PRG ameliorates cognitive impairment in Alzheimer's disease mice by regulating β-amyloid and targeting the ERK pathway

Zhang，Zhiyuan1; Wu，Haoran2; Wang，Shuai1; Li，Yuanyuan1; Yang，Pei1; Xu，Lingchuan1; Liu，Yuhong1; Liu，Maoxuan3

2024-07-25

10.1016/j.phymed.2024.155671

Phytomedicine   影响因子和分区

0944-7113

1618-095X

Background: PRG is derived from Phellinus ribis and is a homogeneous polysaccharide with well-defined structural information. PRG was found to have significant in vitro neurotrophic and neuroprotective activities. Thus, PRG might be a potential treatment for Alzheimer's disease. However, the related mechanisms of action are still unclear, so deeper in vivo experimental validation and the potential mechanisms need to be investigated. Purpose: The effects of PRG on AD mice were investigated using Senescence-accelerated SAMP8 mice as an AD model to elucidate the crucial molecular mechanisms. Methods: PRG was obtained from Phellinus ribis by water-alcohol precipitation, column chromatography, and ultrafiltration. The Morris water maze and novel object recognition behavioral assays were used to evaluate the effects of PRG in AD mice. Nissl staining, the TUNEL apoptosis assay, and Golgi staining were used to assess brain neuronal cell damage, apoptosis, and neuronal status. Enzyme-linked immunosorbent assays, Western blotting, and immunofluorescence were used to explore the impacts of correlated factors and protein pathways under relevant mechanisms. Results: The findings suggest that PRG improved learning ability and spatial memory capacity in SAMP8 mice. PRG hastened the disintegration of β-amyloid, reduced the content and abnormal accumulation of the toxic Aβ protein, and decreased apoptosis. PRG activated the BDNF/ERK/CREB signaling pathway through a cascade, exerted neurotrophic effects, regulated cell proliferation and differentiation, increased neuronal dendritic branching and spine density, and improved synaptic plasticity. Conclusion: PRG promoted β-amyloid degradation to reduce neuronal damage and apoptosis. It exerted neurotrophic effects by activating the BDNF/ERK/CREB pathway, promoting neuronal dendritic branching and dendritic spine growth, regulating cell proliferation and differentiation, and improving synaptic plasticity, which improved AD. Taken together, as a novel natural active polysaccharide with a well-defined structure, PRG affected AD symptoms in senescence-accelerated mice by interacting with multiple targets. The results indicate that PRG is a promising potential anti-AD drug candidate.

Alzheimer's disease Aβ1–42 Neuronutrition Phellinus ribis PRG SAMP8 mice

SCI

英语

其他

PHARMACOLOGY & TOXICOLOGY

2-s2.0-85193440367

Scopus

1.School of Pharmaceutical Sciences,Shandong University of Traditional Chinese Medicine,Jinan,250355,China
2.School of Medicine,Southern University of Science and Technology,Shenzhen,518055,China
3.Center for Protein and Cell-Based Drugs,Institute of Biomedicine and Biotechnology,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen,518055,China

Zhang，Zhiyuan,Wu，Haoran,Wang，Shuai,et al. PRG ameliorates cognitive impairment in Alzheimer's disease mice by regulating β-amyloid and targeting the ERK pathway[J]. Phytomedicine,2024,130.

Zhang，Zhiyuan.,Wu，Haoran.,Wang，Shuai.,Li，Yuanyuan.,Yang，Pei.,...&Liu，Maoxuan.(2024).PRG ameliorates cognitive impairment in Alzheimer's disease mice by regulating β-amyloid and targeting the ERK pathway.Phytomedicine,130.

Zhang，Zhiyuan,et al."PRG ameliorates cognitive impairment in Alzheimer's disease mice by regulating β-amyloid and targeting the ERK pathway".Phytomedicine 130(2024).