Hyperphosphorylation of the microtubule-associated protein, tau, is critical to the progression of Alzheimer's disease (AD). Fuzheng Quxie Decoction (FQD), a Chinese herbal complex, is an effective clinical formula used to treat AD. In the current study, we employed high-performance liquid chromatography and liquid chromatography tandem mass spectrometry to identify the components of FQD. Three major components (ginsenoside Rg1, ginsenoside Re, and coptisine) were detected in the brain of FQD-fed mice, indicating their ability to cross the blood-brain barrier. We further evaluated the efficacy of FQD on Senescence-Accelerated Mice Prone-8 (SAMP8) mice. FQD significantly ameliorated learning and memory deficits in SAMP8 mice on the Morris Water Maze, decreasing escape latency (p < 0.01) and increasing swim time within the original platform-containing quadrant (p < 0.05). Further, FQD increased the number of neurons and intraneuronal Nissl bodies in the hippocampal CA1 region. FQD also decreased the expression of phosphorylated tau protein and increased the expression of protein phosphatase 2A (PP2A) and the N-methyl-D-aspartate receptor subunit, NR2A (p < 0.01). Our results indicate that FQD improves the learning and memory ability of SAMP8 mice. Moreover, our findings suggest that the protective effect of FQD is likely mediated through an inhibition of hippocampal tau hyperphosphorylation via NMDAR/PP2A-associated proteins.
Objective. Huannao Yicong Decoction (HYD, 还脑益聪方) has been shown to improve the learning and memory capabilities of Alzheimer's disease (AD) subjects. However, the underlying mechanism remains to be determined. Methods. Sixty Sprague-Dawley rats were divided equally and randomly into five different groups including control, positive control, and HYD granules of low dose, medium dose, and high dose by daily gavage. The sham-treated rats were also given the same volume of sterile water by gavage. Twelve SD rats were treated with the same amount of physiological saline. Twelve weeks later, learning and memory capabilities, Aβ content of the right brain and the expression of glycogen synthase kinase-3β (GSK-3β), total tau protein kinase (TTBK1), and cyclin-dependent kinase-5 (CDK-5) were tested. Results. Our results showed that high dose HYD treatment significantly improved the learning and memory capability of the AD rats and decreased the expression of TTBK1, GSK-3β, and CDK-5 in the hippocampal CA1 region. Conclusions. HYD treatment for 12 weeks significantly improved spatial learning and memory and effectively inhibited Aβ deposition, likely via reducing tau protein kinase expression and thus tau hyperphosphorylation and inflammatory injury. Taken together, these results suggest that HYD could be an effective treatment for AD.
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