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http://dx.doi.org/10.5142/JGR.2004.28.2.120

White Ginseng Saponin Upregulated the Production of -TNFTNF-α, IL-1β and NO in Primary Cultures of Mixed Glial Cells  

성정훈 (고려대학교 의과대학 약리학교실)
최동희 (고려대학교 의과대학 약리학교실)
김동훈 (고려대학교 의과대학 약리학교실)
전보권 (고려대학교 의과대학 약리학교실)
최상현 (고려대학교 의과대학 약리학교실)
Publication Information
Journal of Ginseng Research / v.28, no.2, 2004 , pp. 120-126 More about this Journal
Abstract
Glial cells such as astrocytes and microglial cells are the main source of proinflammatory cytokines and nitric oxide(NO) in the central nervous system, which exert neuroimmune and inflammatory functions and other various neurobiologic effects. Though Panax ginseng C.A. Meyer has been known to strengthen the body's defence mechanisms and also to maintain the homeostasis in the central nervous system, the effects of Panax ginseng on the production of immune and inflammatory mediators have not been studied well in the brain. Therefore, this study was designed to study the effects of ginseng saponins on the production of proinflammatory cytokines and NO in the primary cultures of mixed glial cells. White ginseng saponin, 200-500 $\mu$g/ml, showed significant cytotoxicity after 72 hrs and increased TNF-$\alpha$, IL-$\beta$, and NO production. Lower doses of 50-100 $\mu\textrm{g}$/ml showed little cytotoxicity until 72 hrs and also increased the production of TNF-$\alpha$, IL-1$\beta$, and NO. Triple immune staining showed that white ginseng saponin, 200$\mu\textrm{g}$/ml for 72 ks, induced stellation of astrocytes and iNOS expression exclusively in microglial cells. Taken together, the white ginseng saponin increased the production of proinflammatory cytokines such as TNF-$\alpha$ and IL-1$\beta$, and induced iNOS expression and NO production in mixed glial cell cultures, which may be ascribed to the enhancement of central immune responses and the regulation of inflammatory reactions by Panax ginseng.
Keywords
white ginseng saponin; astrocytes; microglial cells; TNF-$\alpha$; IL-1$\beta$nitric oxide;
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1 Gillis, C. N. : Panax ginseng pharmacology: a nitric oxide link? Biochem. Pharmacol. 54, 1-8 (1997)   DOI   ScienceOn
2 McCarthy, K. D. and de Vellis, J.: Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue. J. Cell Biol. 85, 890-902 (1980)   DOI   ScienceOn
3 Giulian, D. and Baker, T. J.: Characterization of ameboid microglia isolated from developing mammalian brain. J. Neurosci. 6, 2163-2178 (1986)
4 Ramakers, G. J. A. and Moolenaar, W. H. : Regulation of astrocyte morphology by RhoA and lysophosphatidic acid. Exp. Cell Res. 245, 252-262 (1998)   DOI   ScienceOn
5 Cechin, S. R., Gottfried, C., Prestes, C. C., Wofchuk, S. T., Andrighetti, L. and Rodnight, R. : Astrocyte stellation in saline media lacking bicarbonate: possible relation to intracellular pH and tyrosine phosphorylation. Brain Res. 946, 12-23 (2002)   DOI   ScienceOn
6 Eng, L. F. and Ghirnikar, R. S. : GFAP and astrogliosis. Brain Pathol. 4, 229-237 (1994)   DOI   ScienceOn
7 Norton, W. T., Aquino, D. A., Hozuni, I., Chiu, F. C. and Brosnan, C. F. : Quantitative aspects of reactive gliosis: a review. Neurochem. Res. 17, 877-885 (1992)   DOI
8 Norenberg, M. D.: Immunology of the nervous system. p.173-199. Oxford University Press, New York (1997)
9 Perry, V. H. and Gordon, S.: Immunology of the nervous system. p.155-172. Oxford University Press, New York (1997)
10 Benveniste, E. N.: Immunology of the nervous system. p.419-459. Oxford University Press, New York (1997)
11 Benveniste, E. N.: Cytokine actions in the central nervous system. Cytokine Growth Factor Rev. 9, 259-275 (1998)   DOI   ScienceOn
12 Murphy, S., Simmons, M. L., Agullo, L., Garcia, A., Feinstein, D. L., Galea, E., Reis, D. J., Minc-Golomb, D. and Schwartz, J. P.: Synthesis of nitric oxide in CNS glial cells. Trends Neurosci. 16, 323-328 (1993)   DOI   ScienceOn
13 Chen, X. : Cardiovascular protection by ginsenosides and their nitric oxide releasing action. Clin. Exp. Pharmacol. Physiol. 23, 728-732 (1996)   DOI   ScienceOn
14 Kim, N. D., Kang, S. Y., Park, J. H. and Schini-Kerth, V. B. : Ginsenoside $Rg_3$ mediates endothelium-dependent relaxation in response to ginsenosides in rat aorta: role of $K^+$ channels. Eur. J. Pharmacol. 367, 41-49 (1999)   DOI   ScienceOn
15 Ndkajima, S., Uchiyama, Y., Yoshida, K., Mizukawa, H. and Haruki, E. : The effects of ginseng radix rubra on human vascular endothelial cells. Am. J. Chin. Med. 26, 365-373 (1998)   DOI   ScienceOn
16 Kang, S. Y., Schini-Kerth, V. B. and Kim, N. D. : Ginsenosides of the protopanaxatriol group cause endothelium-dependent relaxation in the rat aorta. Life Sci. 56, 1577-1586 (1995)   DOI   ScienceOn
17 Ventura, R. and Harris, K. M.: Three-dimensional relationships between hippocampal synapses and astrocytes. J. Neurosci. 19, 6897-6906 (1999)
18 Gasser, U. E. and Hatten, M. E. : Neuron-glia interactions of rat hippocampal cells in vitro: glial-guided neuronal migration and neuronal regulation of glial differentiation. J. Neurosci. 10, 1276-1285 (1990)
19 Mi, H., Haeberle, H. and Barres, B. A. : Induction of astrocyte differentiation by endothelial cells. J. Neurosci. 21, 1538-1547 (2001)
20 Mason, C. A., Edmondson, J. C. and Hatten, M. E. : The extending astroglial process: development of glial cell shape, the growing tip, and interactions with neurons. J. Neurosci. 8, 3124-3134 (1988)
21 Janzer, R. C. and Raff, M. C. : Astrocytes induce blood-brain barrier properties in endothelial cells. Nature 325, 253-257 (1987)   DOI   ScienceOn
22 Park, Y. C., Lee, C. H., Kang, H. S., Kim, K. W., Chung, H. T. and Kim, H. D. : Ginsenoside-$Rh_1$ and $Rh_2$ inhibit the induction of nitric oxide synthesis in murine peritoneal macrophages. Biochem. Mol. Biol. Int. 40, 751-757 (1996)
23 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 neurodegeneration. J. Neurosci. Res. 53, 426-432 (1998)   DOI   ScienceOn
24 Chen, X., Salwinski, S. and Lee, T. J. : Extracts of Ginkgo biloba and ginsenosides exert cerebral vasorelaxation via a nitric oxide pathway. Clin. Exp. Pharmacol. Physiol. 24, 958-959 (1997)   DOI   ScienceOn
25 Fan, Z. H., Isobe, K., Kiuchi, K. and Nakashima, I. : Enhancement of nitric oxide production from activated macrophages by a purified form of ginsenoside $(Rg_1)$. Am. J. Chin. Med. 23, 279-287 (1995)   DOI   ScienceOn
26 Isobe, I., Maeno, Y., Nagao, M., Iwasa, M., Koyama, H., Seko-Nakamura, Y. and Monma-Ohtaki, J. : Cytoplasmic vacuolation in cultured rat astrocytes induced by an organophosphorus agent requires extracellular signal-regulated kinase activation. Toxicol. Appl. Pharmacol. 193, 383-392 (2003)   DOI   ScienceOn
27 Possel, H., Noack, H., Putzke, J., Wolf, G. and Sies, H. : Selective upregulation of inducible nitric oxide synthase(iNOS) by lipopolysaccharide(LPS) and cytokines in microglia: in vitro and in vivo studies. Glia 32, 51-59 (2000)   DOI   ScienceOn
28 Kim, H., Chen, X., Gillis, C. N. : Ginsenosides protect pulmonary vascular endothelium against free radical-induced injury. Biochem. Biophys. Res. Commun. 189, 670-676 (1992)   DOI   ScienceOn
29 Choi, S. H., Choi, D. H., Song, K. S., Shin, K. H. and Chun, B. G. : Zaprinast, an inhibitor of cGMP-selective phosphodiesterases, enhances the secretion of TNF-alpha and IL-Ibeta and the expression of iNOS and MHC class II molecules in rat microglial cells. J. Neurosci. Res. 67, 411-421 (2002)   DOI   ScienceOn
30 Jeon, B. H., Kim, C. S., Kim, H. S., Park, J. B. Nam, K. Y. and Chang, S. J. : Effect of Korean red ginseng on blood pressure and nitric oxide production. Acta. Pharmacol. Sin. 21, 1095-1100 (2000)
31 Han, S. W. and Kim, H. : Ginsenosides stimulate endogenous production of nitric oxide in rat kidney. Int. J. Biochem. Cell Biol. 28, 573-580 (1996)   DOI   ScienceOn
32 Sonoda, Y., Kasahara, T., Mukaida, N., Shimizu, N., Tomoda, M. and Takeda, T. : Stimulation of interleukin-8 production by acidic polysaccharides from the root of Panax ginseng. Immunopharmacology 38, 287-294 (1998)   DOI   ScienceOn
33 Kim, D. H., Jung, J. S., Suh, H. W., Huh, S. O., Min, S. K., Son, B. K., Park, J. H., Kim, N. D., Kim, Y. H. and Song, D. K. : Inhibition of stress-induced plasma corticosterone levels by ginsenosides in mice: involvement of nitric oxide. Neuroreport 9, 2261-2264 (1998)   DOI   ScienceOn
34 Kim, K. H., Lee, Y. S., Jung, I. S., Park, S. Y., Chung, H. Y., Lee, I. R. and Yun, Y. S. : Acidic polysaccharide from Panax ginseng, ginsan, induces Th1 cell and macrophage cytokines and generates LAK cells in synergy with rIL-2. Planta Med. 64, 110-115 (1998)   DOI   ScienceOn
35 Lee, Y. S., Chung, I. S., Lee, I. R., Kim, K. H., Hong. W. S. and Yun, Y. S. : Activation of multiple effector pathways of immune system by the antineoplastic immunostimulator acidic polysaccharide ginsan isolated from Panax ginseng. Anticancer Res. 17, 323-331 (1997)
36 Cho, S. H., Choi, S. H., Choi, J. W., Kim, D. H., Shin, K. H., Chun, Y. S. and Chun, B. G. : Effect of Panax ginseng on latency of passive avoidance response and neuronal damage of hippocampus. Korea J. Physiol. Pharmacol. 1, 345-353 (1997)
37 Yun, Y. S., Lee, Y. S., Jo, S. K. and Jung, I. S. : Inhibition of autochthonous tumor by ethanol insoluble fractin from Panax ginseng as an immunomodulator. Planta Med. 59, 521-524 (1993)   DOI   ScienceOn
38 Murphy, S. : Production of nitric oxide by glial cells: regulation and potential roles in the CNS. Glia 29, 1-13 (2000)   DOI   ScienceOn