX09101-016); the Capital Health Research and Development Foundation (Nos. 2011-1001-04, 2016-2-1033); the Beijing New Medical Discipline Grant (XK100270569); and the Beijing High-level Health and Technical Personal Plan (Nos. 2011-1-7, 2014-2-014). We thank Ya-li Li and Hou-xi Ai for their technical assistance.

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  1. Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Beijing Geriatric Medical Research Center, Beijing Institute for Brain Disorders, Beijing Engineering Research Center for Nerve System Drugs, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, 100053, China

    Ru-yi Zhang, Lan Zhang, Li Zhang & Lin Li

  2. Department of Central Lab, Xuanwu Hospital of Capital Medical University, Beijing, China

    Yu-lan Wang

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  1. Ru-yi Zhang
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Zhang, Ry., Zhang, L., Zhang, L. et al. Anti-amyloidgenic and neurotrophic effects of tetrahydroxystilbene glucoside on a chronic mitochondrial dysfunction rat model induced by sodium azide. J Nat Med 72, 596–606 (2018). https://doi.org/10.1007/s11418-018-1177-y

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