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.
PurposeThis study was designed to explore the underlying mechanism of action for a Fuzheng Quxie Decoction (FQD) in Alzheimer’s disease (AD), to validate its neuroprotective effects, and to provide experimental support for its predicted mechanism of action.MethodsAn integrative approach to network pharmacology was performed to predict the mechanism of action for treatment of AD with FQD. The predicted mechanism was validated in SAMP8 mice.ResultsWith predicted putative FQD targets and a collection of AD-related genes, 245 possible regulatory targets of FQD were identified for the treatment of AD. Pathway-enrichment analysis for the possible regulatory targets indicated that vascular endothelial growth factor (VEGF) and VEGF-receptor signaling were pivotal in the treatment of AD with FQD. In vivo experiments confirmed the neuroprotective effect and the predicted mechanism of action for treatment of AD with FQD.ConclusionThis study contributes to an understanding of the neuroprotective effect of FQD and its potential mechanism of action for the treatment of AD.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.