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 Ca(2+) 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 EC(50) was 12.6 +/- 0. 7microg/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 Ca(2+) elevations and cytotoxicity of striatal neurons.
authors.affiliation: Research Laboratory for the Study of Ginseng Signal Transduction and Department of Physiology and Anatomy, College of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea.
authors.forename: Jong-Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Sunoh
authors.initials: S
authors.lastname: Kim
authors.forename: In-Soo
authors.initials: IS
authors.lastname: Yoon
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Lee
authors.forename: Byung-Jun
authors.initials: BJ
authors.lastname: Jang
authors.forename: Sang Min
authors.initials: SM
authors.lastname: Jeong
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Byung-Hwan
authors.initials: BH
authors.lastname: Lee
authors.forename: Jin-Soo
authors.initials: JS
authors.lastname: Han
authors.forename: Sekwan
authors.initials: S
authors.lastname: Oh
authors.forename: Hyung-Chun
authors.initials: HC
authors.lastname: Kim
authors.forename: Tae Kyu
authors.initials: TK
authors.lastname: Park
authors.forename: Hyewhon
authors.initials: H
authors.lastname: Rhim
authors.forename: Seung-Yeol
authors.initials: SY
authors.lastname: Nah
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D008297:Male; D009249:NADP; D005894:Panax / Q000737:chemistry*; D010421:Pentanoic Acids; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000737:chemistry / Q000627:therapeutic use*; D020955:Striatonigral Degeneration / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013778:Tetrazolium Salts; D013997:Time Factors
chemical_list: C089284:3-nitropivalic acid; D005904:Glial Fibrillary Acidic Protein; D010421:Pentanoic Acids; D012503:Saponins; D013778:Tetrazolium Salts; D009249:NADP; C009591:triphenyltetrazolium; D013385:Succinate Dehydrogenase; D002118:Calcium