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

We previously reported that ginsenosides Rb-1 and Rg(3), dammarane glycosid es, of Panax ginseng C. A. Meyer (Araliaceae), significantly attenuated glu tamate-induced neurotoxicity in primary cultures of rat cortical cells. To seek more potent neuroprotective compounds, we attempted to modify the chem ical 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 r at corticoid cells. The glutamate-induced neuronal cell damage was significantly reduced by a p re-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 catal ase and inhibited decreases in glutathione reductase in glutamate-injured c ells. Furthermore, the dammarane derivatives reduced the content of intrace llular peroxide in glutamate-intoxicated cells. Finally, they inhibited the formation of malondialdehyde, a compound produced during lipid peroxidatio n, in glutamate-insulted cells. These results show that the dammarane derivatives, MA-11 and PT-11. exert s ignificant neuroprotective effects on cultured cortical cells by a mechanis m seemingly distinct from that afforded by ginsenosides Rb-1 and Rg(3). As such, the dammarane derivatives may be efficacious in protecting neurons fr om oxidative damage caused by exposure to excess glutamate.