Browse > Article
http://dx.doi.org/10.6116/kjh.2012.27.6.131.

Effect of Ginsenoside Rg3 on COX-2 Expression in Brain Tissue of Lipopolysaccharide-Treated Mice  

Choi, Wonik (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University)
Cho, Yong-Deok (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University)
Lee, Joon-Seok (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University)
Shin, Jung-Won (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University)
Kim, Seong-Joon (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University)
Sohn, Nak-Won (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University)
Publication Information
The Korea Journal of Herbology / v.27, no.6, 2012 , pp. 131-137 More about this Journal
Abstract
Objectives : Cyclooxygenase (COX) plays a central role in the inflammatory cascade by converting arachidonic acid into prostaglandin. COX-2 is typically induced by inflammatory stimuli in the majority of tissues, it is responsible for propagating the inflammatory response and thus, considered as the best target for anti-inflammatory drugs. The present study investigated the modulatory effect of ginsenoside Rg3, a principle active ingredient in Panax ginseng, on COX-2 expression in the brain tissue induced by systemic lipopolysaccharide (LPS) treatment in C57BL/6 mice. Methods : Because systemic LPS treatment induces COX-2 expression immediately in the brain, ginsenoside Rg3 was treated orally with doses of 10, 20, and 30 mg/kg at 1 hour before the LPS (3 mg/kg, i.p.) injection. At 4 hours after the LPS injection, COX-2 mRNA was measured by real-time polymerase chain reaction method, COX-2 protein levels were measured by Western blotting. In addition, COX-2 expressions in brain tissue were observed with immunohistochemistry and double immunofluoresence labeling. Results : Ginsenoside Rg3 (20 and 30 mg/kg) significantly attenuates up-regulation of COX-2 mRNA and protein expression in brain tissue at 4 hours after the LPS injection. Moreover, ginsenoside Rg3 (20 mg/kg) significantly reduced the number of COX-2 positive neurons in the cerebral cortex and amygdala. Conclusion : These results indicate that ginsenoside Rg3 plays a modulatory role in neuroinflammation through the inhibition of COX-2 expression in the brain and suggest that ginsenoside Rg3 and ginseng may be effective on neurodegenerative diseases caused by neuroinflammation.
Keywords
Ginsenoside Rg3; COX-2; LPS; neuroinflammation; neurodegenerative disease;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
연도 인용수 순위
1 Qi LW, Wang CZ, Yuan CS. Isolation and analysis of ginseng: advances and challenges. Nat Prod Rep. 2011 ; 28(3) : 467-95.   DOI   ScienceOn
2 Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol. 1999 ; 58 : 1685-93.   DOI   ScienceOn
3 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) : 92-97.   DOI   ScienceOn
4 Kim JH, Cho SY, Lee JH, Jeong SM, Yoon IS, Lee BH, Lee JH, Pyo MK, Lee SM, Chung JM, Kim S, Rhim H, Oh JW, Nah SY. Neuroprotective effects of ginsenoside Rg3 against homocysteine- induced excitotoxicity in rat hippocampus. Brain Res. 2007 ; 1136(1) : 190-9.   DOI   ScienceOn
5 Kim S, Kim T, Ahn K, Park WK, Nah SY, Rhim H. Ginsenoside Rg3 antagonizes NMDA receptors through a glycine modulatory site in rat cultured hippocampal neurons. Biochem Biophys Res Commun. 2004 ; 323(2) : 416-24.   DOI   ScienceOn
6 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
7 Tian J, Zhang S, Li G, Liu Z, Xu B. 20(S)-ginsenoside Rg3, a neuroprotective agent, inhibits mitochondrial permeability transition pores in rat brain. Phytother Res. 2009 ; 23(4) : 486-91.   DOI   ScienceOn
8 Joo SS, Yoo YM, Ahn BW, Nam SY, Kim YB, Hwang KW, Lee do I. Prevention of inflammation-mediated neurotoxicity by Rg3 and its role in microglial activation. Biol Pharm Bull. 2008 ; 31(7) : 1392-6.   DOI   ScienceOn
9 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/interferon-gamma-stimulated BV-2 microglial cells. Planta Med. 2006 ; 72(7) : 627-33.   DOI   ScienceOn
10 O'Banion MK. Cyclooxygenase-2: molecular biology, pharmacology, and neurobiology. Crit Rev Neurobiol. 1999 ; 13(1) : 45-82.   DOI
11 Choi SH, Aid S, Bosetti F. The distinct roles of cyclooxygenase-1 and -2 in neuroinflammation: implications for translational research. Trends Pharmacol Sci. 2009 ; 30(4) : 174-81.   DOI   ScienceOn
12 Minghetti L. Cyclooxygenase-2 (COX-2) in inflammatory and degenerative brain diseases. J Neuropathol Exp Neurol. 2004 ; 63(9) : 901-10.   DOI
13 Chen QJ, Zhang MZ, Wang LX. Gensenoside Rg3 inhibits hypoxia-induced VEGF expression in human cancer cells. Cell Physiol Biochem. 2010 ; 26(6) : 849-58.   DOI   ScienceOn
14 Kim SM, Lee SY, Yuk DY, Moon DC, Choi SS, Kim Y, Han SB, Oh KW, Hong JT. Inhibition of NF-kappaB by ginsenoside Rg3 enhances the susceptibility of colon cancer cells to docetaxel. Arch Pharm Res. 2009 ; 32(5) : 755-65.   DOI   ScienceOn
15 Bae EA, Han MJ, Shin YW, Kim DH. Inhibitory effects of Korean red ginseng and its genuine constituents ginsenosides Rg3, Rf, and Rh2 in mouse passive cutaneous anaphylaxis reaction and contact dermatitis models. Biol Pharm Bull. 2006 ; 29(9) : 1862-7.   DOI   ScienceOn
16 Jeong HK, Jou I, Joe EH. Systemic LPS administration induces brain inflammation but not dopaminergic neuronal death in the substantia nigra. Exp Mol Med. 2010 ; 42(12) : 823-32.   DOI   ScienceOn
17 Kang KS, Kim HY, Yamabe N, Park JH, Yokozawa T. Preventive effect of 20(S)-ginsenoside Rg3 against lipopolysaccharide-induced hepatic and renal injury in rats. Free Radic Res. 2007 ; 41(10) : 1181-8.   DOI   ScienceOn
18 Henry CJ, Huang Y, Wynne AM, Godbout JP. Peripheral lipopolysaccharide (LPS) challenge promotes microglial hyperactivity in aged mice that is associated with exaggerated induction of both pro-inflammatory IL-1beta and anti-inflammatory IL-10 cytokines. Brain Behav Immun. 2009 ; 23(3) : 309-17.   DOI   ScienceOn
19 Chung DW, Yoo KY, Hwang IK, Kim DW, Chung JY, Lee CH, Choi JH, Choi SY, Youn HY, Lee IS, Won MH. Systemic administration of lipopolysaccharide induces cyclooxygenase-2 immunoreactivity in endothelium and increases microglia in the mouse hippocampus. Cell Mol Neurobiol. 2010 ; 30(4) : 531-41.   DOI   ScienceOn
20 Cao C, Matsumura K, Yamagata K, Watanabe Y. Induction by lipopolysaccharide of cyclooxygenase-2 mRNA in rat brain; its possible role in the febrile response. Brain Res. 1995 ; 697(1-2) : 187-96.   DOI   ScienceOn
21 Aid S, Bosetti F. Targeting cyclooxygenases-1 and -2 in neuroinflammation: Therapeutic implications. Biochimie. 2011 ; 93(1) : 46-51.   DOI   ScienceOn
22 Hinz B, Brune K. Cyclooxygenase-2-10 years later. J Pharm Exp Ther. 2002 ; 300 : 367-75.   DOI   ScienceOn
23 Minghetti L. Cyclooxygenase-2 (COX-2) in inflammatory and degenerative brain diseases. J Neuropathol Exp Neurol. 2004 ; 63(9) : 901-10.   DOI
24 Lee EJ, Son GH, Chung S, Lee S, Kim J, Choi S, Kim K. Impairment of fear memory consolidation in maternally stressed male mouse offspring: evidence for nongenomic glucocorticoid action on the amygdala. J Neurosci. 2011 ; 31(19) : 7131-40.   DOI   ScienceOn
25 Wang H, Hitron IM, Iadecola C, Pickel VM. Synaptic and vascular associations of neurons containing cyclooxygenase-2 and nitric oxide synthase in rat somatosensory cortex. Cereb Cortex. 2005 ; 15(8) : 1250-60.   DOI
26 Stefanovic B, Bosetti F, Silva AC. Modulatory role of cyclo- oxygenase-2 in cerebrovascular coupling. Neuroimage. 2006 ; 32(1) : 23-32.   DOI   ScienceOn
27 Hewett SJ, Bell SC, Hewett JA. Contributions of cyclooxygenase-2 to neuroplasticity and neuropathology of the central nervous system. Pharmacol Ther. 2006 ; 112(2) : 335-57.   DOI   ScienceOn
28 Tan H, Lauzon NM, Bishop SF, Chi N, Bechard M, Laviolette SR. Cannabinoid transmission in the basolateral amygdala modulates fear memory formation via functional inputs to the prelimbic cortex. J Neurosci. 2011 ; 31(14) : 5300-12.   DOI   ScienceOn
29 Fischborn SV, Soerensen J, Potschka H. Targeting the prostaglandin E2 EP1 receptor and cyclooxygenase-2 in the amygdala kindling model in mice. Epilepsy Res. 2010 ; 91(1) : 57-65.   DOI   ScienceOn
30 Vidensky S, Zhang Y, hand T, Goellner J, Shaffer A, Isakson P, Andreasson K. Neuronal overexpression of COX-2 results in dominant production of PGE2 and altered fever response. Neuromolecular Med. 2003 ; 3(1) : 15-28.   DOI   ScienceOn
31 Quan N, Whiteside M, Herkenham M. Cyclooxygenase 2 mRNA expression in rat brain after peripheral injection of lipopolysaccharide. Brain Res. 1998 ; 802(1-2) : 189-97.   DOI   ScienceOn