Muscone Exerts Neuroprotection in an Experimental Model of Stroke via Inhibition of the Fas Pathway

作者：Wei, Gang; Chen, Dong Feng^*; Lai, Xiao Ping; Liu, Dong Hui; Deng, Ru Dong; Zhou, Jian Hong; Zhang, Sai Xia; Li, Yi Wei; Li, Hui; Zhang, Qiong Dan

来源：Natural Product Communications, 2012, 7(8): 1069-1074.

• Muscone
• Small molecules
• Neuronal apoptosis
• Fas death pathway
• Cerebral ischemia

Identifying small molecules that are neuroprotective against stroke injury will be highly beneficial for treatment therapies. A cell viability assay and gas chromatography-mass spectrometry were used to identify active small molecules in XingNaoJing, which is a well known Chinese Medicine prescribed for the effective treatment of stroke. Studies have found that muscone is the active compound that prevents PC12 cell and cortical neuron damage following various injuries. Analysis of apoptosis indicated that muscone inhibited glutamate-induced apoptotic cell death of PC12 cells and cortical neurons. Fas and caspase-8 expression were upregulated following glutamate treatment in cortical neurons, and was markedly attenuated in the presence of muscone. Furthermore, muscone significantly reduced cerebral infarct volume, neurological dysfunction and inhibited cortical neuron apoptosis in middle cerebral artery occluded (MCAO) rats in a dose-dependent manner. Moreover, a significant decrease in Fas and caspase-8 expression in the rat cortex was observed in MCAO rats treated with muscone. Our results demonstrate that muscone may be a small active molecule with neuroprotective properties, and that inhibition of apoptosis and Firs is an important mechanism of neuroprotection by muscone. These findings suggest a potential therapeutic role for muscone in the treatment of stroke.

• 出版日期2012-8
• 单位广州中医药大学