Brain Neurotrophins and Plant Polyphenols: A Powerful Connection

Neurodegenerative disorders, mental conditions, and cognitive decline represent significant challenges worldwide, with growing pieces of evidence implicating alterations in neurotrophin signaling as central to these diseases. Neurotrophins-such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF)-are indispensable for neuronal survival, differentiation, and synaptic plasticity, and their dysregulation is closely associated with various neuropathological situations. Similarly, dietary plant polyphenols, abundant in vegetables, fruits, wine, tea, and extra virgin olive oil, show powerful anti-inflammatory, antioxidant, and anti-apoptotic activities. This narrative review critically addresses the evolving body of evidence that links plant polyphenols and brain neurotrophins, emphasizing several molecular mechanisms by which polyphenols regulate and modulate neurotrophin signaling. Crucial pathways include mitigation of neuroinflammatory responses, activation of intracellular cascades such as the cAMP response element-binding protein (CREB), epigenetic modulation, and the diminution of oxidative stress. Together, these effects contribute to potentiated enhanced synaptic function, neuronal integrity, and better learning and memory processes. Moreover, this narrative review examines how polyphenol-induced upregulation of neurotrophins may alleviate conditions associated not only with neurodegeneration but also with addiction and mood disorders, suggesting extensive therapeutic approaches. Findings from clinical investigations and animal models are presented to sustain the neuroprotective role of polyphenol-rich diets. Lastly, future research directions are recommended, focusing on polyphenol bioavailability optimization, considering combinatory dietary stratagems, and proposing personalized nutritional interventions. This wide-ranging perspective highlights plant polyphenols as encouraging modulators of neurotrophin pathways and supports their inclusion in approaches aimed at promoting brain health and counteracting neurodegenerative decline.