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

doi:10.1016/j.neuropharm.2004.12.013

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

Department of Molecular Medicine

Research output: Contribution to journal › Article › peer-review

68 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 language	English
Pages (from-to)	743-756
Number of pages	14
Journal	Neuropharmacology
Volume	48
Issue number	5
DOIs	https://doi.org/10.1016/j.neuropharm.2004.12.013
State	Published - 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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10.1016/j.neuropharm.2004.12.013

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title = "Protective effects of ginseng saponins on 3-nitropropionic acid-induced striatal degeneration in rats",

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.",

keywords = "3-Nitropropionic acid, Ginseng saponins, Neuroprotection, Striatum toxicity",

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

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.",

year = "2005",

month = apr,

doi = "10.1016/j.neuropharm.2004.12.013",

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AU - Kim, Jong Hoon

AU - Kim, Sunoh

AU - Yoon, In Soo

AU - Lee, Jong Hwan

AU - Jang, Byung Jun

AU - Jeong, Sang Min

AU - Lee, Jun Ho

AU - Lee, Byung Hwan

AU - Han, Jin Soo

AU - Oh, Sekwan

AU - Kim, Hyung Chun

AU - Park, Tae Kyu

AU - Rhim, Hyewhon

AU - Nah, Seung Yeol

N1 - 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.

PY - 2005/4

Y1 - 2005/4

N2 - 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.

AB - 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.

KW - 3-Nitropropionic acid

KW - Ginseng saponins

KW - Neuroprotection

KW - Striatum toxicity

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SN - 0028-3908

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IS - 5

ER -

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

Abstract

Bibliographical note

Keywords

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