Protective effect of fangchinoline on cyanide-induced neurotoxicity in cultured rat cerebellar granule cells

The present study was performed to examine the effect of fangchinoline, a bis-benzylisoquinoline alkaloid, which exhibits the characteristics of a Ca2+ channel blocker, on cyanide-induced neurotoxicity using cultured rat cerebellar granule neurons. NaCN produced a concentration-dependent reduction of cell viability, which was blocked by MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, verapamil, L-type Ca2+ channel blocker, and L-NAME, a nitric oxide synthase inhibitor. Pretreatment with fangchinoline over a concentration range of 0.1 to 10 muM significantly decreased the NaCN-induced neuronal cell death, glutamate release into medium, and elevation of [Ca2+](i) and oxidants generation. These results suggest that fangchinoline may mitigate the harmful effects of cyanide-induced neuronal cell death by interfering with [Ca2+](i) influx, due to its function as a Ca2+ channel blocker, and then by inhibiting glutamate release and oxidants generation.