Picroside II has a neuroprotective effect by inhibiting ERK 1/2 activation after cerebral ischemic injury in rats

Summary In the study, the neuroprotective effect and underlying mechanism of picroside II were explored, and its involvement in the ERK 1/2 signal pathway after cerebral ischemia injury in rats. A monofilament thread was inserted to generate middle cerebral artery occlusion ( MCAO ) in 100 Wistar rats that were administered an intraperitoneal injection of picroside II (20 mg/kg). The neurobehavioural function of rats was evaluated using a modified neurological severity score ( mNSS ) test. The cerebral infarct volume ( CIV ) was measured using tetrazolium chloride ( TTC ) staining. The morphology and ultra‐structure of the nerve cells in the cortex were observed using hematoxylin and eosin ( HE ) staining and transmission electron microscopy ( TEM ), respectively. The apoptotic cells were counted using the terminal deoxynucleotidyl transferase dUTP nick end labeling ( TUNEL ) assay. The expression of extracellular signal‐regulated kinase 1/2 ( pERK 1/2) in the cortex was determined using immunohistochemistry and Western blot analysis. Neurological dysfunction was observed in all rats with MCAO . In both the model and lipopolysaccharide ( LPS ) groups, the CIV increased, the neuronal damage in the cortex was more severe, and the number of apoptotic cells and the pERK 1/2 expression significantly increased compared with the control group ( P  < 0.05). In treatment and U0126 groups, the neurological function was improved, the CIV decreased, the neuronal damage in the cortex was attenuated, and the number of apoptotic cells and the pERK 1/2 expression significantly decreased compared with the model group ( P  < 0.05). No significant differences in these indices were observed between model and LPS groups or treatment and U0126 groups ( P  > 0.05). The results suggest that activation of ERK 1/2 in cerebral ischaemia induces neuronal apoptosis and picroside II may reduce neuronal apoptosis to confer protection against cerebral ischemic injury by inhibiting ERK 1/2 activation.