Protective effects of ginseng saponins on 3-nitropropionic acid-induced striatal degeneration in rats

Jong Hoon Kim, Sunoh Kim, In Soo Yoon, Jong Hwan Lee, Byung Jun Jang, Sang Min Jeong, Jun Ho Lee, Byung Hwan Lee, Jin Soo Han, Sekwan Oh, Hyung Chun Kim, Tae Kyu Park, Hyewhon Rhim, Seung Yeol Nah

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67 Scopus citations

Abstract

The precise cause of neuronal cell death in Huntington's disease (HD) is not known. Systemic administration of 3-nitropropionic acid (3-NP), an irreversible succinate dehydrogenase inhibitor, not only induces a cellular ATP depletions but also causes a selective striatal degeneration similar to that seen in HD. Recent accumulating reports have shown that ginseng saponins (GTS), the major active ingredients of Panax ginseng, have protective effects against neurotoxin insults. In the present study, we examined in vitro and in vivo effects of GTS on striatal neurotoxicity induced by repeated treatment of 3-NP in rats. Here, we report that systemic administration of GTS produced significant protections against systemic 3-NP- and intrastriatal malonate-induced lesions in rat striatum with dose-dependent manner. GTS also improved significantly 3-NP-caused behavioral impairment and extended survival. However, GTS itself had no effect on 3-NP-induced inhibition of succinate dehydrogenase activity. To explain the mechanisms underlying in vivo protective effects of GTS against 3-NP-induced striatal degeneration, we examined in vitro effect of GTS against 3-NP-caused cytotoxicity using cultured rat striatal neurons. We found that GTS inhibited 3-NP-induced intracellular Ca2+ elevations. GTS restored 3-NP-caused mitochondrial transmembrane potential reduction in cultured rat striatal neurons. GTS also prevented 3-NP-induced striatal neuronal cell deaths with dose-dependent manner. The EC50 was 12.6 ± 0.7 μg/ml. These results suggest that in vivo protective effects of GTS against 3-NP-induced rat striatal degeneration might be achieved via in vitro inhibition of 3-NP-induced intracellular Ca2+ elevations and cytotoxicity of striatal neurons.

Original languageEnglish
Pages (from-to)743-756
Number of pages14
JournalNeuropharmacology
Volume48
Issue number5
DOIs
StatePublished - Apr 2005

Bibliographical note

Funding Information:
This work was supported by the Ministry of Science and Technology through the Bio-Food and Drug Research Center at Konkuk University, Chungju, Korea.

Keywords

  • 3-Nitropropionic acid
  • Ginseng saponins
  • Neuroprotection
  • Striatum toxicity

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