KEY WORDS:berry anthocyanins; glycation; neuroprotection; beta amyloid; oxidative stress;Alzheimer’s disease

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1 School of Chemical and Environment Engineering, Wuyi University; International Healthcare Innovation
Institute (Jiangmen), Jiangmen 529020, Guangdong, China; hang_ma@uri.edu
2 Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences,
College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA; shelby_johnson@uri.edu (S.L.J.);
ndasilva@my.uri.edu (N.A.D.)
3 George and Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI 02881, USA
4 Department of Chemistry, University of Rhode Island, Kingston, RI 02881, USA;
weixi_liu@my.uri.edu (W.L.); jdain@chm.uri.edu (J.A.D.)
5 Department of Chemistry, Salve Regina University, Newport, RI 02840, USA; Susan.Meschwitz@salve.edu
* Correspondence: nseeram@uri.edu; Tel.: +1-401-874-9367

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ABSTRACT：Glycation is associated with several neurodegenerative disorders, including Alzheimer’s disease (AD), where it potentiates the aggregation and toxicity of proteins such as -amyloid (A). Published studies support the anti-glycation and neuroprotective effects of several polyphenol-rich fruits, including berries, which are rich in anthocyanins. Herein, blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry extracts were evaluated for: (1) total phenolic and anthocyanins contents, (2) free radical (DPPH) scavenging and reactive carbonyl species (methylglyoxal; MGO) trapping, (3) anti-glycation (using BSA-fructose and BSA-MGO models),
(4) anti-A aggregation (using thermal- and MGO-induced fibrillation models), and, (5) murine microglia (BV-2) neuroprotective properties. Berry crude extracts (CE) were fractionated to yield anthocyanins-free (ACF) and anthocyanins-enriched (ACE) extracts. The berry ACEs (at 100 g/mL) showed superior free radical scavenging, reactive carbonyl species trapping, and anti-glycation effects compared to their respective ACFs. The berry ACEs (at 100 g/mL) inhibited both thermaland MGO-induced A fibrillation. In addition, the berry ACEs (at 20 g/mL) reduced H2O2-induced reactive oxygen species production, and lipopolysaccharide-induced nitric oxide species in BV-2 microglia as well as decreased H2O2-induced cytotoxicity and caspase-3/7 activity in BV-2 microglia. The free radical scavenging, reactive carbonyl trapping, anti-glycation, anti-A fibrillation, and microglial neuroprotective effects of these berry extracts warrant further in vivo studies to evaluate their potential neuroprotective effects against AD.