Tao Ma1 ,
Chunxia Wang2
1Department of Neurology, Xintai Municipal People's Hospital, Xintai 271200;
2Taishan Sanatorium of Shandong Province, Taishan, Shandong 271000, China.
For correspondence:- Tao Ma
Email: taoma356@hotmail.com Tel:+8631186556820
Received: 22 November 2016
Accepted: 16 March 2017
Published: 30 April 2017
Citation:
Ma T, Wang C.
5,7-Dimethoxycoumarin inhibits neuronal apoptosis by targeting caspase-3 expression in rats with acute cerebral infarction. Trop J Pharm Res 2017; 16(4):877-883
doi:
10.4314/tjpr.v16i4.19
© 2017 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..
Abstract
Purpose: To investigate the effect of 5,7-dimethoxycoumarin on inhibition of neuronal apoptosis in a rat model of acute cerebral infarction.
Methods: Occlusion of middle cerebral artery was used for the preparation of a rat model of cerebral infarction. The rats in the treatment group were given 15 mg/kg dose of 5,7-dimethoxycoumarin daily for 30 days intraperitoneally. However, those in the normal control and model groups received the same volume of normal saline. The rats were sacrificed after anaesthetization to extract brain samples.
Results: Quantitative polymerase chain reaction (PCR) analysis showed a significant (p < 0.02) decrease in the level of caspase-3 mRNA by 5,7-dimethoxycoumarin compared to the model group. Western blot assay data revealed significant decrease in caspase-3 protein expression by 5,7-dimethoxycoumarin. The higher activity of caspase-3 in acute cerebral infarction rats was reduced significantly (p < 0.005) following treatment with 15 mg/kg dose of 5,7-dimethoxycoumarin for 30 days. Treatment of the acute cerebral infarction rats with 15 mg/kg dose of 5,7-dimethoxycoumarin daily for 30 days led to a greater decrease in apoptotic index than those of rats with model group (p < 0.005). 5,7-Dimethoxycoumarin treatment daily for 30 days at a dose of 15 mg/kg also caused a significant (p < 0.005) decrease in neurological impairment score compared to the model animal group.
Conclusion: 5,7-Dimethoxycoumarin successfully inhibits neuronal apoptosis via inhibition of the expression of caspase-3 in brain tissues and thus may be useful for cerebral infarction therapy
Keywords: Cerebral infarction, 5,7-Dimethoxycoumarin, Neurological impairment, Apoptosis, Caspase-3