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Potential Effects of Microglial Activation Induced by Ginsenoside Rg3 in Rat Primary Culture: Enhancement of Type A Macrophage Scavenger Receptor Expression  

Joo, Seong-Soo (Department of Immunology, College of Pharmacy, Chung-Ang University)
Lee, Do-Ik (Department of Immunology, College of Pharmacy, Chung-Ang University)
Publication Information
Archives of Pharmacal Research / v.28, no.10, 2005 , pp. 1164-1169 More about this Journal
Abstract
Brain microglia are phagocytic cells that are the major inflammatory response cells of the central nervous system and widely held to play important pathophysiologic roles in Alzheimer's disease (AD) in both potentially neurotoxic responses and potentially beneficial phagocytic responses. In the study, we examined whether ginsonoside Rg3, a by-product of red ginseng, enhances the microglial phagocytosis of $A{\beta}$. We found that Rg3 promoted $A{\beta}$ uptake, internalization, and digestion. Increased maximal $A{\beta}$ uptake was observed at 4 and 8 h after Rg3 pretreatment (25 ${\mu}g/mL$), and the internalized $A{\beta}$ was almost completely digested from cells within 36 h when pretreated with Rg3 comparing with single non-Rg3-treated groups. The expression of MSRA (type A MSR) was also up-regulated by Rg3 treatment in a dose- and time-dependent manner which was coincidently identified in western blots for MSRA proteins in cytosol. These results indicate that microglial phagocytosis of $A{\beta}$ may be enhanced by Rg3 and the effect of Rg3 on promoting clearance of $A{\beta}$ may be related to the MSRA-associated action of Rg3. Thus, stimulation of the MSRA might contribute to the therapeutic potentials of Rg3 in microglial phagocytosis and digestion in the treatment of AD.
Keywords
Microglia; Macrophage scavenger receptor; Ginsenoside Rg3; Alzheimer's disease;
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1 Chung, H., Brazil, M., Soe, T. T., and Maxfield, F. R., Uptake, degradation, and release of fibrillar and soluble forms of Alzheimer's amyloid beta-peptide by microglial cells. J. Biol. Chem., 274, 32301-32308 (1999)   DOI
2 Giulian, D., Corpuz, M., Chapman, S., Mansouri, M., and Robertson, C., Reactive mononuclear phagocytosis release neurotoxins after ischemic and traumatic injury to the central nervous system. J. Neurosci. Res., 36, 681-693 (1993)   DOI   ScienceOn
3 Hailer, N. P., Wirjatijasa, F., Roser, N., Hischebeth, G. T., Kort, H. W., and Dehghani, F., Astrocytic factors protect neuronal integrity and reduce microglial activation in an in vitro model of N-methyl-D-aspartate-induced excitotoxic injury in organotypic hippocampal slice cultures. Eur. J. Neurosci., 14, 315-326 (2001)   DOI   ScienceOn
4 Kreutzberg, G. W., Microglia: a senior for pathological events in the CNS. Trends Neurosci., 19, 312-318 (1996)   DOI   PUBMED   ScienceOn
5 Paresce, D. M., Chung, H. -C., and Maxfield, F. R., Slow degradation of aggregates of the Alzheimer's disease amyloid a-protein by microglial cells. J. Biol. Chem., 272, 29390-29397 (1997)   DOI   ScienceOn
6 Shibata S., Chemistry and cancer preventing activities of ginseng saponins and some related triterpenoid compounds. J. Korean Med. Sci., 16, S28-S37 (2001)
7 Singh, V. K., Agarwal, S. S., and Gupta, B. M., Immunomo-dulatory activity of Panax ginseng extract. Planta Med., 50, 462-465 (1984)   DOI   ScienceOn
8 Wagner, H., Norr, H., and Winterhoff, H., Plant adaptogens. Phytomedicine, 1, 63-76 (1994)   DOI
9 Kopec, K. K. and Carroll, R. T., Alzheimer's $\beta$-amyloid peptide 1-42 induces a phagocytic response in murine microglia. J. Neurochem., 71, 2123-2131 (1998)   DOI   ScienceOn
10 Giulian, D., Li, J., Bartel, S., Broker, J., Li, X., and Kirkpatric, J. B., Cell surface morphology identifies microglia as a distinct class of mononuclear phagocyte. J. Neurosci., 15, 7712-7726 (1995)
11 Tsang, D., Yeung, H. -W., Tso, W. -W., and Peck, H., Ginseng saponins: Influence on neurotransmitter uptake in rat brain synaptosomes. Planta Med., 3, 221-224 (1985)   DOI
12 Dickson, D. W., The pathogenesis of senile plaques. J. Neuropath. Exp. Neur., 56, 321-338 (1997)   DOI   PUBMED   ScienceOn
13 Husemann, J., Loike, J. D., Anakov, R., Febbraio, M., and Silverstein, S. C., Scavenger receptors in neurobiology and neuropathology: their role on microglia and other cells of the nervous system. Glia, 40, 105-205 (2002)
14 Frackowiak, J., Wisniewski, H. M., Wegiel, J., Merz, G. S., Iqbal, K., and Wang, K. -C., Ultrastructure of the microglia that phagocytose amyloid and the microglia that produce betaamyloid fibrils. Acta Neuropathol., 84, 225-233 (1992)   DOI
15 Kitamura, Y., Tanihuchi, T., and Shimohama, S., Apoptotic cell death in neurons and glial cells: Implications for Alzheimer's disease. Jpn. J. Pharmacol., 79, 1-5 (1999)   DOI   ScienceOn
16 Mcgeer, P. L., Akiyama, H., Kawamata, T., Yamada, T., Walker, D. G., and Ishii, T., Immunohistochemical localization of B-amyloid precursor protein sequences in Alzheimer and normal brain tissue by light and electron microscopy. J. Neurosci. Res., 31, 428-442 (1992)   DOI   ScienceOn
17 Paresce, D. M., Ghoshi, R., and Maxfield, F. R., Microglial cells internalize aggregates of the Alzheimer's disease amyloid beta-protein via a scavenger receptor. Neuron, 17, 553-565 (1996)   DOI   ScienceOn
18 Lorton, D., Schaller, J., Lala, A., and De Nardin, E., Chemotactic-like receptors and abeta peptides induced responses in Alzheimer's disease. Neurobial. Aging, 21, 463-473 (2000)   DOI   ScienceOn
19 Rogers, J., Strohmeyer, R., Kovelowski, C. J., and Li, R., Microglia and inflammatory mechanisms in the clearance of amyloid $\beta$ peptides. Glia, 40, 260-269 (2002)   DOI   ScienceOn
20 Yan, S. -D., Zhu, H., Fu, J., Yan, S. -F., Roher, A., Tourtellotte, W. W., Rajavashisth, T., Chen, X., Godman, G. C., Stern, D., and Schmidt, A. M., Amyloid-beta peptide-receptor for advanced glycation endproduct interaction elicits neuronal expression of macrophage-colony stimulating factor: a proinflammatory pathway in Alzheimer disease. Proc. Natl. Acad. Sci. U.S.A., 94, 5296-5301 (1997)   DOI
21 Phillipson, J. D. and Anderson, L. A., Ginseng-quality, safety and efficacy. Pharmaceut. J., 232, 161-165 (1984)
22 Edelstein-keshet, L. and Spiros, A., Exploring the formation of Alzheimer's disease senile plaques in silico. J. Theor. Biol., 216, 301-326 (2002)   DOI   ScienceOn