Asiatic acid exerts neuroprotective effect against hypoxicischemic brain injury in neonatal rats via inhibition of oxidative damage

Abstract

Purpose: To investigate the effect of asiatic acid on hypoxic ischemia-induced injury in neonatal rats, and the underlying mechanism of action.Methods: Hypoxic-ischemia (HI) neonatal rat model was established via permanent ligation of the carotid artery, followed by hypoxia (exposure to 8 % oxygen and 92 % nitrogen) for 24 h. Immunofluorescence, using fluorescence microscope, was used for the determination of expressions of p-TAK1, NeuN and GFAP. Western blotting was used for assaying protein expression levels, while TUNEL assay was employed for the measurement of apoptosis.Results: Treatment of rats with asiatic acid prior to HI effectively prevented up-regulation of pTAK1 and decreased the count of p-TAK1-containing astrocytes. The proportion of NeuN containing p-TAK1 in HI rat brain cortex was significantly reduced by asiatic acid (p < 0.05). Treatment of rats with asiatic acid suppressed HI- induced up-regulation of pJNK expression. The HI-induced increase in the expression levels of caspase-3, p53 and p-c-Jun in rat brain cortex were reversed by asiatic acid (p < 0.05). The HImediated up-regulation of expressions of p- JNK, caspase-3, p53 and p-c-Jun in rat brain cortex were inhibited significantly by NG25. Asiatic acid treatment also significantly alleviated HI-mediated increase in apoptosis of neurons in rat brain cortex, when compared to model group (p < 0.05).Conclusion: These findings suggest that asiatic acid prevents HI-induced brain injury in neonatal rats via inhibition of neuronal apoptosis. Moreover, it inhibits TAK1 activation, suppresses p-JNK expression and targets pro-apoptotic factors in brain cortex. Therefore, asiatic acid may be a therapeutic agent for the management of HI-induced brain injury.