Anthocyanin-rich Blueberry Extracts and Anthocyanin Metabolite Protocatechuic Acid promote Autophagy-lysosomal Pathway and alleviate Neurons Damage in vivo and in vitro Models of Alzheimer's Disease

Abstract As the global aging phenomenon intensifies, the incidence of Alzheimer's disease (AD) is gradually increasing. It is an effective way to prevent and delay the progression of AD through diet. Previous studies have found that cognitive impairment and neuronal damage were effectively alleviated by blueberry extract (BBE) in AD mice, but its mechanism is still unclear. In this study, after administrated with BBE (150mg/kg/d) for 16 weeks in APP/PS1 mice, morphology of neurons was observed, and autophagy-related proteins were detected. Results showed that neuron damage in morphology was reduced and the expression of autophagy-related proteins in APP/PS1 mice were promoted after BBE treatment. In vitro, Aβ25-35-induced cytotoxicity, including decreased neurons viability and increased LDH and ROS levels, was effectively reversed by protocatechuic acid (PCA), the main metabolite of BBE. Furthermore, by adding autophagy inducers rapamycin and autophagy inhibitors Bafilomycin A1, it was verified that degradation of autophagosomes was upregulated and autophagy was promoted by PCA. This study elucidated the mechanism of BBE for reducing neuronal damage by promoting neuronal autophagy and proved PCA may be the main bioactive metabolite of BBE for neuroprotective effects, providing a basis for dietary intervention in AD.