Food-Derived Small Molecules for Brain Health: Structure-Based Target Discovery, Blood–Brain Barrier Penetration, and Mechanistic Validation

What we eat does more than fuel the body; it also supplies small molecules that can influence brain-related pathways. During digestion and metabolism, foods, especially plant-derived foods rich in secondary metabolites, yield a diverse set of compounds and derivatives that may enter circulation, undergo biotransformation, and in some cases achieve meaningful brain exposure. These metabolites can modulate proteins involved in neuroinflammation, oxidative stress, synaptic signaling, and neurovascular integrity, thereby shaping cognition, mood, and brain resilience across the lifespan. The goal of this Research Topic is to advance a molecule-to-mechanism understanding of nutrition and brain health by identifying which specific food-derived metabolites are bioavailable, which can plausibly reach the brain, and which molecular targets they engage. While many studies report associations between diets and neurological outcomes, the field still needs stronger mechanistic clarity: Which metabolites matter most? What are their targets? How strong and stable are these interactions? By integrating nutrition science with structure-based computational chemistry and experimental validation, this Topic aims to map diet-derived metabolites to actionable brain-relevant targets and pathways. This Research Topic welcomes studies that connect food-derived metabolites to brain health through structure–activity and target-based evidence. We particularly encourage submissions that use molecular docking, virtual screening, molecular dynamics simulations, and binding free-energy analyses, ideally paired with biochemical or cellular validation, to (i) identify likely targets, (ii) characterize binding modes and selectivity, and (iii) prioritize metabolites with plausible blood-brain barrier permeability or transport. Work on natural products and plant secondary metabolites (including cereal metabolites) and their biologically relevant derivatives is especially encouraged. We invite submissions of original research, systematic or narrative reviews, mini-reviews, brief reports, and perspectives. Interdisciplinary work bridging nutrition, metabolomics, cheminformatics, and mechanistic neuroscience is highly valued. This Topic aims to provide a focused platform for target-driven, mechanistic nutrition research that clarifies how diet-derived small molecules may support brain health and inform prevention-oriented strategies. Topic editors: Gourav Choudhir, Asimul Islam Source: https://www.frontiersin.org/research-topics/77127/food-derived-small-molecules-for-brain-health-structure-based-target-discovery-blood-brain-barrier-penetration-and-mechanistic-validation