AIMTo study the effects of ginkgolides (Gin) on the expression of hypoxia-inducible factor-1alpha (H1F-1alpha) in primary cultured cortical neurons treated with CoCl2 and the relationship with ERK signal pathway.

METHODSWe observed the effects of Gin (37.5 mg/L) on morphology and viability on primary cultured cortical neurons with treatment of CoCl2 (125 micromol/L). The expression of HIF-1alpha and p-ERK of neurons induced by CoCl2 pretreated with Gin were assessed by Western-blot. We analyzed the relationship between HIF-1alpha expression activated by Gin and ERK signal pathway with treatment of PD98059 (100 micromol/L), a selective inhibitor of ERK.

RESULTSIt was shown that Gin had protective effects on CoCl2 damaged neurons by raising the neuronal viability. Some basic expression of HIF-1alpha and p-ERK were observed in normal cultured cortical neurons. The expression of HIF-1alpha and p-ERK increased strikingly when treated with CoCl2 for 4 h. The levels of HIF-1alpha and p-ERK increased even more in the neurons pretreated with Gin for 24 h before CoCl2. The levels of HIF-1alpha and p-ERK were notably inhibited with pretreatment of PD98059, while Gin could prevent this inhibition.

CONCLUSIONGin has protective effects on neurons damaged by CoCl2 which might be related to the increase of the level of HIF-1alpha and the activation of ERK signal pathway.