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

S. R. Kim, S. H. Sung, S. W. Kwon, J. H. Park, H. Huh, Y. C. Kim

Research output: Contribution to journalArticle

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Abstract

We previously reported that ginsenosides Rb1 and Rg3, 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 μM. 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 Rb1 and Rg3. As such, the dammarane derivatives may be efficacious in protecting neurons from oxidative damage caused by exposure to excess glutamate.

Original languageEnglish (US)
Pages (from-to)1505-1511
Number of pages7
JournalJournal of Pharmacy and Pharmacology
Volume52
Issue number12
DOIs
StatePublished - 2000

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Glutamic Acid
Glycosides
Araliaceae
Panax
Glutathione Reductase
Peroxides
Neuroprotective Agents
Malondialdehyde
Catalase
Lipid Peroxidation
dammarane
Cultured Cells
Adrenal Cortex Hormones
Neurons
ginsenoside Rg3
ginsenoside Rb1

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Dammarane derivatives protect cultured rat cortical cells from glutamate-induced neurotoxicity. / Kim, S. R.; Sung, S. H.; Kwon, S. W.; Park, J. H.; Huh, H.; Kim, Y. C.

In: Journal of Pharmacy and Pharmacology, Vol. 52, No. 12, 2000, p. 1505-1511.

Research output: Contribution to journalArticle

Kim, S. R. ; Sung, S. H. ; Kwon, S. W. ; Park, J. H. ; Huh, H. ; Kim, Y. C. / Dammarane derivatives protect cultured rat cortical cells from glutamate-induced neurotoxicity. In: Journal of Pharmacy and Pharmacology. 2000 ; Vol. 52, No. 12. pp. 1505-1511.
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