Anti-neuroinflammatory effects of a food-grade phenolic-enriched maple syrup extract in a mouse model of Alzheimer’s disease

ABSTRACT

Objectives: Alzheimer's disease (AD) is a growing global health crisis exacerbated by increasing life span and an aging demographic. Convergent lines of evidence, including genome-wide association studies, strongly implicate neuroinflammation in the pathogenesis of AD. Several dietary agents, including phenolic-rich foods, show promise for the prevention and/or management of AD, which in large part, has been attributed to their anti-inflammatory effects. We previously reported that a food-grade phenolic-enriched maple syrup extract (MSX) inhibited neuroinflammation in vitro but whether these effects are translatable in vivo remain unknown. Herein, we assessed MSX's ability to attenuate early neuroinflammation in a transgenic mouse model of AD.

Methods: The effects of MSX on AD-related neuroinflammation was evaluated by orally administering MSX (100 and 200 mg/kg/day for 30 days) to the 3xTg-AD mouse model of AD. The expression of inflammatory markers in mouse brains were analyzed with LC-MS/MS with SWATH acquisition.

Results: 3xTg-AD mice dosed orally with MSX have decreased expression of several inflammatory proteins, including, most notably, the AD risk-associated protein ‘triggering receptor expressed on myeloid cells-2’ (TREM2), and stimulator of interferon genes TMEM173, and suppressor of cytokine signaling-6 (SOCS6). However, this decrease in inflammation did not coincide with a decrease in pathogenic amyloid generation or lipid peroxidation.

Discussion: These data demonstrate that oral administration of this maple syrup derived natural product reduces key neuroinflammatory indices of AD in the 3xTg-AD model of AD. Therefore, further studies to investigate MSX's potential as a dietary intervention strategy for AD prevention and/or management are warranted.

KEYWORDS:

• Maple syrup extract
• phenolics
• Alzheimer’s disease
• TREM2
• neuroinflammation

Acknowledgments

This projected was supported by the Quebec Maple Syrup Producers. The large-scale production of food-grade MSX was completed by Silicycle Inc. (Quebec, Canada). K.R. was supported by a fellowship from the George and Anne Ryan Institute for Neuroscience. Several instruments used for the completion of this study were located in RI-INBRE core facility supported by Grant # P20GM103430 from the National Institute of General Medical Sciences of the National Institutes of Health. The authors would like to thank Dr. Frank Menniti and Mark Majchrzak for their guidance of animal procedures.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This project was supported by the Quebec Maple Syrup Producers. The large-scale production of food-grade MSX was completed by Silicycle Inc. (Quebec, Canada). K.R. was supported by a fellowship from the George and Anne Ryan Institute for Neuroscience. Several instruments used for the completion of this study were located in RI-INBRE core facility supported by Grant # P20GM103430 from the National Institute of General Medical Sciences of the National Institutes of Health. The authors would like to thank Dr. Frank Menniti and Mark Majchrzak for their guidance of animal procedures.

Notes on contributors

Kenneth N. Rose

Kenneth N. Rose, Ph.D. received his doctoral degree from the University of Rhode Island in 2019. He is currently a postdoctoral research fellow at Harvard Medical School.

Benjamin J. Barlock

Benjamin J. Barlock is a doctoral student at the University of Rhode Island.

Nicholas A. DaSilva

Nicholas A. DaSilva, Ph.D. received his doctoral degree from the University of Rhode Island in 2019. He is currently a postdoctoral research fellow at the University of Rhode Island.

Shelby L. Johnson

Shelby L. Johnson is a doctoral student at the University of Rhode Island.

Chang Liu

Chang Liu is a doctoral student at the University of Rhode Island.

Hang Ma

Hang Ma, Ph.D. is a research associate at University of Rhode Island. Associate Director of Bioactive Botanical Research Laboratory at University of Rhode Island. His research interests include identification and biological evaluation of natural products from medicinal foods and plants.

Robert Nelson

Robert Nelson, Ph.D. is affiliated with MindImmune Therapeutics, Inc., a pharmaceutical company developing first-in-class drugs that target the immune system to treat diseases of the central nervous system. Dr. Nelson has over 24 years of experience in pharmaceutical drug discovery and development, including work on both small molecule and biologic drug candidates.

Fatemeh Akhlaghi

Fatemeh Akhlaghi, Ph.D. is a Professor & the Ernest Mario Distinguished Chair in Pharmaceutics of College of Pharmacy at the University of Rhode Island. Her research interests include (1) the effect of diabetes mellitus and Non-Alcoholic Fatty Liver disease (NAFLD) on drug metabolism and pharmacokinetics and (2) Drug development in alcohol use disorder.

Navindra P. Seeram

Navindra P. Seeram, Ph.D. is a Professor, and the Department Chair of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island. His research group, the Bioactive Botanical Research Laboratory, investigates medicinal plants and their derived natural products for preventive and therapeutic effects against chronic human diseases. Dr. Seeram has co-authored over 170 original peer-reviewed research articles, 9 review-type articles, 17 book chapters, and 7 international patents.