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 β1–42 peptide (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 Aβ1–42 induced neurotoxicity and paralysis in Caenorhabditis elegans in vivo. These data support the potential neuroprotective effects of MSX warranting further studies on this natural product.

Anti-glycation and anti-oxidative effects of a phenolic-enriched maple syrup extract and its protective effects on normal human colon cells

“…20 Moreover, MSX shows neuroprotective effects in Caennorhabditis elegans and alleviate lipopolysaccharide-induced inflammation and cell stress in murine microglial and human neuronal cells. 28 As previously discussed, AGEs could trigger cell stress by inducing oxidative stress and activating inflammatory signaling pathways. 43 Therefore, in the current study, we evaluated the protective effects of MSX against AGE-induced cytotoxicity on normal/non-tumorigenic colon CCD-18Co cells.…”

“…25 Therefore, we have taken a whole-food approach towards studying the biological effects of this botanical natural product as we reported in our recent evaluation of the neuroprotective effects of MSX. 28 With regards to the phenolic content of the extract, we have previously reported on the development of a maple product specific standard, named MaPLES (maple phenolic lignan-enriched standard), for the quantification of phenolic content of maple-derived food products since MSX contains predominantly lignans which cannot be adequately quantified based on gallic acid equivalents (GAEs). 35 Therefore, MSX contains 92.4% phenolic content based on MaPLES equivalents; see Supplementary Information Table S1).…”

“…Given the wide popularity and consumption of this sweetener, we initiated this study on MSX, a standardized food-grade phenolic-enriched maple syrup derived extract (previously developed by our group for nutraceutical applications), which contains the natural chemical composition of the whole maple syrup food but with reduced sucrose content. 20, 28 …”

“…More recently, our group has also reported on the neuroprotective effects of MSX on murine microglia BV-2 cells, human neuronal SH-SY5Y cells, and against neurotoxicity in Caenorhabditis elegans in vivo. 28 However, to date, there have been no anti-AGE related studies on this natural product.…”

Effect of dark-colored maple syrup on cell proliferation of human gastrointestinal cancer cell

“…Previous studies, some recent, reported that maple syrup also contains several phytochemicals, including phenolic compounds that present hypoglycemic, antioxidant, antimutagenic, anticancer, anti-inflammatory, antibiotic and anti-neurodegenerative effects (9–17). Moreover, biological effects have been noted following maple syrup consumption.…”