title: Muscone exerts neuroprotection in an experimental model of stroke via inhibition of the fas pathway.
abstract: 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 Fas is an important mechanism of neuroprotection by muscone. These findings suggest a potential therapeutic role for muscone in the treatment of stroke.
authors.affiliation: Research & Development of New Drugs, Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wei
authors.forename: Dong-Feng
authors.initials: DF
authors.lastname: Chen
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Lai
authors.forename: Dong-Hui
authors.initials: DH
authors.lastname: Liu
authors.forename: Ru-Dong
authors.initials: RD
authors.lastname: Deng
authors.forename: Jian-Hong
authors.initials: JH
authors.lastname: Zhou
authors.forename: Sai-Xia
authors.initials: SX
authors.lastname: Zhang
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Qiong-Dan
authors.initials: QD
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy; D003516:Cycloparaffins / Q000494:pharmacology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology; D019014:fas Receptor / Q000037:antagonists & inhibitors*
chemical_list: D003516:Cycloparaffins; C491898:Fas protein, rat; D018696:Neuroprotective Agents; D019014:fas Receptor; C031021:muscone