Fuzheng Quxie Decoction Ameliorates Learning and Memory Impairment in SAMP8 Mice by Decreasing Tau Hyperphosphorylation

Abstract

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.

RETRACTED: Yizhi Qingxin Formula Extract Ameliorates Cognitive Decline in Aged Rats via the Brain-Derived Neurotrophic Factor/Tropomyosin Receptor Kinase B Pathway

“…In the central nervous system, cognitive impairment and decline in old age are primarily driven by the accumulation of age-related neuropathologies, and old age is thus the primary risk factor for neurodegenerative diseases such as AD (Boyle et al, 2017). Previous studies have shown that YQF extract significantly ameliorates cognitive impairment and protects cerebrovascular function in SAMP8 and APP/PS1 mice (Yang et al, 2017;Wang et al, 2018;Yang et al, 2019). Moreover, the main active ingredients of YQF extract were detected by liquid chromatography tandem mass spectrometry (LC-MS/MS), and alkaloids like berberine, palmatine, worenine, and protopine, and ginsenosides like Rg1, Re, Rb1, Rd, and Rc were found in plasma, while berberine, palmatine, epiberberine, coptisine, and ginsenoside Rb1 were found in brain tissue (Yang et al, 2019).…”

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

“…There was 3.71 g of crude drug per gram of the extract. Components were detected by HPLC as described by Yang et al 24 Memantine was obtained from the National Institute for Food and Drug Control (batch number H20120268; Beijing, China), produced by Lundbeck (Copenhagen, Denmark). When used, the extract and memantine were dissolved separately in distilled water at intended concentrations.…”

“…Our previous study indicated that FQD was able to reduce tau hyperphosphorylation, 24 but the underlying mechanistic basis was not determined. Therefore, in this study, active components of FQD were screened and possible targets and regulatory pathways predicted by network pharmacology.…”

“…Qi deficiency, blood stasis, and toxins can be respectively interpreted into modern concepts of aging symptoms, hyperlipemia, and Aβ and tau-protein deposition. Accumulating data have demonstrated that medicinal Chinese herbs or herbal formulas, such as Radix Ginseng , 14 , 15 Rhizoma Ligustici Chuanxiong , Rhizoma Coptidis , 16 , 17 Qifu Yin , 18 and Huannao Yicong Decoction, 19 – 22 tonify qi, dissolve blood stasis, and remove toxins to delay onset and progression of AD, and these have been widely used in clinics to treat AD in China.…”

“…FQD has been shown to alleviate AD symptoms and slow disease progression. 16 The constitutive herbs of FQD are Radix Ginseng , Rhizoma Ligustici Chuanxiong , and Rhizoma Coptidis and are used in different TCM areas. FQD has been used widely in clinics to treat AD in China.…”