Icaritin promotes brain functional rehabilitation in ischemic stroke rats by regulating astrocyte activation and polarization via GPER.

Background: Cerebral ischemic injury induces the polarization of astrocytes toward two different phenotypes, i.e., the proinflammatory A1 phenotype and the protective, anti-inflammatory A2 phenotype, affects the prognosis of cerebral ischemia.

AD16 attenuates neuroinflammation induced by cerebral ischemia through down-regulating astrocytes A1 polarization.

A1 polarization of astrocytes mediated prolonged inflammation contributing to brain injury in ischemic stroke. We have previously shown that AD16 protects against neonatal hypoxic-ischemic brain damage in vivo and oxygen-glucose deprivation in vitro. More recently, AD16 has demonstrated safety, tolerability, and favorable pharmacokinetics in a randomized controlled phase I trial.

Icaritin alleviates cerebral ischemia‒reperfusion injury by regulating NMDA receptors through ERK signaling.

N-methyl-D-aspartate (NMDA) receptors are key signaling molecules that mediate excitotoxicity during cerebral ischemia. GluN2A-containing NMDA receptors, which are mostly located in the intrasynaptic region, mediate normal physiological processes and promote neuronal survival. GluN2B-containing NMDA receptors, which are mostly located in the extrasynaptic region, mediate excitotoxicity injury and promote neuronal death during ischemia.

Icaritin inhibits neuroinflammation in a rat cerebral ischemia model by regulating microglial polarization through the GPER-ERK-NF-κB signaling pathway.

Background: Activated microglia play a key role in initiating the inflammatory cascade following ischemic stroke and exert proinflammatory or anti-inflammatory effects, depending on whether they are polarized toward the M1 or M2 phenotype. The present study investigated the regulatory effect of icaritin (ICT) on microglial polarization in rats after cerebral ischemia/reperfusion injury (CI/RI) and explored the possible anti-inflammatory mechanisms of ICT.

Methods: A rat model of transient middle cerebral artery occlusion (tMCAO) was established.