We recently identified, in preclinical studies, specific polyphenol-rich botanical dietary supplements [e.g., grape seed polyphenol extract (GSPE), Concord grape juice (CGJ), and resveratrol (RSV)] that are effective in promoting cognitive and psychological resilience under stress conditions. The overall goal of the proposed Botanical Dietary Supplement Research Center (BDSRC) is to identify the specific polyphenol components from these bioactive botanical supplements that underlie their bioactivities and to characterize specific cellular/molecular mechanisms contributing to the attenuation of physiological stress, such as that associated to stressful life events, that have detrimental impact on psychological health, cognitive functions, and ultimately wellbeing (Projects 1-2). In addition the proposed studies will, for the first time, clarify the role of the gastrointestinal (G) microbiome, particularly the human GI microbiome, in modulating the bioavailability of polyphenol components responsible for the cognitive and psychological health benefits of dietary polyphenol botanical supplements using humanized gnotobiotic mice (Project 3). Thus, the proposed studies, which (1) characterize botanicals, (2) assess, pre-clinically, their bioavailability and bioactivity in the periphery and in the brain, while defining molecular mechanisms of resilience, and (3) identify safety issues essential for future development into clinical application, are in full alignment with the goals of NCCAM and ODS, as indicated in the Research Objectives of the RFA. The proposed studies in this BDSRC will improve scientific knowledge and technical capabilities through the development of a rigorous scientific program, will provide training and career development opportunities, and, critically, will provide an intellectually rigorous examination of the role of dietary polyphenol botanical supplements in the maintenance and promotion of psychological and cognitive resilience.

Public Health Relevance

Promoting psychological and cognitive resilience in response to external stressors is one of the most difficult challenges to brain wellness. The proposed research in this BDSRC will provide a unique and detailed dissection of the role of dietary polyphenolic botanical supplements in the maintenance and promotion of psychological and cognitive resilience in models of social defeat and sleep deprivation.

National Institute of Health (NIH)
National Center for Complementary & Alternative Medicine (NCCAM)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZAT1)
Program Officer
Hopp, Craig
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Icahn School of Medicine at Mount Sinai
Schools of Medicine
New York
United States
Zip Code
Blaze, Jennifer; Wang, Jun; Ho, Lap et al. (2018) Polyphenolic Compounds Alter Stress-Induced Patterns of Global DNA Methylation in Brain and Blood. Mol Nutr Food Res 62:e1700722
Pfau, Madeline L; Ménard, Caroline; Russo, Scott J (2018) Inflammatory Mediators in Mood Disorders: Therapeutic Opportunities. Annu Rev Pharmacol Toxicol 58:411-428
Aleyasin, Hossein; Flanigan, Meghan E; Golden, Sam A et al. (2018) Cell-Type-Specific Role of ?FosB in Nucleus Accumbens In Modulating Intermale Aggression. J Neurosci 38:5913-5924
Aleyasin, Hossein; Flanigan, Meghan E; Russo, Scott J (2018) Neurocircuitry of aggression and aggression seeking behavior: nose poking into brain circuitry controlling aggression. Curr Opin Neurobiol 49:184-191
Ho, Lap; Cheng, Haoxiang; Wang, Jun et al. (2018) A Comprehensive Database and Analysis Framework To Incorporate Multiscale Data Types and Enable Integrated Analysis of Bioactive Polyphenols. Mol Pharm 15:840-850
Takahashi, Aki; Flanigan, Meghan E; McEwen, Bruce S et al. (2018) Aggression, Social Stress, and the Immune System in Humans and Animal Models. Front Behav Neurosci 12:56
Ho, Lap; Zhao, Danyue; Ono, Kenjiro et al. (2018) Heterogeneity in gut microbiota drive polyphenol metabolism that influences ?-synuclein misfolding and toxicity. J Nutr Biochem 64:170-181
Frolinger, Tal; Herman, Francis; Sharma, Ali et al. (2018) Epigenetic modifications by polyphenolic compounds alter gene expression in the hippocampus. Biol Open 7:
Evashwick-Rogler, Thomas W; Lai, Alon; Watanabe, Hironobu et al. (2018) Inhibiting tumor necrosis factor-alpha at time of induced intervertebral disc injury limits long-term pain and degeneration in a rat model. JOR Spine 1:
Frolinger, Tal; Smith, Chad; Cobo, Carmen Freire et al. (2018) Dietary polyphenols promote resilience against sleep deprivation-induced cognitive impairment by activating protein translation. FASEB J 32:5390-5404

Showing the most recent 10 out of 36 publications