Abstract
Betulinic acid (BA) is a natural pentacyclic triterpenoid compound, which has been known for its anti-inflammatory and anti-apoptosis activities.However, the effects of BA on cerebral ischemia/reperfusion (I/R) injury of rats remain unclear. In the study, rats were randomly divided into sham group, I/R group, I/R+BA 20mg/kg group, I/R+BA 40 mg/kg group, I/R+BA 80 mg/kg group and I/R+edaravone group. Neurofunction deficit was evaluvated by Longa score. The cerebral infarct volume was detected by TTC staining. The apoptosis in neuronal cells were detected by terminal deoxynucleoitidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and the expression of ERK, p-ERK, cleaved caspase-3, Bax and Bcl-2 were detected by western blot. The neurobehavioral score of rats in I/R group increased remarkably compared with sham group and neurobehavioral score was significantly decreased by pretreating with BA. Cerebral infarct volume was reduced after pretreatment with BA. The result of TUNEL assay showed the rats pretreated with 20, 40 and 80mg/kg BA has lower neuronal cell apoptosis rate than the one of rats in I/R group. The expression of p-ERK, cleaved caspase-3 and the ratio of Bax/Bcl-2 were increased in rats suffered from I/R injury, BA pretreatment significantly reduced the expression of p-ERK, cleaved caspase-3 and the ratio of Bax/Bcl-2. These results suggested that the neuroprotection of BA against cerebral I/R injury may relate to its anti-apoptosis effect, which may relate to the inhibition of ERK kinase and reduction of Cleaved caspase-3 and the ratio of Bax/Bcl-2 (fig as below)
