Chitosan-based polymeric nanocarrier has been utilized as a novel drug delivery device in recent years due to its prominent role in the treatment of central nervous system disorders. The aim of this study was to investigate the anti-oxidative and anti-inflammatory effects of silymarin-loaded chitosan nanoparticles (SM–CS–NPs) on rat model of global cerebral ischemia/reperfusion (I/R). All rats were randomly distributed into four groups: Control, I/R, SM and SM–CS–NPs. Oral administration of SM and SM–CS–NPs was started 14 days prior to bilateral common carotid artery occlusion (BCCAO). Depressive-like behaviors, infarct volume, some oxidative stress markers and inflammatory factors were assessed after induction of I/R. SM–CS–NPs pretreatment significantly ameliorated depressive-like behaviors and infarct volume after I/R. SM–CS–NPs also significantly decreased the levels of malondialdehyde (MDA), and expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and significantly increased the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GRx), and glutathione (GSH) levels in I/R brain. The current study demonstrated that SM–CS–NPs pretreatment effectively prevents oxidative and inflammatory damage in the brain caused by I/R, and it can be considered as a useful pretreatment to attenuate the negative effects of I/R.
