Browse > Article
http://dx.doi.org/10.4062/biomolther.2009.17.1.47

Schizandra chinensis Alkaloids Inhibit Lipopolysaccharide-Induced Inflammatory Responses in BV2 Microglial Cells  

Choi, Min-Sik (Department of Pharmacology, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University)
Kwon, Kyung-Ja (Center for Geriatric Neuroscience Research, IBST, and School of Medicine, Konkuk University)
Jeon, Se-Jin (Department of Pharmacology, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University)
Go, Hyo-Sang (Department of Pharmacology, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University)
Kim, Ki-Chan (Department of Pharmacology, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University)
Ryu, Jae-Ryun (Department of Pharmacology, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University)
Lee, Jong-Min (Center for Geriatric Neuroscience Research, IBST, and School of Medicine, Konkuk University)
Han, Seol-Heui (Center for Geriatric Neuroscience Research, IBST, and School of Medicine, Konkuk University)
Cheong, Jae-Hoon (Department of Pharmacy, Sahmyook University)
Ryu, Jong-Hoon (Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University)
Bae, Ki-Hwan (College of Pharmacy, Chungnam University)
Shin, Chan-Young (Center for Geriatric Neuroscience Research, IBST, and School of Medicine, Konkuk University)
Ko, Kwang-Ho (Department of Pharmacology, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University)
Publication Information
Biomolecules & Therapeutics / v.17, no.1, 2009 , pp. 47-56 More about this Journal
Abstract
Schizandra chinensis (S. chinensis) exhibits a harmless, 'adaptogen-type' effect leading to improvements in mental performance and learning efficacy in brain. Activated microglia contributes to neuronal injury by releasing neurotoxic products, which make it important to regulate microglial activation to prevent further cytological as well as functional brain damage. However, the effect of S. chinensis on microglial activation has not been examined yet. We have investigated the effects of four compounds (Gomisin A, Gomisin N, Schizandrin and Schizandrol A) from S. chinensis on lipopolysaccharide (LPS)-induced microglial activation. In this study, BV2 microglial cells were activated with LPS and the microglial activation was assessed by up-regulation of activation markers such as nitric oxide (NO), reactive oxygen species (ROS), and matrix metalloproteinase-9 (MMP-9). The results showed that all four compounds significantly reduced the intracellular level of ROS, the release of NO and MMP-9 as well as LPS-induced phosphorylation of ERK1/2. These results strongly suggested that S. chinensis may be useful to modulate inflammation-mediated brain damage by regulating microglial activation.
Keywords
Schizandra chinensis; Microglia; Activation; Nitric oxide (NO); Reactive oxygen species (ROS); Matrix metalloproteinase-9 (MMP-9);
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
Times Cited By Web Of Science : 5  (Related Records In Web of Science)
Times Cited By SCOPUS : 5
연도 인용수 순위
1 Chang, L. and Karin, M. (2001). Mammalian MAP kinase signalling cascades. Nature. 410, 37-40   DOI   ScienceOn
2 Nakashima, M. N., Ajiki, K., Nakashima, K. and Takahashi, M. (2003). Possible role of nitric oxide in anxiety following transient cerebral ischemia in mice. J. Pharmacol. Sci. 91, 47-52   DOI
3 Banati, R. B., Daniel, S. E. and Blunt, S. B. (1998). Glial pathology but absence of apoptotic nigral neurons in long-standing Parkinson's disease. Mov. Disord. 13, 221-227   DOI   ScienceOn
4 Beckman, J. S., Beckman, T. W., Chen, J., Marshall, P. A. and Freeman, B. A. (1990). Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci U S A 87, 1620-1624   DOI   ScienceOn
5 Blasi, E., Barluzzi, R., Bocchini, V., Mazzolla, R. and Bistoni, F. (1990). Immortalization of murine microglial cells by a v-raf/v-myc carrying retrovirus. J. Neuroimmunol. 27, 229-237   DOI   ScienceOn
6 Darley-Usmar, V., Wiseman, H. and Halliwell, B. (1995). Nitric oxide and oxygen radicals: a question of balance. FEBS. Lett. 369, 131-135   DOI   ScienceOn
7 del Zoppo, G. J., Milner, R., Mabuchi, T., Hung, S., Wang, X., Berg, G. I. and Koziol, J. A. (2007). Microglial activation and matrix protease generation during focal cerebral ischemia. Stroke. 38, 646-651   DOI   ScienceOn
8 Park, J. S., Woo, M. S., Kim, D. H., Hyun, J. W., Kim, W. K., Lee, J. C. and Kim, H. S. (2007). Anti-inflammatory mechanisms of isoflavone metabolites in lipopolysaccharide-stimulated microglial cells. J. Pharmacol. Exp. Ther. 320, 1237-1245   DOI   ScienceOn
9 Bruhwyler, J., Chleide, E., Liegeois, J.F. and Carreer, F. (1993). Nitric oxide: a new messenger in the brain. Neurosci. Biobehav. Rev. 17, 373-384   DOI   ScienceOn
10 Cuzner, M. L. and Opdenakker, G. (1999). Plasminogen activators and matrix metalloproteases, mediators of extracellular proteolysis in inflammatory demyelination of the central nervous system. J. Neuroimmunol. 94, 1-14   DOI   ScienceOn
11 Fiebich, B. L., Grozdeva, M., Hess, S., Hull, M., Danesch, U., Bodensieck, A. and Bauer, R. (2005). Petasites hybridus extracts in vitro inhibit COX-2 and PGE2 release by direct interaction with the enzyme and by preventing p42/44 MAP kinase activation in rat primary microglial cells. Planta. Med. 71, 12-19   DOI   ScienceOn
12 Gijbels, K., Galardy, R. E. and Steinman, L. (1994). Reversal of experimental autoimmune encephalomyelitis with a hydroxamate inhibitor of matrix metalloproteases. J. Clin. Invest. 94, 2177-2182   DOI   ScienceOn
13 Bocchini, V., Mazzolla, R., Barluzzi, R., Blasi, E., Sick, P. and Kettenmann, H. (1992). An immortalized cell line expresses properties of activated microglial cells. J. Neurosci. Res. 31, 616-621   DOI   ScienceOn
14 Gonzalez-Scarano, F. and Baltuch, G. (1999). Microglia as mediators of inflammatory and degenerative diseases. Annu. Rev. Neurosci. 22, 219-240   DOI   ScienceOn
15 Choi, J. J. and Kim, W. K. (1998). Potentiated glucose deprivation-induced death of astrocytes after induction of iNOS. J. Neurosci. Res. 54, 870-875   DOI   ScienceOn
16 Bornemann, K.D., Wiederhold, K.H., Pauli, C., Ermini, F., Stalder, M., Schnell, L., Sommer, B., Jucker, M. and Staufenbiel, M. (2001). Abeta-induced inflammatory processes in microglia cells of APP23 transgenic mice. Am. J. Pathol. 158, 63-73   DOI   ScienceOn
17 Jung, K., Ha, E., Uhm, Y., Park, H., Kim, M.J., Kim, H., Baik, H., Hong, M., Yang, J. and Yim, S. V. (2007). Suppressive effect by Hizikia fusiforme on the production of tumor necrosis factor in BV2 murine microglial cells. Neurol. Res. 29, 88-92   DOI   ScienceOn
18 McGeer, P. L. and McGeer, E. G. (2004b). Inflammation and the degenerative diseases of aging. Ann. N. Y. Acad. Sci. 1035, 104-116   DOI   ScienceOn
19 Gloire, G., Legrand-Poels, S. and Piette, J. (2006). NF-kappaB activation by reactive oxygen species: fifteen years later. Biochem. Pharmacol. 72, 1493-1505   DOI   ScienceOn
20 Green, T. R. and Pratt, K. L. (1990). Detection and isolation of the NADPH-binding protein of the NADPH:O2 oxidoreductase complex of human neutrophils. J. Biol. Chem. 265, 19324-19329
21 Guo, L. Y., Hung, T. M., Bae, K. H., Shin, E. M., Zhou, H. Y., Hong, Y. N., Kang, S. S., Kim, H. P. and Kim, Y. S. (2008) Anti-inflammatory effects of schisandrin isolated from the fruit of Schisandra chinensis Baill. Eur. J. Pharmacol. 591, 293-299   DOI   ScienceOn
22 Lu, K., Cho, C. L., Liang, C. L., Chen, S. D., Liliang, P. C., Wang, S. Y. and Chen, H. J. (2007). Inhibition of the MEK/ERK pathway reduces microglial activation and interleukin-1-beta expression in spinal cord ischemia/reperfusion injury in rats. J. Thorac. Cardiovasc. Surg. 133, 934-941   DOI   ScienceOn
23 Gottschall, P. E., Yu, X. and Bing, B. (1995). Increased production of gelatinase B (matrix metalloproteinase-9) and interleukin-6 by activated rat microglia in culture. J. Neurosci. Res. 42, 335-342   DOI   ScienceOn
24 Hung, T. M., Na, M., Min, B. S., Ngoc, T. M., Lee, I., Zhang, X. and Bae, K. (2007). Acetylcholinesterase inhibitory effect of lignans isolated from Schizandra chinensis. Arch. Pharm. Res. 30, 685-690   DOI   ScienceOn
25 Lee, W. J., Shin, C. Y., Yoo, B. K., Ryu, J. R., Choi, E. Y., Cheong, J. H., Ryu, J. H. and Ko, K. H. (2003). Induction of matrix metalloproteinase-9 (MMP-9) in lipopolysaccharidestimulated primary astrocytes is mediated by extracellular signal-regulated protein kinase 1/2 (Erk1/2). Glia. 41, 15-24   DOI   ScienceOn
26 Kim, S. D., Yang, S. I., Kim, H. C., Shin, C. Y. and Ko, K. H. (2007). Inhibition of GSK-3beta mediates expression of MMP-9 through ERK1/2 activation and translocation of NF-kappaB in rat primary astrocyte. Brain. Res. 1186, 12-20   DOI   ScienceOn
27 Hensley, K., Hall, N., Subramaniam, R., Cole, P., Harris, M., Aksenov, M., Aksenova, M., Gabbita, S. P., Wu, J. F., Carney, J. M., Lovell, M., William., Markesbery R., Allan Butterfield, D. (1995). Brain regional correspondence between Alzheimer's disease histopathology and biomarkers of protein oxidation. J. Neurochem. 65, 2146-2156   DOI   ScienceOn
28 Hewett, S. J., Csernansky, C. A. and Choi, D. W. (1994). Selective potentiation of NMDA-induced neuronal injury following induction of astrocytic iNOS. Neuron. 13, 487-494   DOI   ScienceOn
29 Kieseier, B.C., Seifert, T., Giovannoni, G. and Hartung, H.P. (1999). Matrix metalloproteinases in inflammatory demyelination: targets for treatment. Neurology. 53, 20-25   DOI
30 Lau, F. C., Bielinski, D. F. and Joseph, J. A. (2007). Inhibitory effects of blueberry extract on the production of inflammatory mediators in lipopolysaccharide-activated BV2 microglia. J. Neurosci. Res. 85, 1010-1017   DOI   ScienceOn
31 Liang, Y. C., Huang, Y. T., Tsai, S. H., Lin-Shiau, S. Y., Chen, C. F. and Lin, J. K. (1999). Suppression of inducible cyclooxygenase and inducible nitric oxide synthase by apigenin and related flavonoids in mouse macrophages. Carcinogenesis. 20, 1945-1952   DOI   ScienceOn
32 Minghetti, L. and Levi, G. (1998). Microglia as effector cells in brain damage and repair: focus on prostanoids and nitric oxide. Prog. Neurobiol. 54, 99-125   DOI   ScienceOn
33 Semmler, A., Okulla, T., Sastre, M., Dumitrescu-Ozimek, L. and Heneka, M. T. (2005). Systemic inflammation induces apoptosis with variable vulnerability of different brain regions. J. Chem. Neuroanat. 30, 144-157   DOI   ScienceOn
34 Zhao, P., Waxman, S. G. and Hains, B. C. (2007). Extracellular signal-regulated kinase-regulated microglia-neuron signaling by prostaglandin E2 contributes to pain after spinal cord injury. J. Neurosci. 27, 2357-2368   DOI   ScienceOn
35 Lin, S. J., Shyue, S. K., Liu, P. L., Chen, Y. H., Ku, H. H., Chen, J. W., Tam, K. B. and Chen, Y. L. (2004). Adenovirus-mediated overexpression of catalase attenuates oxLDL-induced apoptosis in human aortic endothelial cells via AP-1 and C-Jun N-terminal kinase/extracellular signal-regulated kinase mitogen-activated protein kinase pathways. J. Mol. Cell. Cardiol. 36, 129-139   DOI   ScienceOn
36 McGeer, P. L. and McGeer, E. G. (1995). The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases. Brain. Res. Brain. Res. Rev. 21, 195-218   DOI   ScienceOn
37 McGeer, P. L. and McGeer, E. G. (2004a). Inflammation and neurodegeneration in Parkinson's disease. Parkinsonism. Relat. Disord. 10, 3-7   DOI   ScienceOn
38 Murphy, G. M., Jr., Yang, L. and Cordell, B. (1998). Macrophage colony-stimulating factor augments beta-amyloid-induced interleukin-1, interleukin-6, and nitric oxide production by microglial cells. J. Biol. Chem. 273, 20967-20971   DOI   ScienceOn
39 Ohkura, Y., Mizoguchi, Y., Morisawa, S., Takeda, S., Aburada, M. and Hosoya, E. (1990). Effect of gomisin A (TJN-101) on the arachidonic acid cascade in macrophages. Jpn. J. Pharmacol. 52, 331-336   DOI
40 Panossian, A. and Wagner, H. (2005). Stimulating effect of adaptogens: an overview with particular reference to their efficacy following single dose administration. Phytother. Res. 19, 819-838   DOI   ScienceOn
41 Segal, R. A. and Greenberg, M. E. (1996). Intracellular signaling pathways activated by neurotrophic factors. Annu. Rev. Neurosci. 19, 463-489   DOI   ScienceOn
42 Pham, C. G., Bubici, C., Zazzeroni, F., Papa, S., Jones, J., Alvarez, K., Jayawardena, S., De Smaele, E., Cong, R., Beaumont, C., Torti, F. M., Torti, S. V. and Franzoso, G. (2004). Ferritin heavy chain upregulation by NF-kappaB inhibits TNFalpha-induced apoptosis by suppressing reactive oxygen species. Cell. 119, 529-542   DOI   ScienceOn
43 Possel, H., Noack, H., Augustin, W., Keilhoff, G. and Wolf, G. (1997). 2,7-Dihydrodichlorofluorescein diacetate as a fluorescent marker for peroxynitrite formation. FEBS. Lett. 416, 175-178   DOI   ScienceOn
44 Salvemini, D., Misko, T. P., Masferrer, J. L., Seibert, K., Currie, M. G. and Needleman, P. (1993). Nitric oxide activates cyclooxygenase enzymes. Proc. Natl. Acad. Sci. U S A. 90, 7240-7244   DOI   ScienceOn
45 Tsai, S. H., Lin-Shiau, S. Y. and Lin, J. K. (1999). Suppression of nitric oxide synthase and the down-regulation of the activation of NFkappaB in macrophages by resveratrol. Br. J. Pharmacol. 126, 673-680   DOI   ScienceOn
46 Xia, Z., Dickens, M., Raingeaud, J., Davis, R. J. and Greenberg, M.E. (1995). Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science. 270, 1326-1331   DOI   ScienceOn
47 Xue, J. Y., Liu, G. T., Wei, H. L. and Pan, Y. (1992). Antioxidant activity of two dibenzocyclooctene lignans on the aged and ischemic brain in rats. Free. Radic. Biol. Med. 12, 127-135   DOI   ScienceOn
48 Yong, V. W., Krekoski, C. A., Forsyth, P. A., Bell, R. and Edwards, D. R. (1998). Matrix metalloproteinases and diseases of the CNS. Trends. Neurosci. 21, 75-80   DOI   ScienceOn
49 Yamada, S., Murawaki, Y. and Kawasaki, H. (1993). Preventive effect of gomisin A, a lignan component of shizandra fruits, on acetaminophen-induced hepatotoxicity in rats. Biochem. Pharmacol. 46, 1081-1085   DOI   ScienceOn
50 Yasukawa, K., Ikeya, Y., Mitsuhashi, H., Iwasaki, M., Aburada, M., Nakagawa, S., Takeuchi, M. and Takido, M. (1992). Gomisin A inhibits tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin. Oncology. 49, 68-71   DOI   ScienceOn
51 Zhang, L. and Niu, X. (1991). Effects of schizandrol A on monoamine neurotransmitters in the central nervous system. Zhongguo. Yi. Xue. Ke. Xue. Yuan. Xue. Bao. 13, 13-16
52 Yu, A. E., Hewitt, R. E., Connor, E. W. and Stetler-Stevenson, W. G. (1997). Matrix metalloproteinases. Novel targets for directed cancer therapy. Drugs. Aging. 11, 229-244   DOI   ScienceOn