Anthocyanin-rich blueberry extracts and anthocyanin metabolite protocatechuic acid promote autophagy-lysosomal pathway and alleviate neurons damage in in vivo and in vitro models of Alzheimer's disease

As the global aging phenomenon intensifies, the incidence of Alzheimer's disease (AD) is gradually increasing. Diet appears to be an effective way to prevent and delay the progression of AD. 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. The aims of this study were to detect the main anthocyanins of BBE; then to verify the protective effects of anthocyanin-rich BBE on hippocampal neurons and the promotion of autophagy; and finally to investigate the main protective effects and mechanisms of protocatechuic acid (PCA), a major metabolite of BBE, for promoting autophagy and thus playing a neuroprotective role.APP/PS1 mice were given 150 mg/kg BBE daily for 16 wk. Morphology of neurons was observed and autophagy-related proteins were detected.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 neuron viability and increased levels of lactate dehydrogenase and reactive oxygen species, was effectively reversed by PCA. 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.