Abstract

BackgroundSenile dementia mainly includes Alzheimer' s disease (AD) and vascular dementia (VD). AD is a progressive and irreversible neurodegenerative disorder that is accompanied with a great deal of social burden. The aim of this study was to investigate the effect of Compound Danshen (CDS) on learning and memory of alzheimer’s disease (AD) rat model, as well as to explore the possible connection between CDS and the associated molecules of amyloid beta (Aβ).MethodsRats were injected with Aβ25–35 peptide intracerebroventricularly and CDS were subsequently administered once daily for 23 days. Rats’ behavior was monitored using Morris water maze and passive avoidance. Real time PCR and Western blotting were used in determining amyloid precursor protein (APP), β-site APP cleaved enzyme-1(BACE1), Presenilin-1 (PS1), Insulin-degrading enzyme (IDE) and neprilysin (NEP) in hippocampus.ResultsThe AD model group presented with spatial learning and memory impairments. CDS and donepezil administration significantly ameliorated the Aβ25–35 peptide-induced memory impairment in both Morris water maze (P < 0.05) and passive avoidance task (P < 0.01) compared to the AD model group. Real time PCR results suggested that CDS significantly decreased APP mRNA, PS1 mRNA and increased IDE and NEP mRNA levels. Western blotting analyses showed that CDS decreased the protein expression of APP and PS1 and increased IDE expression.ConclusionCDS improved spatial learning and memory by down-regulating APP, PS1 levels and up-regulating IDE. In future, CDS may have significant therapeutic potential in the treatment of AD patients.

Highlights

  • Senile dementia mainly includes Alzheimer' s disease (AD) and vascular dementia (VD)

  • Salvia miltiorrhiza (450 g), Notoginseng (141 g) and Borneolum Syntheticum (8 g), were extracted with 4.8 L ethanol heating reflux for 1.5 h, filtered, ethanol were recycled and filtered solution were concentrated to moderate volume; the dregs were extracted with 4.8 L 50 % ethanol heating reflux for 1.5 h, filtered, ethanol were recycled and filtrate were concentrated to moderate volume; dregs were extracted with 3.6 L water for 2 h, filtered, filtrate were concentrated to moderate volume; Radix Notoginseng were crushed into fine powder, combined with the above concentrate solution and the moderate auxiliary materials made into grain, dried; Borneolum Syntheticum were porphyrized, blending with the grain

  • Effect of Compound Danshen (CDS) on Aβ25–35-induced memory deficit in the Morris water maze test To evaluate the effect of CDS on Aβ25–35-induced spatial memory deficit, we examined memory performance of rats treated with CDS, Donepezil and vehicle in the Morris water maze test

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Summary

Introduction

Senile dementia mainly includes Alzheimer' s disease (AD) and vascular dementia (VD). Liu et al BMC Complementary and Alternative Medicine (2015) 15:382. It appears that accumulation of Aβ can theoretically occur because of insufficient clearance of Aβ [6]. NEP and IDE have been studied most extensively. Similar to NEP, genetic deletion of IDE in mice increases cerebral Aβ levels [8]. Their critical role in neurodegenerative disease has been demonstrated in NEP- and IDE-knockout animals [9]

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