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. 2018 Nov 9:14:3037-3051.
doi: 10.2147/NDT.S175484. eCollection 2018.

The Chinese herbal formula Fuzheng Quxie Decoction attenuates cognitive impairment and protects cerebrovascular function in SAMP8 mice

Feixue Wang  1 , Jianchao Feng  2 , Yang Yang  1 , Jiangang Liu  3 , Meixia Liu  1 , Zhiyong Wang  1 , Hui Pei  1 , Yun Wei  1 , Hao Li  1
Affiliations

The Chinese herbal formula Fuzheng Quxie Decoction attenuates cognitive impairment and protects cerebrovascular function in SAMP8 mice

Feixue Wang et al. Neuropsychiatr Dis Treat. .

Abstract

Purpose: This 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.

Methods: An 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.

Results: With 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.

Conclusion: This study contributes to an understanding of the neuroprotective effect of FQD and its potential mechanism of action for the treatment of AD.

Keywords: Alzheimer’s disease; Fuzheng Quxie Decoction; hypoxia-induced factor 1α; microcerebrovascular; network pharmacology; vascular endothelial growth factor.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
The position of platform and entry points in the MWM test. Abbreviation: MWM, Morris water maze.
Figure 2
Figure 2
Intersections of putative FQD targets and AD-related genes; 32 shared genes were obtained, which were defined as DRTs. Abbreviations: AD, Alzheimer’s disease; DRTs, direct regulatory targets; FQD, Fuzheng Quxie Decoction.
Figure 3
Figure 3
PPI network of DRTs and PRTs. Notes: (A) PPI network with 32 DRTs as seeds. Pink nodes represent the 32 DRTs, blue nodes represent the proteins that have been reported to have interactions with the DRTs, and yellow nodes represent 245 PRTs with a DC value greater than twice the average. (B) PPI network of the 245 chosen PRTs, with nine DRTs (pink nodes). Abbreviations: DC, degree centrality; DRTs, direct regulatory targets; PPI, protein–protein interaction; PRTs, possible regulatory targets.
Figure 4
Figure 4
GO enrichment of 245 PRTs. Most significantly enriched terms are displayed. Abbreviations: GO, gene ontology; PRTs, possible regulatory targets.
Figure 5
Figure 5
The top-ten enriched pathways of the 245 PRTs analyzed by FunRich 3.0. Abbreviations: PRTs, possible regulatory targets; VEGF, vascular endothelial growth factor; VEGFR, VEGF-receptor.
Figure 6
Figure 6
Effect of Fuzheng Quxie Decoction (FQD) on spatial learning and memory ability of SAMP8 mice. Notes: (A) Ratio of time in platform quadrant to total swimming time; (B) ratio of swimming distance in platform quadrant to total swimming distance. (▲▲P<0.01 vs control group; *P<0.05, **P<0.01 vs model group; n=10).
Figure 7
Figure 7
Effect of Fuzheng Quxie Decoction (FQD) on memory-retention ability of SAMP8 mice. Notes: (A) Avoidance latency that mice spent to come into dark compartment for the first time; (B) error times in the dark compartment. (▲P<0.05, ▲▲P<0.01 vs control group; *P<0.05, **P<0.01 vs model group; n=10).
Figure 8
Figure 8
Effect of Fuzheng Quxie Decoction (FQD) on cerebrovascular morphology in the cortex of SAMP8 mice. Note: H&E staining, magnification 100× and 400×.
Figure 9
Figure 9
Effect of Fuzheng Quxie Decoction (FQD) on neuronal morphology in hippocampus CA1 region of SAMP8 mice. Note: Nissl staining, magnification 200×.
Figure 10
Figure 10
Effect of Fuzheng Quxie Decoction (FQD) on VEGF expression in brains of SAMP8 mice. Notes: (A) VEGF-positive cells in cortex by immunohistochemistry (magnification 400×); (B) quantification of VEGF-positive cells in cortex; (C) VEGF bands detected by Western blot analysis; (D) quantification of VEGF expression, normalized as ratio to β-actin. ▲▲P<0.01 vs control group; *P<0.05, **P<0.01 vs model group (B and D).
Figure 11
Figure 11
Effect of Fuzheng Quxie Decoction (FQD) on hypoxia-induced factor 1α (HIF1α) expression in brains of SAMP8 mice. Notes: (A) HIF1α bands detected by Western blot analysis; (B) shows the quantification of HIF1α expression normalized as the ratio to β-actin. (▲P<0.05 vs control group; *P<0.05, **P<0.01 vs model group; n=5).
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