Citrus Flavanones as Neuroprotective Agents: Mechanisms and Dietary Relevance in Ischemic Stroke

Neuroprotection is pivotal in ischemic stroke management. Citrus flavanones, abundant in citrus fruits and their derived products, demonstrate significant neuroprotective potential, yet a comprehensive review of their roles in ischemic stroke is lacking. This review clarifies their mechanisms and applications for ischemic stroke prevention/treatment. Profiles of citrus flavanones in different dietary sources are summarized, and the dietary relevance of the concentrations used in preclinical studies is critically discussed. Citrus flavanones exert protection through diverse mechanisms, including antioxidation, anti-inflammation, mitochondrial protection, autophagy modulation, apoptosis inhibition, endoplasmic reticulum stress suppression, and blood–brain barrier (BBB) preservation, with angiogenesis promotion also suggested. They interact with the central nervous system either directly by crossing the BBB or indirectly via the microbiome–gut–brain axis. This review offers valuable insights to guide future research and the development of citrus-flavanone-based functional foods or therapeutics for ischemic stroke.