Picroside II has a neuroprotective effect by inhibiting ERK1/2 activation after cerebral ischemic injury in rats.

In the study, the neuroprotective effect and underlying mechanism of picroside II were explored, and its involvement in the ERK1/2 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 (pERK1/2) 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 pERK1/2 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 pERK1/2 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 ERK1/2 in cerebral ischaemia induces neuronal apoptosis and picroside II may reduce neuronal apoptosis to confer protection against cerebral ischemic injury by inhibiting ERK1/2 activation.