Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

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

Ying Wang¹, Huiping Wang², Pu Zhao³, Jiwen Cheng¹, Wei Gong¹, Juan Zhang⁴

¹Department of Pediatric Surgery; ²Department of Neonatology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004; ³Department of Neonatology, Shaanxi Provincial People's Hospital, Xi'an 710068; ⁴Department of Neonatology, Northwest Women and Children's Hospital, Xi'an 710061, Shaanxi, China.

For correspondence:- Juan Zhang Email: dy3893@126.com Tel:+8613435678226

Accepted: 11 August 2021 Published: 30 September 2021

Citation: Wang Y, Wang H, Zhao P, Cheng J, Gong W, Zhang J. Asiatic acid exerts neuroprotective effect against hypoxic-ischemic brain injury in neonatal rats via inhibition of oxidative damage. Trop J Pharm Res 2021; 20(9):1903-1908 doi: 10.4314/tjpr.v20i9.17

© 2021 The authors.
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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 HI-mediated 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.

Keywords: Hypoxic-ischemic, Neuroprotection, Epilepsy, Therapeutic, Apoptosis