From diet to brain repair: natural bioactive compounds in post-ischemic stroke recovery.

Abstract

Stroke represents the leading cause of disability and mortality worldwide, often resulting in long-term neurological deficits, extensive neuronal damage and inflammatory cascades. Ischemic stroke, which accounts for about 80% of stroke cases, is characterized by the sudden loss of blood circulation to an area of the brain, resulting in a corresponding loss of neurologic function. The blood supply interruption induced oxidative stress, mitochondrial dysfunction, neuroinflammation, and gut dysbiosis are involved in complex interactions within brain tissues. Moreover, the reperfusion induced inflammation produces more severe damage compared to the blood supply interruption. Current therapeutic interventions face critical limitations including narrow treatment windows, restricted patient eligibility, and significant adverse effects, underscoring the urgent need for safe, effective adjunctive strategies applicable during extended recovery periods. Recent research highlights the potential of nature biologically active substances, here we referred to food-derived and natural bioactive compounds, as promising therapeutic agents for post-stroke recovery. Administration of these compound by dietary route has the potential to support cellular repair processes via reducing oxidative stress, modulating neuroinflammation, promoting neurogenesis, inhibiting ferroptosis, and enhancing synaptic plasticity. This review examines the current evidence and emerging concepts on the roles of these bioactive compounds in post-stroke recovery and synthesizing mechanistic evidence. We discussed specific dietary sources and pharmacokinetics of selected compounds, providing insights into their bioavailability and potential synergistic effects with conventional therapies. Additionally, we examined clinical studies and evaluated the efficacy and safety of these interventions, offering a translational perspective on their integration into post-stroke rehabilitation. These findings underscore the therapeutic potential of dietary bioactive compounds as adjunctive treatments in post-stroke recovery and highlight the need for dose-response optimization, biomarker-guided precision nutrition approaches for patient stratification, and large-scale trials to validate long-term efficacy and safety in diverse stroke populations.