Qingyangshen mitigates amyloid-β and Tau aggregate defects involving PPARα-TFEB activation in transgenic mice of Alzheimer's disease

Background: Alzheimer's disease (AD) is the most common neurodegenerative disease. Deposition of amyloid beta plaques (A beta) and neurofibrillary tangles (NFTs) is the key pathological hallmark of AD. Accumulating evidence suggest that impairment of autophagy-lysosomal pathway (ALP) plays key roles in AD pathology. Purpose: The present study aims to assess the neuroprotective effects of Qingyangshen (QYS), a Chinese herbal medicine, in AD cellular and animal models and to determine its underlying mechanisms involving ALP regulation. Methods: QYS extract was prepared and its chemical components were characterized by LC/MS. Then the pharmacokinetics and acute toxicity of QYS extract were evaluated. The neuroprotective effects of QYS extract were determined in 3XTg AD mice, by using a series of behavioral tests and biochemical assays, and the mechanisms were examined in vitro. Results: Oral administration of QYS extract improved learning and spatial memory, reduced carboxy-terminal fragments (CTFs), amyloid precursor protein (APP), A beta and Tau aggregates, and inhibited microgliosis and astrocytosis in the brains of 3XTg mice. Mechanistically, QYS extract increased the expression of PPAR alpha and TFEB, and promoted ALP both in vivo and in vitro. Conclusion: QYS attenuates AD pathology, and improves cognitive function in 3XTg mice, which may be mediated by activation of PPAR alpha-TFEB pathway and the subsequent ALP enhancement. Therefore, QYS may be a promising herbal material for further anti-AD drug discovery.

Automated summary

The study demonstrated that QYS extract improved cognitive function and attenuated AD pathology in 3XTg mice by promoting the expression of PPAR alpha and TFEB, and enhancing ALP both in vivo and in vitro.