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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Abd El Mohsen, M. M., Kuhnle, G., Rechner, A. R., Schroeter, H., Rose, S., Jenner, P., et al. (2002). Uptake and metabolism of epicatechin and its access to the brain after oral ingestion. Free Radical Biology and Medicine, 33, 1693–1702.
Abd El-Mohsen, M., Bayele, H., Kuhnle, G., Gibson, G., Debnam, E., Kaila, S. S., et al. (2006). Distribution of [3H]trans-resveratrol in rat tissues following oral administration. British Journal of Nutrition, 96, 62–70.
Aburn, G., Gott, M., & Hoare, K. (2016). What is resilience? An integrative review of the empirical literature. Journal of Advanced Nursing, 72, 980–1000.
Association, A. P. (2013). Diagnostic and statistical manual of mental disorders. Arlington: American Psychiatric Publishing.
Aura, A. M., Mattila, I., Seppanen-Laakso, T., Miettinen, J., Oksman-Caldentey, K. M., & Oresic, M. (2008). Microbial metabolism of catechin stereoisomers by human faecal microbiota: comparison of targeted analysis and a non-targeted metabolomics method. Phytochemistry Letters, 1, 18–22.
Aura, A. M., O’Leary, K. A., Williamson, G., Ojala, M., Bailey, M., Puupponen-Pimia, R., et al. (2002). Quercetin derivatives are deconjugated and converted to hydroxyphenylacetic acids but not methylated by human fecal flora in vitro. Journal of Agriculture and Food Chemistry, 50, 1725–1730.
Bolca, S., Van de, W. T., & Possemiers, S. (2013). Gut metabotypes govern health effects of dietary polyphenols. Current Opinion in Biotechnology, 24, 220–225.
Calani, L., Dall’Asta, M., Derlindati, E., Scazzina, F., Bruni, R., & Del, R. D. (2012). Colonic metabolism of polyphenols from coffee, green tea, and hazelnut skins. Journal of Clinical Gastroenterology, 46(Suppl), S95–S99.
Chen, A. Y., & Chen, Y. C. (2013). A review of the dietary flavonoid, kaempferol on human health and cancer chemoprevention. Food Chemistry, 138, 2099–2107.
Chen, H., Hayek, S., Rivera, G. J., Gillitt, N. D., Ibrahim, S. A., Jobin, C., et al. (2012). The microbiota is essential for the generation of black tea theaflavins-derived metabolites. PLoS One, 7, e51001.
Chen, T. Y., Kritchevsky, J., Hargett, K., Feller, K., Klobusnik, R., Song, B. J., et al. (2015). Plasma bioavailability and regional brain distribution of polyphenols from apple/grape seed and bilberry extracts in a young swine model. Molecular Nutrition and Food Research, 59, 2432–2447.
Colten, H. R., Altevogt, B. M., & Institute of Medicine (and Committee on Sleep Medicine and Research). (2006). Sleep disorders and sleep deprivation an unmet public health problem. Institute of Medicine: Washington, DC.
Dowlati, Y., Herrmann, N., Swardfager, W., Liu, H., Sham, L., Reim, E. K., et al. (2010). A meta-analysis of cytokines in major depression. Biological Psychiatry, 67, 446–457.
Farzaei, M. H., Bahramsoltani, R., Rahimi, R., Abbasabadi, F., & Abdollahi, M. (2016). A systematic review of plant-derived natural compounds for anxiety disorders. Current Topics in Medicinal Chemistry, 16, 1924–1942.
Ferruzzi, M. G., Lobo, J. K., Janle, E. M., Cooper, B., Simon, J. E., Wu, Q. L., et al. (2009). Bioavailability of gallic acid and catechins from grape seed polyphenol extract is improved by repeated dosing in rats: implications for treatment in Alzheimer’s disease. Journal of Alzheimer’s Disease, 18, 113–124.
Ford, D. E., & Kamerow, D. B. (1989). Epidemiologic study of sleep disturbances and psychiatric disorders. An opportunity for prevention? JAMA, 262, 1479–1484.
Gasperotti, M., Passamonti, S., Tramer, F., Masuero, D., Guella, G., Mattivi, F., et al. (2015). Fate of microbial metabolites of dietary polyphenols in rats: Is the brain their target destination? ACS. Chemical Neuroscience, 6, 1341–1352.
Gillin, J. C. (1998). Are sleep disturbances risk factors for anxiety, depressive and addictive disorders? Acta Psychiatrica Scandinavica. Supplementum, 393, 39–43.
Goel, N., Rao, H., Durmer, J. S., & Dinges, D. F. (2009). Neurocognitive consequences of sleep deprivation. Seminars in Neurology, 29, 320–339.
Hirotsu, C., Tufik, S., Bergamaschi, C. T., Tenorio, N. M., Araujo, P., & Andersen, M. L. (2010). Sleep pattern in an experimental model of chronic kidney disease. American Journal of Physiology—Renal Physiology, 299, F1379–F1388.
Ho, L., Ferruzzi, M. G., Janle, E. M., Wang, J., Gong, B., Chen, T. Y., et al. (2013). Identification of brain-targeted bioactive dietary quercetin-3-O-glucuronide as a novel intervention for Alzheimer’s disease. FASEB Journal, 27, 769–781.
Jiang, F., Chang, C. W., & Dusting, G. J. (2010). Cytoprotection by natural and synthetic polyphenols in the heart: novel mechanisms and perspectives. Current Pharmaceutical Design, 16, 4103–4112.
Kamphuis, J., Meerlo, P., Koolhaas, J. M., & Lancel, M. (2012). Poor sleep as a potential causal factor in aggression and violence. Sleep Medicine, 13, 327–334.
Kapur, V. K., Redline, S., Nieto, F. J., Young, T. B., Newman, A. B., & Henderson, J. A. (2002). The relationship between chronically disrupted sleep and healthcare use. Sleep, 25, 289–296.
Kiani, B. H., Suberu, J., & Mirza, B. (2016). Cellular engineering of Artemisia annua and Artemisia dubia with the rol ABC genes for enhanced production of potent anti-malarial drug artemisinin. Malar Journal, 15, 252.
Kimhi, S. (2016). Levels of resilience: Associations among individual, community, and national resilience. Journal of Health Psychology, 21, 164–170.
Kinrys, G., Coleman, E., & Rothstein, E. (2009). Natural remedies for anxiety disorders: potential use and clinical applications. Depression and Anxiety, 26, 259–265.
Knutson, K. L., & Van, C. E. (2008). Associations between sleep loss and increased risk of obesity and diabetes. Annals of the New York Academy of Sciences, 1129, 287–304.
Kreutzer, J. S., Marwitz, J. H., Sima, A. P., Bergquist, T. F., Johnson-Greene, D., Felix, E. R., et al. (2016). Resilience following traumatic brain injury: A traumatic brain injury model systems study. Archives of Physical Medicine and Rehabilitation, 97, 708–713.
Krikorian, R., Nash, T. A., Shidler, M. D., Shukitt-Hale, B., & Joseph, J. A. (2010). Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment. British Journal of Nutrition, 103, 730–734.
Krishnan, V., & Nestler, E. J. (2008). The molecular neurobiology of depression. Nature, 455, 894–902.
Lanquillon, S., Krieg, J. C., Bening-Abu-Shach, U., & Vedder, H. (2000). Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology, 22, 370–379.
Maes, M., Bosmans, E., De, J. R., Kenis, G., Vandoolaeghe, E., & Neels, H. (1997). Increased serum IL-6 and IL-1 receptor antagonist concentrations in major depression and treatment resistant depression. Cytokine, 9, 853–858.
Maes, M., Kubera, M., Obuchowiczwa, E., Goehler, L., & Brzeszcz, J. (2011). Depression’s multiple comorbidities explained by (neuro)inflammatory and oxidative and nitrosative stress pathways. Neuro Endocrinology Letters, 32, 7–24.
Maes, M., Van der, P. M., Stevens, W. J., Peeters, D., DeClerck, L. S., Bridts, C. H., et al. (1992). Leukocytosis, monocytosis and neutrophilia: hallmarks of severe depression. Journal of Psychiatric Research, 26, 125–134.
Margalef, M., Pons, Z., Iglesias-Carres, L., Arola, L., Muguerza, B., & Arola-Arnal, A. (2016). Gender related similarities and differences in the body distribution of grape seed flavanols in rats. Molecular Nutrition and Food Research, 60, 760–772.
Milbury, P. E., & Kalt, W. (2010). Xenobiotic metabolism and berry flavonoid transport across the blood-brain barrier. Journal of Agriculture and Food Chemistry, 58, 3950–3956.
Miller, A. H., Maletic, V., & Raison, C. L. (2009). Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biological Psychiatry, 65, 732–741.
Monagas, M., Urpi-Sarda, M., Sanchez-Patan, F., Llorach, R., Garrido, I., Gomez-Cordoves, C., et al. (2010). Insights into the metabolism and microbial biotransformation of dietary flavan-3-ols and the bioactivity of their metabolites. Food and Function, 1, 233–253.
Najafian, J., Mohamadifard, N., Siadat, Z. D., Sadri, G., & Rahmati, M. R. (2013). Association between sleep duration and diabetes mellitus: Isfahan Healthy Heart Program. Nigerian Journal of Clinical Practice, 16, 59–62.
Newman, D. J., & Cragg, G. M. (2012). Natural products as sources of new drugs over the 30 years from 1981 to 2010. Journal of Natural Products, 75, 311–335.
Ozdal, T., Sela, D. A., Xiao, J., Boyacioglu, D., Chen, F., & Capanoglu, E. (2016). The reciprocal interactions between polyphenols and gut microbiota and effects on bioaccessibility. Nutrients, 8(2), 78.
Palagini, L., Bruno, R. M., Gemignani, A., Baglioni, C., Ghiadoni, L., & Riemann, D. (2013). Sleep loss and hypertension: a systematic review. Current Pharmaceutical Design, 19, 2409–2419.
Pasinetti, G. M. (2012). Novel role of red wine-derived polyphenols in the prevention of Alzheimer’s disease dementia and brain pathology: Experimental approaches and clinical implications. Planta Medica, 78, 1614–1619.
Prasain, J. K., Peng, N., Dai, Y., Moore, R., Arabshahi, A., Wilson, L., et al. (2009). Liquid chromatography tandem mass spectrometry identification of proanthocyanidins in rat plasma after oral administration of grape seed extract. Phytomedicine, 16, 233–243.
Qureshi, N. A., & Al-Bedah, A. M. (2013). Mood disorders and complementary and alternative medicine: A literature review. Neuropsychiatric Disease and Treatment, 9, 639–658.
Rajaratnam, S. M. (2001). Legal issues in accidents caused by sleepiness. Journal of Human Ergology (Tokyo), 30, 107–111.
Rechner, A. R., Smith, M. A., Kuhnle, G., Gibson, G. R., Debnam, E. S., Srai, S. K., et al. (2004). Colonic metabolism of dietary polyphenols: Influence of structure on microbial fermentation products. Free Radical Biology and Medicine, 36, 212–225.
Rush, A. J., Warden, D., Wisniewski, S. R., Fava, M., Trivedi, M. H., Gaynes, B. N., et al. (2009). STAR*D: Revising conventional wisdom. CNS Drugs, 23, 627–647.
Russo, S. J., Murrough, J. W., Han, M. H., Charney, D. S., & Nestler, E. J. (2012). Neurobiology of resilience. Nature Neuroscience, 15, 1475–1484.
Schmidt, B., Ribnicky, D. M., Poulev, A., Logendra, S., Cefalu, W. T., & Raskin, I. (2008). A natural history of botanical therapeutics. Metabolism, 57, S3–S9.
Selma, M. V., Espin, J. C., & Tomas-Barberan, F. A. (2009). Interaction between phenolics and gut microbiota: role in human health. Journal of Agriculture and Food Chemistry, 57, 6485–6501.
Spencer, J. P. (2009). The impact of flavonoids on memory: physiological and molecular considerations. Chemical Society Reviews, 38, 1152–1161.
Van Dongen, H. P., Maislin, G., Mullington, J. M., & Dinges, D. F. (2003). The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation. Sleep, 26, 117–126.
Vijayan, V. K. (2012). Morbidities associated with obstructive sleep apnea. Expert Review of Respiratory Medicine, 6, 557–566.
Wang, J., Ho, L., Zhao, W., Ono, K., Rosensweig, C., & Chen, L. (2008). Grape-derived polyphenolics prevent Abeta oligomerization and attenuate cognitive deterioration in a mouse model of Alzheimer’s disease. Journal of Neuroscience, 28, 6388–6392.
Wang, D., Xia, M., Yan, X., Li, D., Wang, L., Xu, Y., et al. (2012a). Gut microbiota metabolism of anthocyanin promotes reverse cholesterol transport in mice via repressing miRNA-10b. Circulation Research, 111, 967–981.
Wang, J., Ferruzzi, M. G., Ho, L., Blount, J., Janle, E. M., Gong, B., et al. (2012b). Brain-targeted proanthocyanidin metabolites for Alzheimer’s disease treatment. Journal of Neuroscience, 32, 5144–5150.
Wang, D., Ho, L., Faith, J., Ono, K., Janle, E. M., Lachcik, P. J., et al. (2015). Role of intestinal microbiota in the generation of polyphenol-derived phenolic acid mediated attenuation of Alzheimer’s disease beta-amyloid oligomerization. Molecular Nutrition and Food Research, 59, 1025–1040.
Ward, N. C., Croft, K. D., Puddey, I. B., & Hodgson, J. M. (2004). Supplementation with grape seed polyphenols results in increased urinary excretion of 3-hydroxyphenylpropionic acid, an important metabolite of proanthocyanidins in humans. Journal of Agriculture and Food Chemistry, 52, 5545–5549.
Wollen, K. A. (2010). Alzheimer’s disease: The pros and cons of pharmaceutical, nutritional, botanical, and stimulatory therapies, with a discussion of treatment strategies from the perspective of patients and practitioners. Alternative Medicine Review, 15, 223–244.
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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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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DOI: https://doi.org/10.1007/s12017-016-8418-6