Zeaxanthin exerts anti-inflammatory effects in vitro and provides significant neuroprotection in mice subjected to transient middle cerebral artery occlusion

Background and aims

Preclinical and clinical evidence supports the value of nutraceuticals as prophylactic or adjuvant therapeutics to reduce stroke risk or to improve post-stroke recovery. Given the beneficial properties of xantophyll carotenoids, we aimed at assessing the putative neuroprotective effects of zeaxanthin, evaluating its anti-inflammatory and anti-oxidant properties in vitro and in vivo.

Methods and results

Exposure to zeaxanthin (25 μM for 24 h) reverted the elevation of inducible nitric oxide synthase (iNOS) expression prompted by tumor necrosis factor (TNF)-α in macrophages from mouse bone marrow. In mice subjected to transient (30-min) middle cerebral artery occlusion (MCAo), oral pre-treatment with zeaxanthin (2 mg/kg, 48 h, 24 h and 1 h before MCAo) prevented the elevation of serum levels of reactive oxygen species induced by the ischemic insult, while it did not affect the reduction of antioxidant barrier efficiency. Analysis of lipid peroxidation showed a significant increase in hydroperoxide level in the brain of mice subjected to MCAo, and the latter effect was inhibited by pretreatment with zeaxanthin. Finally, we originally demonstrated that oral administration of zeaxanthin significantly reduced neurological deficits and brain damage caused by transient MCAo in mice.

Conclusions

Our data, in combination with the evidence that zeaxanthin is a well-tolerated carotenoid, strengthen the nutritional value of this xanthophyll in the prevention of ischemic stroke injury.