Astaxanthin in cerebrovascular diseases: Pharmacokinetics, delivery systems, dietary safety, and multitarget mechanisms of action.

Cerebrovascular diseases are characterized by high incidence and prevalence, substantial disability, and complex pathological mechanisms. Current therapeutic interventions have limited efficacy, highlighting the need to develop novel multitarget strategies. Astaxanthin, a natural lipid-soluble keto-carotenoid, possesses a unique molecular structure that facilitates its penetration of the blood-brain barrier. It also exerts potent antioxidant effects by scavenging free radicals and inhibiting lipid peroxidation. This review comprehensively summarizes advances in the pharmacokinetics, dietary safety profile, delivery systems, and mechanisms of action of astaxanthin in cerebrovascular diseases. Preclinical evidence indicates that astaxanthin modulates signaling pathways, including nuclear factor erythroid 2-related factor 2/heme oxygenase-1 and phosphoinositide 3-kinase/protein kinase B/ mechanistic target of rapamycin signaling, while attenuating neuroinflammation by reducing interleukin-1 beta, tumor necrosis factor alpha, and nuclear factor kappa B signaling; alleviating oxidative stress by enhancing superoxide dismutase activity and glutathione levels and reducing malondialdehyde accumulation; exerting anti-apoptotic effects through the modulation of B-cell lymphoma 2-associated X protein, B-cell lymphoma 2, and cysteine-aspartic protease 3; and inhibiting ferroptosis by regulating glutathione peroxidase 4 and solute carrier family 7 member 11. In animal models of ischemic stroke, hemorrhagic stroke, vascular dementia, and atherosclerosis, astaxanthin has been shown to reduce infarct volume, alleviate cerebral edema, reduce cognitive deficits, and stabilize atherosclerotic plaques. Various lipid-based, polymer-based, and biomimetic delivery systems have been developed to enhance its bioavailability. However, current research faces critical challenges, including substantial model heterogeneity, insufficient mechanistic depth, and the complete absence of randomized controlled trials in patients with cerebrovascular diseases. This review consolidates the preclinical evidence supporting the multitarget effects of astaxanthin, clarifies its potential as a candidate compound for further investigation, and addresses the associated translational challenges. Furthermore, it provides a theoretical basis for future standardized preclinical evaluations and the design of randomized controlled trials.