The effects of huperzine A (HupA) on staurosporine-induced neuronal apoptosis and potential mechanisms were investigated in primary cultured rat cortical neurons. Pretreatment of the cells with HupA (0.1-100 microM) 2 h prior to 0.5 microM staurosporine exposure for 24 h, markedly elevated cell survival. Incubation with HupA at higher dose (1 microM) also reduced the DNA fragmentation caused by staurosporine. This dose of HupA also reduced the upregulation of the pro-apoptotic gene, bax, downregulation of the anti-apoptotic gene, bcl-2, and antagonized the decrease in immunoreactive caspase-3 proenzyme. These results demonstrated that HupA protect neurons against staurosporine-induced apoptosis via regulating the apoptotic related genes and caspase-3 proenzyme.
Copyright 2003 Elsevier Science Ireland Ltd.