Picroside II Exerts a Neuroprotective Effect by Inhibiting the Mitochondria Cytochrome C Signal Pathway Following Ischemia Reperfusion Injury in Rats.

Abstract

Stroke is a common neurodegenerative disease in the wide world, and mitochondrial defects underlie the pathogenesis of ischemia, especially during reperfusion. Picroside II, the principal active component of Picrorhiza, is a traditional Chinese medicine. Our previous study demonstrated that the best therapeutic dose and time window were injection of picroside II at a dose of 10-20mg/kg body weight following cerebral ischemia by 1.5-2.0h. In this paper, the neuroprotective effect and the mechanism of picroside II were investigated, as well as its involvement in antioxidant and mitochondria cytochrome C (CytC) signal pathway following ischemia reperfusion (I/R) injury in rats. After 24h of cerebral I/R, the neurobehavioral function was measured by modified neurological severity score test; the content of reactive oxygen species in brain tissue was measured by enzyme-linked immunosorbent assay; the cerebral infarction volume was detected by TTC staining; the morphology of brain tissue was observed by hematoxylin-eosin; the apoptotic cells were counted by terminal deoxynucleotidyl transferase dUTP nick end labeling assay; the ultrastructure of the cortical brain tissues was observation by transmission electron microscopy; the expressions of CytC and Caspase-3 were determined by immunohistochemical assay and Western blot. The results indicated that picroside II could scavenge ROS contents, decrease the cerebral infarction volume and apoptotic cells, protect the structure of mitochondria, down-regulate the expression of CytC and Caspase-3 in cerebral I/R rats. It can be concluded that picroside II exerts a neuroprotective effect by inhibiting the mitochondria CytC signal pathway following ischemia reperfusion injury in rats.