Physiological and Cellular Targets of Neurotrophic Anxiolytic Phytochemicals in Food and Dietary Supplements

Abstract

Diet impacts anxiety in two main ways. First anxiety can be caused by deficiencies in antioxidants, neurotransmitter precursors, amino acids, cations and vitamins and other cofactors. Second, anxiety can be reduced by anxiolytic nutraceuticals which are food molecules that bind to molecular targets of the amygdala and the hypothalamus-pituitary–adrenal axis (HPA-axis). Anxiety is a feeling of fear that arises from a perceived threat and can be a beneficial coping mechanism to threats and stressors. However excessive anxiety is a disorder that interferes with healthy responses to stressors. The amygdala is responsible for assigning value to a threat or stressor and triggering the HPA-axis to support the body wide system responses to the threat. The amygdala also communicates with the neuroplastic learning and memory centers of the hippocampus to fix or set a learned value to the threat. Interestingly, many anxiolytic nutraceuticals that show benefits in human clinical trials have neurotrophic activity and increase neuronal plasticity. Moreover, anxiolytic nutraceuticals either act like the neurotrophins, nerve growth factor (NGF), brain derived neurotrophic factor (BDNF and neurotrophin-3 (NT3) by either directly binding to or potentiating the tyrosine receptor kinase (TRK) family of receptors (TRKA, TRKB and TRKC) and activating the ERK1/2 signal transduction pathway associated with neurite outgrowth and neural plasticity. This chapter will explore the neuritogenic activity of clinically proven plant-based anxiolytic nutraceuticals and examine the commonality of TRKA-C receptors and the ERK1/2 signaling pathway in the pharmacological and nutraceutical treatment of anxiety disorders.