Poliumoside Exhibits Neuroprotective Effects against Cerebral Ischemia-Reperfusion Injury by Relieving Microglia-Mediated Neuronal Damage and Astrocytic Activation

Excessive activation of microglia contributes to neuronal damage and astrocytic activation during cerebral ischemia and hypoxia. Poliumoside (Pol) is a caffeoylated phenylpropanoid glycoside with significant anti-inflammatory and antioxidant functions. However, whether Pol can mediate microglia-mediated neurotoxicity in the ischemic brain remains nebulous. Here, a cerebral ischemia-reperfusion injury (CI/RI) mouse model was conducted to investigate Pol's role in microglial activation and neurotoxicity. We found that Pol significantly reduced neurological deficits, cerebral infarction volume, and neuronal damage in the CI/RI mouse model. Pol inhibited proinflammatory cytokines and microglial and astrocytic activation, while enhancing anti-inflammatory cytokines. Mechanistically, Pol markedly suppressed Fstl1, NF-κB phosphorylation, and the Nlrp3-Asc-Caspase1 inflammasome. In the oxygen-glucose-deprivation (OGD)-mediated BV2 microglia, Fstl1 overexpression significantly enhanced microglial activation. The conditioned medium of Fstl1-overexpressed microglia promoted astrocytic activation and neuronal injuries. However, Pol treatment or NF-κB pathway inhibition reversed Fstl1-mediated effects. In conclusion, Pol restrained microglia-modulated neuroinflammation and neurotoxicity in the cerebral hypoxic-ischemic model by restraining the Fstl1-NF-κB pathway.

Fstl1; cerebral hypoxic-ischemic; microglia; neurotoxicity; poliumoside.