DOI QR코드

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α-Asarone Ameliorates Memory Deficit in Lipopolysaccharide-Treated Mice via Suppression of Pro-Inflammatory Cytokines and Microglial Activation

  • Shin, Jung-Won (Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Cheong, Young-Jin (Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Koo, Yong-Mo (Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Kim, Sooyong (Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Noh, Chung-Ku (Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Son, Young-Ha (Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Kang, Chulhun (Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Sohn, Nak-Won (Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University)
  • 투고 : 2013.11.26
  • 심사 : 2014.01.10
  • 발행 : 2014.01.31

초록

${\alpha}$-Asarone exhibits a number of pharmacological actions including neuroprotective, anti-oxidative, anticonvulsive, and cognitive enhancing action. The present study investigated the effects of ${\alpha}$-asarone on pro-inflammatory cytokines mRNA, microglial activation, and neuronal damage in the hippocampus and on learning and memory deficits in systemic lipopolysaccharide (LPS)-treated C57BL/6 mice. Varying doses of ${\alpha}$-asarone was orally administered (7.5, 15, or 30 mg/kg) once a day for 3 days before the LPS (3 mg/kg) injection. ${\alpha}$-Asarone significantly reduced TNF-${\alpha}$ and IL-$1{\beta}$ mRNA at 4 and 24 hours after the LPS injection at dose of 30 mg/kg. At 24 hours after the LPS injection, the loss of CA1 neurons, the increase of TUNEL-labeled cells, and the up-regulation of BACE1 expression in the hippocampus were attenuated by 30 mg/kg of ${\alpha}$-asarone treatment. ${\alpha}$-Asarone significantly reduced Iba1 protein expression in the hippocampal tissue at a dose of 30 mg/kg. ${\alpha}$-Asarone did not reduce the number of Iba1-expressing microglia on immunohistochemistry but the average cell size and percentage areas of Iba1-expressing microglia in the hippocampus were significantly decreased by 30 mg/kg of ${\alpha}$-asarone treatment. In the Morris water maze test, ${\alpha}$-asarone significantly prolonged the swimming time spent in the target and peri-target zones. ${\alpha}$-Asarone also significantly increased the number of target heading and memory score in the Morris water maze. The results suggest that inhibition of pro-inflammatory cytokines and microglial activation in the hippocampus by ${\alpha}$-asarone may be one of the mechanisms for the ${\alpha}$-asarone-mediated ameliorating effect on memory deficits.

키워드

참고문헌

  1. Alvarez, A., Cacabelos, R., Sanpedro, C., Garcia-Fantini, M. and Aleixandre, M. (2007) Serum TNF-alpha levels are increased and correlate negatively with free IGF-I in Alzheimer disease. Neurobiol. Aging 28, 533-536. https://doi.org/10.1016/j.neurobiolaging.2006.02.012
  2. Baier, P. C., May, U., Scheller, J., Rose-John, S. and Schiffelholz, T. (2009) Impaired hippocampus-dependent and -independent learning in IL-6 deficient mice. Behav. Brain Res. 200, 192-196. https://doi.org/10.1016/j.bbr.2009.01.013
  3. Belarbi, K., Jopson, T., Tweedie, D., Arellano, C., Luo, W., Greig, N. H. and Rosi, S. (2012) TNF-alpha protein synthesis inhibitor restores neuronal function and reverses cognitive deficits induced by chronic neuroinflammation. J. Neuroinflammation 9, 23. https://doi.org/10.1186/1742-2094-9-23
  4. Blasko, I., Marx, F., Steiner, E., Hartmann, T. and Grubeck-Loebenstein, B. (1999) TNFalpha plus IFNgamma induce the production of Alzheimer beta-amyloid peptides and decrease the secretion of APPs. FASEB J. 13, 63-68. https://doi.org/10.1096/fasebj.13.1.63
  5. Block, M. L., Zecca, L. and Hong, J. S. (2007) Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat. Rev. Neurosci. 8, 57-69. https://doi.org/10.1038/nrn2038
  6. Buxbaum, J. D., Oishi, M., Chen, H. I., Pinkas-Kramarski, R., Jaffe, E. A., Gandy, S. E. and Greengard, P. (1992) Cholinergic agonists and interleukin 1 regulate processing and secretion of the Alzheimer beta/A4 amyloid protein precursor. Proc. Natl. Acad. Sci. U.S.A. 89, 10075-10078. https://doi.org/10.1073/pnas.89.21.10075
  7. Chen, Q. X., Miao, J. K., Li, C., Li, X. W., Wu, X. M. and Zhang, X. P. (2013) Anticonvulsant activity of acute and chronic treatment with a-asarone from Acorus gramineus in seizure models. Biol. Pharm. Bull. 36, 23-30.
  8. Cho, J., Kim, Y. H., Kong, J. Y., Yang, C. H. and Park, C. G. (2002) Protection of cultured rat cortical neurons from excitotoxicity by asarone, a major essential oil component in the rhizomes of Acorus gramineus. Life Sci. 71, 591-599. https://doi.org/10.1016/S0024-3205(02)01729-0
  9. Choi, M., Kwak, H., Kweon, K., Hwang, J., Shin, J. and Sohn, N. (2013) Effects of ${\beta}$-asarone on pro-inflammatory cytokines and learning and memory impairment in lipopolysaccharide-treated mice. Kor. J. Herbology 28, 119-127. https://doi.org/10.6116/kjh.2013.28.6.119
  10. Gallagher, J. J., Minogue, A. M. and Lynch, M. A. (2013) Impaired performance of female APP/PS1 mice in the Morris water maze is coupled with increased Abeta accumulation and microglial activation. Neurodegener. Dis. 11, 33-41. https://doi.org/10.1159/000337458
  11. Geng, Y., Li, C., Liu, J., Xing, G., Zhou, L., Dong, M., Li, X. and Niu, Y. (2010) Beta-asarone improves cognitive function by suppressing neuronal apoptosis in the beta-amyloid hippocampus injection rats. Biol. Pharm. Bull. 33, 836-843. https://doi.org/10.1248/bpb.33.836
  12. Graeber, M. B. and Streit, W. J. (2010) Microglia: biology and pathology. Acta Neuropathol. 119, 89-105. https://doi.org/10.1007/s00401-009-0622-0
  13. Griffin, R., Nally, R., Nolan, Y., McCartney, Y., Linden, J. and Lynch, M. A. (2006) The age-related attenuation in long-term potentiation is associated with microglial activation. J. Neurochem. 99, 1263-1272. https://doi.org/10.1111/j.1471-4159.2006.04165.x
  14. Han, P., Han, T., Peng, W. and Wang, X. R. (2013) Antidepressant-like effects of essential oil and asarone, a major essential oil component from the rhizome of Acorus tatarinowii. Pharm. Biol. 51, 589-594. https://doi.org/10.3109/13880209.2012.751616
  15. Harry, G. J. and Kraft, A. D. (2008) Neuroinflammation and microglia: considerations and approaches for neurotoxicity assessment. Expert Opin. Drug Metab. Toxicol. 4, 1265-1277. https://doi.org/10.1517/17425255.4.10.1265
  16. Hein, A. M., Stutzman, D. L., Bland, S. T., Barrientos, R. M., Watkins, L. R., Rudy, J. W. and Maier, S. F. (2007) Prostaglandins are necessary and sufficient to induce contextual fear learning impairments after interleukin-1 beta injections into the dorsal hippocampus. Neuroscience 150, 754-763. https://doi.org/10.1016/j.neuroscience.2007.10.003
  17. Heneka, M. T., Sastre, M., Dumitrescu-Ozimek, L., Dewachter, I., Walter, J., Klockgether, T. and Van Leuven, F. (2005) Focal glial activation coincides with increased BACE1 activation and precedes amyloid plaque deposition in APP[V717I] transgenic mice. J. Neuroinflammation 2, 22. https://doi.org/10.1186/1742-2094-2-22
  18. Huang, C., Li, W. G., Zhang, X. B., Wang, L., Xu, T. L., Wu, D. and Li, Y. (2013) ${\alpha}$-asarone from Acorus gramineus alleviates epilepsy by modulating A-type GABA receptors. Neuropharmacology 65, 1-11. https://doi.org/10.1016/j.neuropharm.2012.09.001
  19. Imamura, Y., Wang, H., Matsumoto, N., Muroya, T., Shimazaki, J., Ogura, H. and Shimazu, T. (2011) Interleukin-1beta causes long-term potentiation deficiency in a mouse model of septic encephalopathy. Neuroscience 187, 63-69. https://doi.org/10.1016/j.neuroscience.2011.04.063
  20. Jeong, H. K., Jou, I. and Joe, E. H. (2010) Systemic LPS administration induces brain inflammation but not dopaminergic neuronal death in the substantia nigra. Exp. Mol. Med. 42, 823-832. https://doi.org/10.3858/emm.2010.42.12.085
  21. Kim, J. H., Hahm, D. H., Lee, H. J., Pyun, K. H. and Shim, I. (2009) Acori graminei rhizoma ameliorated ibotenic acid-induced amnesia in rats. Evid. Based Complement. Alternat. Med. 6, 457-464. https://doi.org/10.1093/ecam/nem158
  22. Kumar, H., Kim, B. W., Song, S. Y., Kim, J. S., Kim, I. S., Kwon, Y. S., Koppula, S. and Choi, D. K. (2012) Cognitive enhancing effects of alpha asarone in amnesic mice by influencing cholinergic and antioxidant defense mechanisms. Biosci. Biotechnol. Biochem. 76, 1518-1522. https://doi.org/10.1271/bbb.120247
  23. Lee, J. W., Lee, Y. K., Yuk, D. Y., Choi, D. Y., Ban, S. B., Oh, K. W. and Hong, J. T. (2008) Neuro-inflammation induced by lipopolysaccharide causes cognitive impairment through enhancement of beta-amyloid generation. J. Neuroinflammation 5, 37. https://doi.org/10.1186/1742-2094-5-37
  24. Li, C., Xing, G., Dong, M., Zhou, L., Li, J., Wang, G., Zou, D., Wang, R., Liu, J. and Niu, Y. (2010) Beta-asarone protection against beta-amyloid-induced neurotoxicity in PC12 cells via JNK signaling and modulation of Bcl-2 family proteins. Eur. J. Pharmacol. 635, 96-102. https://doi.org/10.1016/j.ejphar.2010.03.013
  25. Li, Z., Zhao, G., Qian, S., Yang, Z., Chen, X., Chen, J., Cai, C., Liang, X. and Guo, J. (2012) Cerebrovascular protection of beta-asarone in Alzheimer's disease rats: a behavioral, cerebral blood flow, biochemical and genic study. J. Ethnopharmacol. 144, 305-312. https://doi.org/10.1016/j.jep.2012.09.013
  26. Lien, E., Means, T. K., Heine, H., Yoshimura, A., Kusumoto, S., Fukase, K., Fenton, M. J., Oikawa, M., Qureshi, N., Monks, B., Finberg, R. W., Ingalls, R. R. and Golenbock, D. T. (2000) Toll-like receptor 4 imparts ligand-specific recognition of bacterial lipopolysaccharide. J. Clin. Invest. 105, 497-504. https://doi.org/10.1172/JCI8541
  27. Limon, I. D., Mendieta, L., Diaz, A., Chamorro, G., Espinosa, B., Zenteno, E. and Guevara, J. (2009) Neuroprotective effect of alpha-asarone on spatial memory and nitric oxide levels in rats injected with amyloid-beta(25-35). Neurosci. Lett. 453, 98-103. https://doi.org/10.1016/j.neulet.2009.02.011
  28. Liu, M. C., Liu, X. Q., Wang, W., Shen, X. F., Che, H. L., Guo, Y. Y., Zhao, M. G., Chen, J. Y. and Luo, W. J. (2012a) Involvement of microglia activation in the lead induced long-term potentiation impairment. PLoS One 7, e43924. https://doi.org/10.1371/journal.pone.0043924
  29. Liu, S., Chen, S. W., Xu, N., Liu, X. H., Zhang, H., Wang, Y. Z. and Xu, X. D. (2012b). Anxiolytic-like effect of alpha-asarone in mice. Phytother. Res. 26, 1476-1481.
  30. Liu, X., Wu, Z., Hayashi, Y. and Nakanishi, H. (2012c) Age-dependent neuroinflammatory responses and deficits in long-term potentiation in the hippocampus during systemic inflammation. Neuroscience 216, 133-142. https://doi.org/10.1016/j.neuroscience.2012.04.050
  31. Manikandan, S. and Devi, R. S. (2005) Antioxidant property of alpha-asarone against noise-stress-induced changes in different regions of rat brain. Pharmacol. Res. 52, 467-474. https://doi.org/10.1016/j.phrs.2005.07.007
  32. Mishra, A., Kim, H. J., Shin, A. H. and Thayer, S. A. (2012) Synapse loss induced by interleukin-1beta requires pre- and post-synaptic mechanisms. J. Neuroimmune Pharmacol. 7, 571-578. https://doi.org/10.1007/s11481-012-9342-7
  33. Pages, N., Maurois, P., Delplanque, B., Bac, P., Stables, J. P., Tamariz, J., Chamorro, G. and Vamecq, J. (2010) Activities of alpha-asarone in various animal seizure models and in biochemical assays might be essentially accounted for by antioxidant properties. Neurosci. Res. 68, 337-344. https://doi.org/10.1016/j.neures.2010.08.011
  34. Park, S. M., Choi, M. S., Sohn, N. W. and Shin, J. W. (2012) Ginsenoside Rg3 attenuates microglia activation following systemic lipopolysaccharide treatment in mice. Biol. Pharm. Bull. 35, 1546-1552. https://doi.org/10.1248/bpb.b12-00393
  35. Sastre, M., Dewachter, I., Landreth, G. E., Willson, T. M., Klockgether, T., van Leuven, F. and Heneka, M. T. (2003) Nonsteroidal anti-inflammatory drugs and peroxisome proliferator-activated receptor-gamma agonists modulate immunostimulated processing of amyloid precursor protein through regulation of beta-secretase. J. Neurosci. 23, 9796-9804.
  36. Sastre, M., Walter, J. and Gentleman, S. M. (2008) Interactions between APP secretases and inflammatory mediators. J. Neuroinflammation 5, 25. https://doi.org/10.1186/1742-2094-5-25
  37. Shaw, K. N., Commins, S. and O'Mara, S. M. (2001) Lipopolysaccharide causes deficits in spatial learning in the watermaze but not in BDNF expression in the rat dentate gyrus. Behav. Brain Res. 124, 47-54. https://doi.org/10.1016/S0166-4328(01)00232-7
  38. Smith, D. H., Okiyama, K., Thomas, M. J. and McIntosh, T. K. (1993) Effects of the excitatory amino acid receptor antagonists kynurenate and indole-2-carboxylic acid on behavioral and neurochemical outcome following experimental brain injury. J. Neurosci. 13, 5383-5392.
  39. Thomson, L. M. and Sutherland, R. J. (2005) Systemic administration of lipopolysaccharide and interleukin-1beta have different effects on memory consolidation. Brain Res. Bull. 67, 24-29. https://doi.org/10.1016/j.brainresbull.2005.05.024
  40. Wei, G., Chen, Y. B., Chen, D. F., Lai, X. P., Liu, D. H., Deng, R. D., Zhou, J. H., Zhang, S. X., Li, Y. W., Lii, H., Liu, L. F., Wang, Q. and Nie, H. (2013) beta-Asarone inhibits neuronal apoptosis via the CaMKII/CREB/Bcl-2 signaling pathway in an in vitro model and AbetaPP/PS1 mice. J. Alzheimers Dis. 33, 863-880.
  41. Wu, M. D., Montgomery, S. L., Rivera-Escalera, F., Olschowka, J. A. and O'Banion, M. K. (2013) Sustained IL-1beta expression impairs adult hippocampal neurogenesis independent of IL-1 signaling in nestin+ neural precursor cells. Brain Behav. Immun. 32, 9-18. https://doi.org/10.1016/j.bbi.2013.03.003
  42. Zhang, H., Han, T., Yu, C. H., Rahman, K., Qin, L. P. and Peng, C. (2007) Ameliorating effects of essential oil from Acori graminei rhizoma on learning and memory in aged rats and mice. J. Pharm. Pharmacol. 59, 301-309. https://doi.org/10.1211/jpp.59.2.0016
  43. Zou, D. J., Wang, G., Liu, J. C., Dong, M. X., Li, X. M., Zhang, C., Zhou, L., Wang, R. and Niu, Y. C. (2011) Beta-asarone attenuates beta-amyloid-induced apoptosis through the inhibition of the activation of apoptosis signal-regulating kinase 1 in SH-SY5Y cells. Pharmazie 66, 44-51.

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