Xanthotoxol alleviates secondary brain injury after intracerebral hemorrhage by inhibiting microglia-mediated neuroinflammation and oxidative stress

Oxidative damage and inflammation are two critical mechanisms underlying secondary brain injury (SBI) following intracerebral hemorrhage (ICH). Xanthotoxol is reported to alleviate brain edema and inhibit inflammatory responses. Herein, we investigated the effects of xanthotoxol and its related mechanisms in SBI post-ICH. To explore the clinical effects of xanthotoxol an animal model of ICH was established. Neurological scores, survival rates and brain water content were measured. Inflammatory responses and oxidative damage in the peri-hemorrhagic areas were determined by measuring pro-inflammatory cytokines and oxidative related factors. The activation of the M1/M2 phenotype was detected by western blotting and immunofluorescence. Xanthotoxol improved the neurological functions and reduced cerebral edema in ICH mice. Additionally, xanthotoxol inhibited microglia activation and promotes microglial phagocytosis. Simultaneously, xanthotoxol promoted the transformation of BV2 cells from M1 phenotype to M2 phenotype, and protected BV2 cells against hemin-induced inflammation and oxidative stress. Mechanistically, xanthotoxol inactivated the NF-κB p65 signaling pathway in the hemin-challenged BV2 cells. Xanthotoxol ameliorates SBI post-ICH by suppressing microglia-mediated neuroinflammation and oxidative stress and enhancing microglial phagocytosis through inhibition of NF-κB signaling.