Abstract

BackgroundCompound Danshen Tablet (CDT), a Traditional Chinese Medicine, has recently been reported to improve spatial cognition in a rat model of Alzheimer’s disease. However, in vivo neuroprotective mechanism of the CDT in models of spatial memory impairment is not yet evaluated. The present study is aimed to elucidate the cellular mechanism of CDT on Aβ25-35-induced cognitive impairment in mice.MethodsMice were randomly divided into 5 groups: the control group (sham operated), the Aβ25-35 treated group, the positive drug group, and large and small dosage of the CDT groups, respectively. CDT was administered at a dose of 0.81 g/kg and 0.405 g/kg for 3 weeks. The mice in the positive drug group were treated with 0.4 mg/kg of Huperzine A, whereas the mice of the control and Aβ25-35 treated groups were administrated orally with equivalent saline. After 7 days of preventive treatment, mice were subjected to lateral ventricle injection of Aβ25-35 to establish the mice model of Alzheimer’s disease. Spatial memory impairment was evaluated by Morris water maze test. Choline acetyltransferase (ChAT) contents in hippocampus and cortex were quantified by ELISA. The levels of cytokines, receptor of activated protein kinase C1 (RACK1) and brain-derived neurotrophic factor (BDNF) in hippocampus were measured by RT-PCR and ELISA.ResultsThe results showed that Aβ25-35 caused spatial memory impairment as demonstrated by performance in the Morris water maze test. CDT was able to confer a significant improvement in spatial memory, and protect mice from Aβ25-35-induced neurotoxicity. Additionally, CDT also inhibited the increase of TNF-α and IL-6 level, and increased the expression of choline acetyltransferase (ChAT), receptor of activated protein kinase C1 (RACK1) and brain-derived neurotrophic factor (BDNF) in brain as compared to model mice.ConclusionThese findings strongly implicate that CDT may be a useful treatment against learning and memory deficits in mice by rescuing imbalance between cytokines and neurotrophins.

Highlights

  • Compound Danshen Tablet (CDT), a Traditional Chinese Medicine, has recently been reported to improve spatial cognition in a rat model of Alzheimer’s disease

  • Effects of Compound Danshen Tablets (CDT) on Aβ1-42 deposition in the hippocampus and cortex To confirm the effect of CDT on Aβ1-42 deposition in Amyloid β-protein fragment 25–35 (Aβ25-35) induced Alzheimer’s disease (AD) model in mice, we first examined the Aβ1-42 deposition in hippocampus and cortex of mice by enzyme-linked immuno sorbent assay (ELISA)

  • There was no significant difference between large dose of Compound Danshen Tablets group (LCDT) and Huperzine A group (P > 0.05, respectively) (Figure 1A)

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Summary

Introduction

Compound Danshen Tablet (CDT), a Traditional Chinese Medicine, has recently been reported to improve spatial cognition in a rat model of Alzheimer’s disease. In vivo neuroprotective mechanism of the CDT in models of spatial memory impairment is not yet evaluated. The present study is aimed to elucidate the cellular mechanism of CDT on Aβ25-35-induced cognitive impairment in mice. Many traditional herbal formulations have been reported to significantly improve cognitive function in clinical trials [11,12] and preclinical experiments [13], such as Compound Danshen Tablets (CDT) [14]. To the best of our knowledge, there is no available study that evaluates the effects of Compound Danshen Tablets (CDT) on neuroinflammation and neurotrophin levels in an experimental mice model of Alzheimer’s disease

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