Cognitive improvement of compound danshen in an Aβ25-35 peptide-induced rat model of Alzheimer's disease.
BACKGROUND
Senile 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).


METHODS
Rats 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.


RESULTS
The 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.


CONCLUSIONS
CDS 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.
Modern Chinese Medicine Research Institute of Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Co., Ltd., Guangzhou, 510515, Guangdong Province, China.|Department of Pharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, Guangdong Province, China.|Post Doctoral Scientific Research Center, Guangzhou Pharmaceutical Corporation, Guangzhou, 510515, Guangdong Province, China.
Min
M
Liu
Department of Pharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, Guangdong Province, China.
Haibiao
H
Guo
Modern Chinese Medicine Research Institute of Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Co., Ltd., Guangzhou, 510515, Guangdong Province, China.
Chuyuan
C
Li
Modern Chinese Medicine Research Institute of Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Co., Ltd., Guangzhou, 510515, Guangdong Province, China.
Deqin
D
Wang
Department of Pharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, Guangdong Province, China.
Jingang
J
Wu
Department of Pharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, Guangdong Province, China.
Canmao
C
Wang
Department of Pharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, Guangdong Province, China. jpx@smu.edu.cn.
Jiangping
J
Xu
Modern Chinese Medicine Research Institute of Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Co., Ltd., Guangzhou, 510515, Guangdong Province, China. qinrenan@813zy.com.
Ren-An
RA
Qin
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D003071:Cognition / Q000187:drug effects*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism; D007858:Learning / Q000187:drug effects; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D027561:Salvia miltiorrhiza
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D004365:Drugs, Chinese Herbal; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35)