본문 바로가기
HOME> 논문 > 논문 검색상세

논문 상세정보

Ginsenosides attenuate the 3-nitropropioic acid-induced rat striatal degeneration in an age-dependent manner

Kim, Jong-Hoon    (Research Laboratory for the Study of Ginseng Signal Transduction and Dept. of Physiology, College of Veterinary Medicine, Konkuk University   ); Nah, Seung-Yeol    (Research Laboratory for the Study of Ginseng Signal Transduction and Dept. of Physiology, College of Veterinary Medicine, Konkuk University  );
  • 초록

    The number of reporting the effects on ginseng's physiological, pharmacological, and behavioral effects has been increased every year. Major active components of Panax ginseng, are the ginsenosides, which are mainly triterpenoid dammarane derivatives. 3-Nitropropionic acid (3-NP) is blown to induce cellular energy deficit and oxidative stress related neurotoxicity via an irreversible inhibition of the mitochondrial enzyme succinate dehydrogenase (SDH). Intraperitoneal injection of 3-NP produces striatal degeneration. Aged animals was more vulnerable to 3-NP than young animal. We used three different ages of 5-, 8-, and 26-week-old rats. 3-NP alone treatment induced striatal lesion and increased lesion volume with age-dependent manner in 5-, 8-, and 26-week-old rats by $30.2{\pm}5.8$ , $v$ , and $51.3{\pm}8.4mm^3$ , respectively. However, pretreatment of GTS (100 mg/kg/day) before 3-NP reduced striatal lesion in 5-,8-, and 26-week-old rats by $3.15{\pm}6.1$ , $8.89{\pm}1.9$ , and $27.3{\pm}5.6mm^3$ , respectively. Pretreatment of GTS also significantly increased survival rate in 5-week-old rats (3-NP alone: GTS +3-NP = $40.4{\pm}6.3$ : $72.5{\pm}9.5\%$ ) than 8-week-old rats (3-NP alone: GTS + 3-NP : $13.5{\pm}5.2\%$ : $45.1{\pm}3.1\%$ ). In 26-week-old rats, 3-NP alone treated group died on day 18, whereas GTS +3-NP-treated group prolonged lifespan to 30 days. Thus, pretreatment of GTS before administration of 3-NP extended lifespan in all ages. The present results indicate that aged animals are more vulnerable to 3-NP and GTS pretreatment protected 3-NP-induced striatal damage in different ages of animals.


  • 주제어

    Ginseng saponins .   3-Nitropropionic acid .   Striatal degeneration .   Aged animal .   Neuroprotection.  

  • 참고문헌 (37)

    1. Beal, M.P., Brouillet, E., Jenkins, B.G, Ferrante, R.J., Kowall, N.W., Miller, J.M., Storey, E., Srivastava, R., Rosen, B.R. and Hyman, B.T. : Neurochemical and histological characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid. J. Neurosci. 13, 4181-4192 (1993) 
    2. Wullner, A.B., Young, J.B., Penney and M.F. Beal. : 3-Nitropropionic acid toxicity in the striatum. J. Neurochem. 63, 1772-1781 (1994) 
    3. Palfi, R.J., Ferrante, E., Brouillet, M.F., Beal, R., Dolan, M.C., Guyot, M., Peschanski and P. Hantraye. : Chronic 3-nitropropionic acid treatment in baboons replicates the cognitive and motor deficits of Huntington's disease. J Neurosci. 16, 3019-3025 (1996) 
    4. James, L.F., Hartley, W.J., Williams, M.C. and Van Kampen, K.R. : Field and experimental studies in cattle and sheep poisoned by nitro-bearing Astragalus or their toxins. Am. J .Vet. Res. 41, 377-382 (1980) 
    5. Ludolph, A.C., He, F., Spencer, P.S., Hammerstad, land Sabri, M. : 3-Nitropropionic acid B exogenous animal neurotoxin and possible human strital toxin. Can. J. Neurol. 18, 492-498 (1991) 
    6. Borlogan, C.V., Koutouzis, T.K. and Sandberg, P.R. : 3-Nitropropionic acid animal model and Huntington's disease. Neurosci. Biobehav. Rev. 21, 289-293 (1997) 
    7. Brouillet, E., Conde, F., Beal, M.F. and Hantraye, P. : Replicating Huntington's disease phenotype in experimental animals. Prog. Neurobiol. 59,427-468. (1999) 
    8. Alston, T.A., Mela, L. and Bright, H.F. : 3-Nitropropionate, the toxic substance of Indigofera, is a suicide inactivator of succinate dehydrogenase. Proc. Nat'l Acad. Sci. 74, 3767-3771 (1977) 
    9. Coles, C.J., Edmondson, D.E. and Singer, T.P. : Inactivation of succinate dehydrogenase by 3-nitropropionate. J. Biol. Chem. 254, 5161-5167 (1979) 
    10. Pang, Z. and Geddes, J.W.: Mechanisms of cell death induced by the mitochondrial toxin 3-nitropropionic acid: acute excitotoxic necrosis and delayed apoptosis. J. Neurasci. 17, 3064-3073 (1997) 
    11. Novelli, A., Reilly, J.A., Lysko, P.G. and Hennebery, R.C. : Glutamate becomes neurotoxic via the N-methyl-D-aspartate receptor when intracellular energy levels are reduced. Brain Res. 451, 205-212 (1988) 
    12. Zeevalk, G.D. and Nicklas, W.J. : Mechanisms underlying initiation of excitatoxicity associated with metabolic inhibition. J. Pharmacol. Exp. Ther. 257, 870-878 (1991) 
    13. Deshpande, S.B., Fukuda, A. and Nishino, H. : 3-Nitropropionic acid increases the intracellular, $Ca^{2+}$ in cultured astrocytes by reverse operation of the $Na^+$ -$Ca^{2+}$ exchanger. Exp. Neurol. 145, 38-45 (1997) 
    14. Calabresi, P., Gubellini, P., Picconi, B., Centonze, D., Pisani, A., Bonsi, Greengard P., Hipskind, R.A., Borrelli, E. and Bernardi, G. : Inhibition of mitochondrial complex II induces a long-term potentiation of NMDA-mediated synaptic excitation in the striatum requiring endogenous dopamine. J. Neurosci. 21, 5110-5120 (2001) 
    15. Nasr, P., Gursahani, H.I., Pang, Z., Bondada, V., Lee, L, Hadley, R.W. and Geddes, J.W. : Influence of cytosolic and mitochondrial cc, ATP, mitochondrial membrane potential, and calpain activity on the mechanism of neuron death induced by 3-nitropropionic acid. Neurochem. International. 43, 89-99 (2003) 
    16. Brouillet, E., Jenkins, B.G, Hyman, B.T., Ferrante, R.J., Kowall, N.W., Srivastava, R., Roy, D.S., Rosen, B.R. and Beal, M.F. : Age-dependent vulnerability of the striatum to the mitochondrial toxin 3-nitropropionic acid. J. Neurochem. 60, 356-359 (1993) 
    17. Nah, S.Y. : Ginseng; Recent advances and Trends. J Ginseng Res. 21,1-12 (1997) 
    18. Nah, S.Y., Park, H.J. and McCleskey, E.W. : A trace component of ginseng that inhibits $Ca^{2+}$ channels through a pertussis toxin-sensitive G protein. Proc. Natl. Acad. Sci. 92, 8739-8743 (1995) 
    19. Kim, H.S., Lee, J.H., Koo, Y.S. and Nah, S.Y. : Effects of ginsenosides on Ca2+ channels and membrane capacitance in rat adrenal chromaffin cells. Brain Res. Bull. 46, 245-251 (1998a) 
    20. Rhim, H., Kim, H., Lee, D.Y., Oh, T.H. and Nah, S.Y. : Ginseng and gins enos ide Rg3, a newly identified active ingredient of ginseng, modulate $Ca^{2+}$ channel currents in rat sensory neurons. Eur. J. Pharmacol. 436, 151-158 (2002) 
    21. Kim, Y.C., Kim, S.R., Markelonis, G.J. and Oh, T.H. : Ginsenosides $Rb_1$and Rg_3$ protect cultured rat cortical cells from glutamate-induced neurodegeranation. J. Neurosci. Res. 53, 426-432 (1998b) 
    22. Kim, S., Ahn, K., Oh, T.H., Nah, S.Y. and Rhim, H. : Inhibitory effect of ginsenosides on NMDA receptor-mediated signals in rat hippocampal neurons. Biochem. Biophys. Res. Commun. 296, 247-254 (2002) 
    23. Chu, G.X. and Chen, X. : Anti-lipid peroxidation and protection of ginsenosides against cerebral ischemia-reperfusion injury of rats. Acta Pharma. Sin. 11, 119-123 (1990) 
    24. Liao, B., Newmark, H. and Zhou, R. : Neuroprotective effects of ginseng total saponin and ginsenosides Rb1 and Rg1 on spinal cord neurons in vitro. Exp. Neurol. 173, 224-234 (2002) 
    25. Kampen, J.V., Robertson, H., Hagg, T. and Drobitch, R. : Neuroprotective actions of the ginseng extract G115 in two redent models of Parkinson's disease. Exp. Neurol. 184, 521529 (2003) 
    26. Radad, K., Gille, G., Moldzio, R., Saito, H., Ishge, K. and Rausch, W.D. : Ginsenoside Rb1 and Rg1 effects on survival and neurite growth of $MPP^+$-affected mesencephalic dopaminergic cells. J. Neural Transmission. 111, 37-45 (2004) 
    27. Kim, J.H., Kim, S., Yoon, I.S., Lee, J.H., Jang, B.J., Jeong, S.M., Lee, J.H., Lee, B.H., Han, J.S., Oh, S., Kim, H.C., Park, T.K., Rhim, H. and Nah, S.Y. : Protective effects of ginseng saponins on 3-nitropropionic acid-induced striatal degeneration in rats. Neuropharmacoogy 48, 743-756 (2005) 
    28. O'Conner, J.L, and Kellom, T.A. : Ether as an anesthetic for decapitation in the rat gonadotropin secretion by subsequently established anterior pituitary cell cultures : Proc. Soc. Exp. Biol. Med. 190, 320-323 (1989) 
    29. Chu, G.X. and Chen, X. : Protective effect of ginsenosides on acute cerebral ischemia-reperfusion injury of rats. China. J. Pharmacol. Toxicol. 3. 18-23 (1989) 
    30. Lee, W.T., Yin, H.S. and Shen, Y.Z. : The mechanism of neuronal death produced by mitochondrial toxin 3-nitropropionic acid: the role of N-methyl-D-aspartate glutamate receptors and mitochondrial calcium overload. Neuroscience 112, 707-716. (2002b) 
    31. Guyot, M.C., Palfi, S., Stuzmann, J.M., Maziere, M., Hantraye, P. and Brouillet, E. : Riluzole protects from motor deficits and striatal degeneration produced by systemic 3-nitropropionic acid intoxication in rats. Neuroscience 81, 141-149 (1997) 
    32. Jeong, S.M., Lee, J.H., Kim, S., Rhim, H., Lee, B.H., Kim, J.H., Oh, J.H., Lee, S.M. and Nah, S.Y. : Ginseng saponins induce store-operated calcium entry in Xenopus oocytes. Br. J. Pharmacol. 142, 585-593 (2004) 
    33. Nah, S.Y. and McCleskey, E.W. : Ginseng root extract inhibits calcium channels in rat sensory neurons through a similar path, but different receptor, as type opioids. J Ethnopharmacol. 42, 45-51 (1994) 
    34. Lee, J.H., Kim. S.H., Kim, D., Hong, H.N. and Nah, S.Y. : protective effect of ginsenosides, active ingredients of Panax ginseng, on kainate-induced neurotoxicity in rat hippocampus. Neurosci. Lett. 325, 129-133 (2002a) 
    35. Ming, L. : Moldy sugarcane poisoning-a case report with a brief review. Clin. Toxicol. 33, 363-367 (1995) 
    36. Maragos, W.F., Tillman, P.A., Chesnut, M.D., Jakel, R.J. : Clorgyline and deprenyl attenuate striatal malonate and 3- nitropropionic acid lesions. Brain Res. 834, 168-172 (1999) 
    37. Fukuda, A., Deshpande, S.B., Shimano, Y. and Nishino, H. : Astrocytes are more vulnerable than neurons to cellular $Ca^{2+}$ overload induced by a mitochondrial toxin, 3-nitropropionic acid. Neurosci. 87, 497-507 (1998) 

 저자의 다른 논문

  • Nah, Seung-Yeol (29)

    1. 2003 "홍삼사포닌이 좌골신경 재생에 미치는 영향" Journal of ginseng research = 高麗人參學會誌 27 (3): 103~109    
    2. 2003 "Differential Effect of Bovine Serum Albumin on Ginsenoside Metabolite-Induced Inhibition of ${\alpha}3{\beta}4$ Nicotinic Acetylcholine Receptor Expressed in Xenopus Oocytes" Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea 26 (10): 868~873    
    3. 2005 "Effects of Ginsenoside Total Saponins on Experimental Irritable Bowel Syndrome in Rats" Journal of ginseng research = 高麗人參學會誌 29 (2): 94~99    
    4. 2005 "Effects of Korean Red Ginseng Extract on Cisplatin-Induced Nausea and Vomiting" Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea 28 (6): 680~684    
    5. 2005 "Effects of Ginsenoside Rg3 Epimers on Swine Coronary Artery Contractions" Journal of ginseng research = 高麗人參學會誌 29 (3): 119~125    
    6. 2005 "Xenopus laevis oocytes에서 진세노사이드에 의하여 활성화되는 Ca2+-activated Cl- 이온 통로의 유전자 클로닝, 조직 분포 및 채널 특성" Journal of ginseng research = 高麗人參學會誌 29 (4): 167~175    
    7. 2005 "Antimicrobial, Anti-inflammatory, and Anti-oxidative Effects of Water- and Ethanol-extracted Brazilian Propolis" Food science and biotechnology 14 (4): 474~478    
    8. 2005 "Effect of Calmodulin on Ginseng Saponin-Induced $Ca^{2+}$-Activated $Cl^{-}$ Channel Activation in Xenopus laevis Oocytes" Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea 28 (4): 413~420    
    9. 2005 "Ginseng and ion channels: Are ginsenosides, active component of Panax ginseng, differential modulator of ion channels?" Journal of ginseng research = 高麗人參學會誌 29 (1): 19~26    
    10. 2005 "The Inhibitory Effects of Korean Red Ginseng Saponins on 5- HT3A Receptor Channel Activity Are Coupled to Anti-Nausea and Anti-Vomiting Action" Journal of ginseng research = 高麗人參學會誌 29 (1): 37~43    

 활용도 분석

  • 상세보기

    amChart 영역
  • 원문보기

    amChart 영역

원문보기

무료다운로드
  • NDSL :
유료다운로드

유료 다운로드의 경우 해당 사이트의 정책에 따라 신규 회원가입, 로그인, 유료 구매 등이 필요할 수 있습니다. 해당 사이트에서 발생하는 귀하의 모든 정보활동은 NDSL의 서비스 정책과 무관합니다.

원문복사신청을 하시면, 일부 해외 인쇄학술지의 경우 외국학술지지원센터(FRIC)에서
무료 원문복사 서비스를 제공합니다.

NDSL에서는 해당 원문을 복사서비스하고 있습니다. 위의 원문복사신청 또는 장바구니 담기를 통하여 원문복사서비스 이용이 가능합니다.

이 논문과 함께 출판된 논문 + 더보기