Neuroinflammation mediated by microglia made a significant contribution in the pathophysiology of epilepsy. Icariin (ICA), a bioactive ingredient isolated from Epimedium, has been shown to present both antioxidant and anti-inflammatory properties. This study was to explore the potential therapeutic effects of icariin on mouse pilocarpine model of epilepsy and its underlying mechanisms in vivo and in vitro. To this end, we firstly measured the serum concentrations of the proinflammatory cytokines IL-1β and IL-6 from patients with temporal lobe epilepsy and found that patients with a higher seizure frequency showed correspondingly higher inflammatory reaction. Mouse pharmacokinetic study, transmembrane transportation assay, and cell viability assay collectively demonstrated that ICA was able to cross the blood-brain barrier and has good biocompatibility. The acute and chronic epilepsy models were next established in a pilocarpine mouse model of acquired epilepsy. Icariin has been identified that it could cross the blood-brain barrier and enter the hippocampus to exhibit therapeutic effects. ICA treatment dramatically promoted microglial polarization to the M2 phenotype in epilepsy mice both in the acute and chronic phases. Reduced release of M1-associated proinflammatory factors, such as IL-1β and IL-6, corroborates the altered glial cell polarization. Furthermore, ICA alleviated seizure intensity and mortality in acute phase epileptic mice. Models in the chronic group also showed improved general condition, cognition ability, and memory function after ICA treatment. Taken together, our research strongly suggested that icariin has the potential to treat epilepsy via inhibiting neuroinflammation by promoting microglial polarization to the M2 phenotype.
Keywords: Epilepsy; Icariin; Immunoregulation; Microglial polarization; Neuroinflammation.
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