Paeoniflorin exerts neuroprotective effects in a transgenic mouse model of Alzheimer's disease via activation of adenosine A1 receptor. (21st June 2020)

• Record Type: Journal Article
• Authors: Kong, Yanying; Peng, Qiuju; Lv, Nan; Yuan, Jin; Deng, Zhirong; Liang, Xiaolin; Chen, Si; Wang, Laiyou
• Is Part Of: Neuroscience letters. Volume 730(2020)
• Publication Date: 2020-06-21
• Subjects: 5XFAD transgenic mice with five familial AD mutations -- A1R adenosine A1 receptor -- Aβ amyloid β -- AD alzheimer's disease -- DPCPX 13-dipropyl-8-cyclopentylxanthine -- GFAP glial fibrillary acidic protein -- IL interleukin -- MWM morris water maze -- PDE phosphodiesterase -- PF paeoniflorin -- TNF tumor necrosis factor; Alzheimer's disease -- Paeoniflorin -- 5XFAD mouse model -- Adenosine A1 receptor; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2020.135016
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Study of anti-dementia properties of paeoniflorin (PF) in 5XFAD mouse model. PF ameliorated cognitive deficit, Aβ plaques deposition, and astrocyte activation. Activation of adenosine A1 R may influence the neuroprotective effects of PF. PF can potentially be a therapeutic agent for the treatment of AD. Abstract: Alzheimer's disease (AD) is the most common cause of dementia, characterised by advanced cognitive and memory deterioration with no effective treatments available. Previous in vitro and in vivo studies suggest that paeoniflorin (PF), a major bioactive constituent of Radix Paeoniae, might possess anti-dementia properties; however, the underlying mechanism remains unclear. The aim of the current study was to determine the therapeutic effects of PF in a transgenic mouse model of AD and to identify its mechanism. Transgenic mice with five familial AD mutations (5XFAD) were used in this study. We showed that 28 days of PF (5 mg/kg, ip) treatment significantly decreased the escape latency and path length in the Morris water maze test and increased the alternation rate in the T-maze test, compared to the vehicle treatment group. In addition, PF treatment significantly alleviated amyloid β plaque burden, inhibited astrocyte activation, and decreased IL-1β and TNF-α expression in the brain of 5XFAD mice. However, the anti-cognitive deficits, anti-amyloidogenic, and anti-inflammatory effects of PF were abolished by 1, 3-dipropyl-8-cyclopentylxanthine (DPCPX, 0.3 mg/kg), an adenosine A1 receptor (A1 R) antagonist. In conclusion, our results suggest that PF might act as a potential therapeutic agent for AD via activation of adenosine A1 R.