[Aim] Extracellular zinc enhances pro-inflammatory cytokines secretion from M1 microglia via reactive oxygen species (ROS) generation. Here, we examined the effect of peridinin, a carotenoid in dinoflagellates, on the zinc-enhanced inflammatory M1 phenotype.

[Methods] M1 polarization of mouse microglia prepared was induced by lipopolysaccharide after ZnCl₂ treatment in the presence of peridinin, and cytokines secretion were assessed by ELISA. In addition, ROS detection assay and HPLC analysis were performed. Transient ischemia in mice was induced 5 min after peridinin injection. The levels of cytokines and M1 marker were examined by qPCR and immunostaining, respectively. Spatial memory was assessed by Y-maze test.

[Results] Peridinin prevented the zinc-induced aggravation of cytokines secretion from M1 microglia and increase in the microglial ROS levels. No shift in the absorption maximum of peridinin reacted with zinc was observed. Injection of peridinin suppressed ischemia-induced expression of cytokines and M1 marker, and memory impairment.

[Conclusion] These results suggest that peridinin exerts neuroprotective effects against the drastic post-ischemic inflammation by inhibiting the zinc-induced increase in the microglial ROS levels.