Dammarane-Type Saponins from Gynostemma pentaphyllum prevent hypoxia-induced neural injury through activation of ERK, Akt and CREB pathways.

Gynostemma pentaphyllum possesses the neuroprotective bioactivity. However, the effect of gypenosides on the hypoxia-induced neural damage remains obscure. In this study, Gyp, the active fraction extracted from G. pentaphyllum, and its bioactive compounds as well as the underlying molecular mechanisms were investigated. Eighteen dammarane-type saponins were isolated from Gyp. The absolute configurations of six unreported compounds (13-18) were assessed via ECD analyses. The results of cell viability assay showed that Gyp and its bioactive compounds (13-16 and 18) effectively protected PC12 cells from hypoxia injury. Gyp pre-treatment also improved mice spatial memory impairment caused by hypoxia exposure. At the molecular level, Gyp and its bioactive compounds could activate the signaling pathways of ERK, Akt, and CREB in vitro and in vivo. In summary, Gyp and its bioactive compounds could prevent hypoxia-induced injury via ERK, Akt and CREB signaling pathways.