Dammarane derivatives protect cultured rat cortical cells from glutamate-induced neurotoxicity

We previously reported that ginsenosides Rb-1 and Rg(3), dammarane glycosides, of Panax ginseng C. A. Meyer (Araliaceae), significantly attenuated glutamate-induced neurotoxicity in primary cultures of rat cortical cells. To seek more potent neuroprotective compounds, we attempted to modify the chemical structure of dammarane glycosides and obtained six derivatives, MA-11, PT-11, PT-111, POA-101, POA-111 and N-001. The neuroprotective activity of these dammarane derivatives were evaluated employing primary cultures of rat corticoid cells. The glutamate-induced neuronal cell damage was significantly reduced by a pre-treatment with protopanaxadiol, MA-11 or PT-11 at concentrations ranging from 100 nM to 10 muM. Both MA-11 and PT-11, preserved the levels of catalase and inhibited decreases in glutathione reductase in glutamate-injured cells. Furthermore, the dammarane derivatives reduced the content of intracellular peroxide in glutamate-intoxicated cells. Finally, they inhibited the formation of malondialdehyde, a compound produced during lipid peroxidation, in glutamate-insulted cells. These results show that the dammarane derivatives, MA-11 and PT-11. exert significant neuroprotective effects on cultured cortical cells by a mechanism seemingly distinct from that afforded by ginsenosides Rb-1 and Rg(3). As such, the dammarane derivatives may be efficacious in protecting neurons from oxidative damage caused by exposure to excess glutamate.