title: Effects of a Standardized Phenolic-Enriched Maple Syrup Extract on β-Amyloid Aggregation, Neuroinflammation in Microglial and Neuronal Cells, and β-Amyloid Induced Neurotoxicity in Caenorhabditis elegans.
abstract: Published data supports the neuroprotective effects of several phenolic-containing natural products, including certain fruit, berries, spices, nuts, green tea, and olive oil. However, limited data are available for phenolic-containing plant-derived natural sweeteners including maple syrup. Herein, we investigated the neuroprotective effects of a chemically standardized phenolic-enriched maple syrup extract (MSX) using a combination of biophysical, in vitro, and in vivo studies. Based on biophysical data (Thioflavin T assay, transmission electron microscopy, circular dichroism, dynamic light scattering, and zeta potential), MSX reduced amyloid β1-42peptide (Aβ1-42) fibrillation in a concentration-dependent manner (50-500 μg/mL) with similar effects as the neuroprotective polyphenol, resveratrol, at its highest test concentration (63.5 % at 500 μg/mL vs. 77.3 % at 50 μg/mL, respectively). MSX (100 μg/mL) decreased H2O2-induced oxidative stress (16.1 % decrease in ROS levels compared to control), and down-regulated the production of lipopolysaccharide (LPS)-stimulated inflammatory markers (22.1, 19.9, 74.8, and 87.6 % decrease in NOS, IL-6, PGE2, and TNFα levels, respectively, compared to control) in murine BV-2 microglial cells. Moreover, in a non-contact co-culture cell model, differentiated human SH-SY5Y neuronal cells were exposed to conditioned media from BV-2 cells treated with MSX (100 μg/mL) and LPS or LPS alone. MSX-BV-2 media increased SH-SY5Y cell viability by 13.8 % compared to media collected from LPS-BV-2 treated cells. Also, MSX (10 μg/mL) showed protective effects against Aβ1-42induced neurotoxicity and paralysis in Caenorhabditis elegans in vivo. These data support the potential neuroprotective effects of MSX warranting further studies on this natural product.
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, 02881, USA.
authors.forename: Hang
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, 02881, USA.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: DaSilva
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, 02881, USA.
authors.forename: Weixi
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, 02881, USA.
authors.forename: Pragati P
authors.initials: PP
authors.lastname: Nahar
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, 02881, USA.
authors.forename: Zhengxi
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, 02881, USA.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Nutrition Biomedicine and Biotechnology, Texas State University, San Marcos, TX, 78666, USA.
authors.forename: Priscilla T
authors.initials: PT
authors.lastname: Pham
authors.affiliation: Nutrition Biomedicine and Biotechnology, Texas State University, San Marcos, TX, 78666, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Crews
authors.affiliation: Nutrition Biomedicine and Biotechnology, Texas State University, San Marcos, TX, 78666, USA.|School of Applied Health Sciences and Wellness, Grover Center E160A, Ohio University, Athens, OH, 45701, USA.
authors.forename: Dhiraj A
authors.initials: DA
authors.lastname: Vattem
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, 02881, USA.
authors.forename: Angela L
authors.initials: AL
authors.lastname: Slitt
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, 02881, USA.
authors.forename: Zahir A
authors.initials: ZA
authors.lastname: Shaikh
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, 02881, USA. nseeram@uri.edu.
authors.forename: Navindra P
authors.initials: NP
authors.lastname: Seeram
mesh_terms: D031002:Acer / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D017173:Caenorhabditis elegans; D002470:Cell Survival / Q000187:drug effects*; D018920:Coculture Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000378:metabolism; D020258:Neurotoxicity Syndromes / Q000378:metabolism*; D010636:Phenols / Q000494:pharmacology; D059808:Polyphenols
chemical_list: D016229:Amyloid beta-Peptides; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D010636:Phenols; D059808:Polyphenols
keywords: Alzheimer’s disease; Amyloid β1−42; Caenorhabditis elegans; Maple syrup phenolics; Neuroinflammation; Neuroprotective