Protective effects of the astaxanthin derivative, adonixanthin, on brain hemorrhagic injury

•Carotenoids are effective against hemorrhagic brain injury.•Adonixanthin exerted protective effects against oxidative stress.•Adonixanthin improved BBB permeability in an autologous blood injection model. Astaxanthin is beneficial for human health and is used as a dietary supplement. The present study was performed in order to examine the protective effects of the astaxanthin derivative, adonixanthin, against cell death caused by hemoglobin, collagenase, lipopolysaccharide, and hydrogen peroxide, which are associated with hemorrhagic brain injury. In an in vitro study, adonixanthin exerted cytoprotective effects against each type of damage, and its effects were stronger than those of astaxanthin. The increased production of reactive oxygen species in human brain endothelial cells in the hemoglobin treatment group was inhibited by adonixanthin. Moreover, adonixanthin suppressed cell death in SH-SY5Y cells. In an in vivo study, the oral administration of adonixanthin improved blood-brain barrier hyper-permeability in an autologous blood ICH model. We herein demonstrated for the first time that adonixanthin exerted protective effects against hemorrhagic brain damage by activating antioxidant defenses, and has potential as a protectant against intracerebral hemorrhage.