5,7-Dimethoxycoumarin inhibits neuronal apoptosis by targeting caspase-3 expression in rats with acute cerebral infarction
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
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