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Effects of Ginsenoside Rg3 on Early-stage Inflammatory Response in Spinal Cord Compression of Rodents  

Jeong, Beoul (Dept. of Oriental Rehabilitation Medicine, College of Korean Medicine, Kyung-Hee University)
Lee, Jong-Soo (Dept. of Oriental Rehabilitation Medicine, College of Korean Medicine, Kyung-Hee University)
Publication Information
Journal of Korean Medicine Rehabilitation / v.23, no.2, 2013 , pp. 1-15 More about this Journal
Abstract
Objectives : In present study, we investigated the effects of ginsenoside Rg3 on early-stage inflammatory response in spinal cord compression of rodents. Methods : Spinal cord injury(SCI) was induced by a vascular clip method(30 g, 5 min) on the spinal cord of mice. Rg3 was treated orally at 1 hour prior to the SCI induction. Messenger ribonucleic acid(mRNA) expression of tumor necrosis factor-${\alpha}$(TNF-${\alpha}$), interleukin-1${\beta}$(IL-1${\beta}$), interleukin-6(IL-6) and cyclooxygenase-2(COX-2) was measured by the real-time polymerase chain reaction(RT-PCR). Microglia in the spinal cord tissue, neurophils and COX-2 in the peri-lesion and inducible nitric oxide synthase(iNOS) expression in the ventral horn of SCI induced rats were measured by immunohistochemical stain. Results : 1. Rg3 significantly reduced the mRNA expression of TNF-${\alpha}$, IL-1${\beta}$, and COX-2 in the spinal cord tissue compared with SCI group(p<0.05, p<0.01). 2. Rg3 significantly reduced the total number of activated microglia and proportion of phagocytic form in the total activated microglia compared with SCI group(p<0.05, p<0.01). 3. Rg3 significantly reduced myeloperoxidase(MPO) positive neurophil in the peri-lesion compared with SCI group(p<0.05). 4. Rg3 reduced the COX-2 expression in the tissue and motor neurons compared with SCI group. 5. Rg3 significantly reduced iNOS positive motor neurons in the ventral horn compared with SCI group(p<0.01). Conclusions : In conclusion, we demonstrated at first that treatment of ginsenoside Rg3 could reduce significantly the levels of inflammatory mediators in a spinal cord compression model of rodents. Therefore, these results suggested that ginsenoside Rg3 may be a useful antimiflamatory therapeutic candidate for SCI.
Keywords
Ginsenoside Rg3; Early-stage inflammatory response; Spinal cord injury;
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1 Anderberg L, Aldskogius H, Holtz A. Spinal cord injury-scientific challenges for the unknown future. Ups J Med Sci. 2007;112(3): 259-88.   DOI   ScienceOn
2 Beattie MS, Hermann GE, Rogers RC, Bresnahan JC. Cell death in models of spinal cord injury. Prog Brain Res. 2002;137:37-47.   DOI
3 Springer JE, Azbill RD, Knapp PE. Activation of the caspase-3 apoptotic cascade in traumatic spinal cord injury. Nat Med. 1999;5(8):943-6.   DOI   ScienceOn
4 Skaper SD, Leon A. Monosialogangliosides, neuroprotection, and neuronal repair processes. J Neurotrauma. 1992;9(l2):507-16.
5 Pannu R, Barbosa E, Singh AK, Singh I. Attenuation of acute inflammatory response by atorvastatin after spinal cord injury in rats. J Neurosci Res. 2005;79:340-50.   DOI   ScienceOn
6 Schnell L, Fearn S, Schwab ME, Perry VH, Anthony DC. Cytokine-induced acute inflammation in the brain and spinal cord. J Neuropathol Exp Neurol. 1999;58:245-54.   DOI   ScienceOn
7 Campbell SJ, Wilcockson DC, Butchart AG, Perry VH, Anthony DC. Altered chemokine expression in the spinal cord and brain contributes to differential interleukin-1betainduced neutrophil recruitment. J Neurochem. 2002;83:432-41.   DOI   ScienceOn
8 Popovich PG, Wei P, Stokes BT. Cellular inflammatory response after spinal cord injury in Sprague-Dawley and Lewis rats. J Comp Neurol. 1997;377:443-64.   DOI   ScienceOn
9 Yang L, Blumbergs PC, Jones NR, Manavis J, Sarvestani GT, Ghabriel MN. Early expression and cellular localization of proinflammatory cytokines interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in human traumatic spinal cord injury. Spine. 2004;29:966-71.   DOI   ScienceOn
10 Town T, Nikolic V, Tan J. The microglial "activation" continuum: from innate to adaptive responses. J Neuroinflammation. 2005;2:24.   DOI   ScienceOn
11 Vane JR, Bakhle YS, Botting RM. Cyclooxygenases 1 and 2. Annu Rev Pharmacol Toxicol. 1998;38:97-120.   DOI   ScienceOn
12 Vanegas H, Schaible HG. Prostaglandins and cyclooxygenases in the spinal cord. Prog Neurobiol. 2001;64:327-63.   DOI   ScienceOn
13 Hamada Y, Ikata T, Katoh S, Tsuchiya K, Niwa M, Tsutsumishita Y, Fukuzawa K. Role of nitric oxide in compression injury of rat spinal cord. Free Radic Biol Med. 1996;20:1-9.   DOI   ScienceOn
14 Nakahara S, Yone K, Setoguchi T, Yamaura I, Arishima Y, Yoshino S, Komiya S. Changes in nitric oxide and expression of nitric oxide synthase in spinal cord after acute traumatic injury in rats. J Neurotrauma. 2002;19:1467-74.   DOI   ScienceOn
15 Choi KT. Botanical characteristics, pharmacological effects and medicinal components of Korean Panax ginseng C A Meyer. Acta Pharmacol Sin. 2008;29(9):1109-18.   DOI   ScienceOn
16 Bae EA, Hyun YJ, Choo MK, Oh JK, Ryu JH, Kim DH. Protective effect of fermented red ginseng on a transient focal ischemic rats. Arch Pharm Res. 2004;27(11):1136-40.   DOI   ScienceOn
17 Joo SS, Yoo YM, Ahn BW, Nam Ssy, Kim YB, Hwang KW. Prevention of inflammationmediated neurotoxicity by Rg3 and its role in microglial activation. Biol Pharm Bull. 2008;31(7):1392-6.   DOI   ScienceOn
18 Bae EA, Kim EJ, Park JS, Kim HS, Ryu JH, Kim DH. Ginsenosides Rg3 and Rh2 inhibit the activation of AP-1 and protein kinase A pathway in lipopolysaccharide/interferongamma- stimulated BV-2 microglial cells. Planta Med. 2006;72(7):627-33.   DOI   ScienceOn
19 Kim S, Nah SY, Rhim H. Neuroprotective effects of ginseng saponins against L-type Ca2+ channel-mediated cell death in rat cortical neurons. Biochem Biophys Res Commun. 2008;365(3):399-405.   DOI   ScienceOn
20 Tian J, Fu F, Geng M, Jiang Y, Yang J, Jiang W, Wang C, Liu K. Neuroprotective effect of 20(S)-ginsenoside Rg3 on cerebral ischemia in rats. Neurosci Lett. 2005;374(2): 92-7.   DOI   ScienceOn
21 Kim JH, Cho SY, Lee JH, Jeong SM, Yoon IS, Lee BH. Neuroprotective effects of ginsenoside Rg3 against homocysteine-induced excitotoxicity in rat hippocampus. Brain Res. 2007;1136(1):190-9.   DOI   ScienceOn
22 성주원, 김기역, 반효정, 신정원, 강희, 김성준, 손낙원. 黃連解毒湯이 척수 압박손상 흰 쥐의 운동기능 장애에 미치는 영향. 한방재활의학과학회지. 2010;20(4):1-15.
23 박원상, 김은석, 신전원, 김범회, 김성준, 강희, 손낙원, 신정원. 狗脊이 흰쥐의 척수압박 에 의한 신경세포 손상에 미치는 영향. 한방재활의학과학회지. 2010;20(2):1-15.
24 김기역. 黃連解毒湯이 척수 압박손상 흰쥐의 iNOS와 COX-2 발현에 미치는 영향. 경희대학교 동서의학대학원 석사학위논문. 2010:1-32.
25 Marques SA, Garcez VF, Del Bel EA, Martinez AM. A simple, inexpensive and easily reproducible model of spinal cord injury in mice: morphological and functional assessment. J Neurosci Methods. 2009;177(1):183-93.   DOI   ScienceOn
26 Ward RE, Huang W, Curran OE, Priestley JV, Michael-Titus AT. Docosahexaenoic acid prevents white matter damage after spinal cord injury. J Neurotrauma. 2010;27(10):1769-80.   DOI   ScienceOn
27 대한정형외과학회. 정형외과학 제 6판. 서울:최신의학사. 2006:994-1005.
28 Wyndaele M, Wyndaele JJ. Incidence, prevalence and epidemiology of spinal cord injury: what learns a worldwide literature survey? Spinal Cord. 2006;44:523-9.   DOI   ScienceOn
29 DeVivo MJ. Causes and costs of spinal cord injury in the United States. Spinal Cord. 1997;35:809-13.   DOI   ScienceOn
30 Barnabe-Heider F, Frisen J. Stem cells for spinal cord repair. Cell Stem Cell. 2008;3:16-24.   DOI   ScienceOn
31 Tator CH, Koyanagi I. Vascular mechanisms in the pathophysiology of human spinal cord injury. J Neurosurg. 1997;86(3):483-92.   DOI   ScienceOn
32 Louro J, Pearse DD. Stem and progenitor cell therapies: recent progress for spinal cord injury repair. Neurol Res. 2008;30:5-16.   DOI   ScienceOn
33 Bunge MB. Novel combination strategies to repair the injured mammalian spinal cord. J Spinal Cord Med. 2008;31:262-69.   DOI
34 Schwab JM, Brechtel K, Mueller CA, Failli V, Kaps HP, Tuli SK, Schluesener HJ. Experimental strategies to promote spinal cord regeneration-an integrative perspective. Prog Neurobiol. 2006;78:91-116.   DOI   ScienceOn
35 Popovich PG, Wei P, Stokes BT. Cellular inflammatory response after spinal cord injury in Sprague-Dawley and Lewis rats. J Comp Neurol. 1997;377(3):443-64.   DOI   ScienceOn
36 Ackery A, Tator C, Krassioukov A. A global perspective on spinal cord injury epidemiology. J Neurotrauma. 2004;21:1355-70.   DOI   ScienceOn
37 Bunge MB. Novel combination strategies to repair the injured mammalian spinal cord. J Spinal Cord Med. 2008;31:262-9.   DOI
38 Lu J, Waite P. Advances in spinal cord regeneration. Spine. 1999;24:926-30.   DOI   ScienceOn
39 BK Kwon, W Tetzlaff. Pathophysiology and pharmacologic treatment of acute spinal cord injury. The Spine Journal. 2004;4(4):451-64.   DOI   ScienceOn
40 정춘근, 김은영, 신정원, 손영주, 이현삼, 정혁상, 손낙원. 청폐사간탕이 당뇨유발 흰쥐의 뇌 허혈손상에 미치는 영향. 대한한의학회지. 2005;26:217-30.
41 강승준, 금현수, 전연이, 이은주, 박치상, 박창국. 석창포가 뇌허혈을 유발시킨 백서에서의 뇌신경 보호효과. 대한한방내과학회지. 2001;22:341-51.
42 강봉주, 조동욱, 홍성길. 저산소상태에서 육미지황원의 뇌신경세포 보호효과에 대한 연구. 한국한의학연구원논문집. 2001;7:115-24.
43 이상인. 본초학. 서울:의약사. 1975:97-8.
44 김호철. 한약약리학. 서울:집문당. 2001:451.