Abstract
ABSTRACTThe aim of this study was to investigate the mechanism of action underlying the effect of polysaccharide from Vitis vinifera L. (VTP) on the nuclear factor kappa B/inhibitor kappa B alpha (NF-κB/IκB-α) signaling pathway and related inflammatory factors in hippocampus of rats with Alzheimer's disease (AD). Amyloid-β 25–35 was injected into the hippocampus to establish AD model rats, and the rats were administered with donepezil and VTP. The levels of interleukin-1β, interleukin-6 and tumour necrosis factor-α in the serum were determined by enzyme-linked immunosorbent assay. The phosphorylation level, protein and gene expression of NF-κBp65 and IκB-α in hippocampus were detected by immunohistochemistry, western blot and real-time quantitative polymerase chain reaction (PCR), respectively. VTP effectively improved the learning and memory ability of AD rats. Transmission electron microscopy indicated that VTP reduced the toxic effects of amyloid-β 25–35 on neurons in AD rats. Enzyme-linked immunosorbent assay showed that VTP inhibited the expression of interleukin-1β, interleukin-6 and tumour necrosis factor-α in a dose-dependent manner. Compared with the model group, the expression levels of NF-κBp65 in the nucleus of the VTP group decreased, which was consistent with the Western blotting results. The expression of p-IκB-α and IκB-α, and, the mRNA level of NF-κBp65 and IκB-α in VTP group were significantly decreased compared to that in the model group, indicating that VTP has a therapeutic effect on AD. Its mechanism may be related to the inhibition of inflammatory response.
Highlights
The main pathological features of Alzheimer’s disease (AD), a neurodegenerative disease, include neurofibrillary tangles and senile plaques, which further induce inflammation [1]
In the space exploration experiment, the percentage of the retention time spent in the third quadrant and the number of times the rats crossed the effective area in the model group were significantly decreased compared to that of the control group (p < 0.01, Figure 1(C,D)); whereas the percentage of the retention time and the number of crossing times of the donepezil and low, medium and high-dose VTP groups were increased compared to those of the model group
These results suggest that VTP effectively improved the learning and memory ability of AD rats
Summary
The main pathological features of Alzheimer’s disease (AD), a neurodegenerative disease, include neurofibrillary tangles and senile plaques, which further induce inflammation [1]. A large number of activated glial cells and obvious inflammatory markers such as interleukin (IL)-1b, IL-6 and tumour necrosis factor (TNF)-a are found around senile plaques in the brains [2,3]. The phosphorylation and degradation of IkB-a as well as nuclear accumulation of NF-kB result in increased NF-kB activity, which further induces the production of a large number of inflammatory factors (IL-1b, IL-6 and TNF-a) [8,9]. These inflammatory factors induce a series of inflammatory reactions that cause neuronal damage [8,9]
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