Fucoxanthin alleviates secondary brain injury in mice following intracerebral hemorrhage via PI3K-mediated inhibition of NF-κB signaling pathway

Background: ICH is an acute clinical cerebrovascular disease without effective treatments. This study was designed to investigate the therapeutic value of fucoxanthin in ICH treatment. Methods: Animal ICH models were established by collagenase IV injection. ICH mice were given intraperitoneal injection of fucoxanthin (100 mg/kg). Neurological deficits, brain edema, blood-brain barrier (BBB) integrity, and histological impairment were assessed. Nissl staining and TUNEL staining were performed to detect neuronal cell loss and apoptosis. The levels of tight junction proteins, apoptosis-related proteins, Iba-1, and pathwayrelated proteins were measured by immunofluorescence staining, western blotting, and ELISA. Results: Fucoxanthin administration attenuated neurological deficits and brain injuries following ICH. Additionally, fucoxanthin alleviated neuronal apoptosis caused by ICH. Moreover, fucoxanthin inhibited microgliamediated inflammation and M1 polarization in ICH models. Mechanistically, fucoxanthin inactivated the NF kappa B pathway and triggered the activation of PI3K/Akt signaling after ICH, and LY294002 (a PI3K inhibitor) compromised the protective effect of fucoxanthin. Conclusion: Fucoxanthin alleviates ICH-induced neurological deficits and brain injuries by suppressing the PI3K/ Akt-mediated NF-kappa B pathway to inhibit M1 polarization and attenuate neuroinflammation, neuronal apoptosis, BBB dysfunction, and brain edema.