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Recommendations for Development of Botanical Polyphenols as “Natural Drugs” for Promotion of Resilience Against Stress-Induced Depression and Cognitive Impairment

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Abstract

Extensive evidence has demonstrated that psychological stress has detrimental effects on psychological health, cognitive function, and ultimately well-being. While stressful events are a significant cause of psychopathology, most individuals exposed to adversity maintain normal psychological functioning. The mechanisms underlying such resilience are poorly understood, and there is an urgent need to identify and target these mechanisms to promote resilience under stressful events. Botanicals have been used throughout history to treat various medical conditions; however, the development of botanical compounds into potential preventative and therapeutic agents in studies promoting brain health is hindered by the fact that most orally consumed botanicals are extensively metabolized during absorption and/or by post-absorptive xenobiotic metabolism. Therefore, the primary objective of this review article is to provide recommendations for developing natural compounds as novel therapeutic strategies to promote resilience in susceptible subjects. The development of botanical polyphenols to ultimately attenuate mood disorders and cognitive impairment will rely on understanding (1) the absorption and bioavailability of botanical polyphenols with emphasis on flavan-3-ols, (2) the characterization of tissue-specific accumulation of biologically available polyphenols and their mechanisms of action in the brain, and eventually (3) the characterization of biologically available polyphenol metabolites in mechanisms associated with the promotion of resilience against mood disorders and cognitive impairment in response to stress. We also summarize exciting new lines of investigation about the role of botanicals such as polyphenols in the promotion of cognitive and psychological resilience. This information will provide a strategical framework for the future development of botanicals as therapeutic agents to promote resilience, ultimately preventing and/or therapeutically treating cognitive impairment and psychological dysfunction.

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Acknowledgments

This publication was supported by Grant Number P50 AT008661-01, titled “Dietary Botanicals in the Preservation of Cognitive and Psychological Resilience,” from the National Center for Complementary and Integrative Health (NCCIH) and the Office of Dietary Supplements (ODS). In addition, Dr. Pasinetti holds a Career Scientist Award in the Research and Development unit and is the Director of the Basic and Biomedical Research and Training Program, GRECC, James J. Peters Veterans Affairs Medical Center. We acknowledge that the contents of this manuscript do not represent the views of the NCCIH, ODS, National Institutes of Health, U.S. Department of Veterans Affairs, or the United States Government.

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  1. Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA

    Libby Ward & Giulio Maria Pasinetti

  2. Geriatric Research Education and Clinical Center, James J. Peters Veterans Affairs Medical Center, Bronx, NY, 10468, USA

    Giulio Maria Pasinetti

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  1. Libby Ward
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Correspondence to Giulio Maria Pasinetti.

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Ward, L., Pasinetti, G.M. Recommendations for Development of Botanical Polyphenols as “Natural Drugs” for Promotion of Resilience Against Stress-Induced Depression and Cognitive Impairment. Neuromol Med 18, 487–495 (2016). https://doi.org/10.1007/s12017-016-8418-6

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