대한본초학회지 (The Korea Journal of Herbology)

  • 제28권2호
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  • Pages.93-101
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  • 2013
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  • 1229-1765(pISSN)
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  • 2288-7199(eISSN)
대한본초학회 (The Korea Association of Herbology)
권호 표지
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Baicalein이 Lipopolysaccharide에 의한 생쥐의 Neuroinflammation에 미치는 영향

Effects of Baicalein on Neuroinflammation in Lipopolysaccharide-treated Mice

  • 하경운 (가천대학교 한의과대학 해부경혈학교실) ;
  • 김연섭 (가천대학교 한의과대학 해부경혈학교실)
  • Ha, Gyung-Woon (Department of Anatomy-Pointology, College of Oriental Medicine, Gachon University) ;
  • Kim, Youn-Sub (Department of Anatomy-Pointology, College of Oriental Medicine, Gachon University)
  • 투고 : 2013.02.06
  • 심사 : 2013.03.21
  • 발행 : 2013.03.30
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초록

Objects : Baicalein is a major bioactive flavonoid component of Scutellaria baicalensis Georgi that shows a wide range of biological activities, including neuroprotections and anti-inflammatory actions. Hence it is a potential therapeutic material for the treatment of neuroinflammation. In this study, we investigated the modulatory effect of baicalein on neuroinflammation. Method : Pro-inflammatory cytokines (TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 mRNA), COX-2 mRNA expression and microglial activation in the brain tissue is induced by systemic lipopolysaccharide (LPS) treatment in C57BL/6 mice. Baicalein was treated orally with 10, 20, and 30 mg/kg 1 hour prior to the LPS (3 mg/kg, i.p.) injection. TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and COX-2 mRNA expression in the brain tissue was measured by the quantitative real-time polymerase chain reaction(PCR) method. Iba1 expression in the brain was measured by western blotting method. Microglia was observed with immunohistochemistry. Results : Baicalein 30 mg/kg significantly attenuated the expression of TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and COX-2 mRNA in the brain tissue. Baicalein 20 mg/kg significantly attenuated the expression of IL-6 mRNA in the brain tissue. Baicalein 30 mg/kg significantly attenuated the expression of Iba1 protein expression in the brain tissue. Baicalein 30 mg/kg significantly decreased the number and cell size of microglia in the cerebral cortex and hypothalamic region and the area percentage of Iba1-expressed microglia in the hippocampus. Conclusion : These results demonstrated that baicalein attenuates LPS induced neuroinflammation in the mice via reduction of pro-inflammatory cytokines (TNF-${\alpha}$, IL-$1{\beta}$, IL-6), COX-2 mRNA expression and microglial activation.

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참고문헌

  1. Whitney NP, Eidem TM, Peng H, Huang Y, Zheng JC. Inflammation mediates varying effects in neurogenesis: Relevance to the pathogenesis of brain injury and neurodegenerative disorders. J Neurochem. 2009 ; 108(6) : 1343-59. https://doi.org/10.1111/j.1471-4159.2009.05886.x
  2. Graeber MB, Streit WJ. Microglia: biology and pathology. Acta Neuropathol. 2010 ; 119(1) : 89-105. https://doi.org/10.1007/s00401-009-0622-0
  3. Nagai A, Mishima S, Ishida Y, Ishikura H, Harada T. Immortalized Human Microglial Cell Line: Phenotype Expression. J Neurosci Res. 2005 ; 81 : 342-8. https://doi.org/10.1002/jnr.20478
  4. Kreutzberg GW. Microglia: a sensor for pathological events in the CNS. Trends in Neurosci. 1996 ; 19 : 312-8. https://doi.org/10.1016/0166-2236(96)10049-7
  5. Minghetti, L., Levi, G., Microglia as effector cells in brain damage and repair: focus on prostanoids and nitric oxide. Progress in Neurobil. 1998 ; 54 : 99-125. https://doi.org/10.1016/S0301-0082(97)00052-X
  6. Kang BS, Ko WC, Kim KY, Kim SH, No SH, Park YK, Seo BI, Seo YB, Song SJ, Sin MK, An DK, Lee SI, Lee YJ, Lee KH, Joo YS, Choi HY. Herbal Medicine. Seoul. : Younglimsa 2011 : 217.
  7. Lia HB, Yue J, Feng C. Separation methods used for Scutellaria baicalensis active components. J Chromatogra B. 2004 ; 812 : 277-90. https://doi.org/10.1016/j.jchromb.2004.06.045
  8. Sekiya K, Okuda H. Selective inhibition of platelet lipoxygenase by baicalein. Biochem Biophys Res Cormmun. 1982 ; 105 : 1090-5. https://doi.org/10.1016/0006-291X(82)91081-6
  9. Gao D, Sakurai K, Katoch M, Chen J, Ogiso T. Inhibition of microsomal lipid peroxidation by baicalein : A possible formation of an ironbaicalein complex. Biochem Mol Biol Int. 1996 ; 39 : 215-25.
  10. Yoshino M, Murakami K. Interaction of iron with polyphenolic compounds : application to antioxidation characterization. Anal Biochem. 1998 ; 257 : 40-4. https://doi.org/10.1006/abio.1997.2522
  11. Zhang S, Ye J, Dong G. Neuroprotective effect of baicalein on hydrogen peroxide-mediated oxidative stress and mitochondrial dysfunction in PC12 cells. J Mol Neurosci. 2010 ; 40(3) : 311-20. https://doi.org/10.1007/s12031-009-9285-5
  12. Gao D, Tawa R, Masaki H, Okano Y, Sakurai H. Protective effects of baicalein against cell damage by reactive oxygen species. Chem Pharm Bull. 1998 ; 46 : 1383-7. https://doi.org/10.1248/cpb.46.1383
  13. Lebeau A, Esclaire F, Rostene W, Pelaprat D. Baicalein protects cortical neurons from beta-amloid (25-35) induced toxicity. Neuroreport. 2001; 12(10) : 2199-202. https://doi.org/10.1097/00001756-200107200-00031
  14. Zhang Z, Cui W, Li G, Yuan S, Xu D, Hoi MP, Lin Z, Dou J, Han Y, Lee SM. Baicalein protects against 6-OHDA-induced neurotoxicity through activation of Keap1/Nrf2/HO-1 and involving $PKC{\alpha}$ and PI3K/AKT signaling pathways. J Agric Food Chem. 2012 ;60(33) : 8171-82. https://doi.org/10.1021/jf301511m
  15. Kimura Y, Sumiyoshi M. Effects of baicalein and wogonin isolated from Scutellaria baicalensis roots on skin damage in acute UVB-irradiated hairless mice. Eur J Pharmacol. 2011 ; 661(1-3) : 124-32. https://doi.org/10.1016/j.ejphar.2011.04.033
  16. Li FQ, Wang T, Pei Z, Liu B, Hong JS. Inhibition of microglial activation by the herbal flavonoid baicalein attenuates inflammation-mediated degeneration of dopaminergic neurons. J Neural Transm. 2005 ; 112(3) : 331-47. https://doi.org/10.1007/s00702-004-0213-0
  17. Liu LY, Wei EQ, Zhao YM, Chen FX, Wang ML, Zhang WP, Chen Z. Protective effects of baicalin on oxygen/glucose deprivation- and NMDA-induced injuries in rat hippocampal slices. J Pharm Pharmacol. 2005 ; 57(8) : 1019-26. https://doi.org/10.1211/0022357056622
  18. Cheng Y, He G, Mu X, Zhang T, Li X, Hu J, et al. Neuroprotective effect of baicalein against MPTP neurotoxicity: behavioral, biochemical and immunohistochemical profile. Neurosci Lett. 2008 ; 441(1) : 16-20. https://doi.org/10.1016/j.neulet.2008.05.116
  19. Mu X, He G, Cheng Y, Li X, Xu B, Du G. Baicalein exerts neuroprotective effects in 6 - hydroxydopamine - induced experimental parkin - sonism in vivo and in vitro. Pharmacol Biochem Behav. 2009 ; 92(4) : 642-8. https://doi.org/10.1016/j.pbb.2009.03.008
  20. Jeong K, Shin YC, Park S, Park JS, Kim N, Um JY, Go H, Sun S, Lee S, Park W, Choi Y, Song Y, Kim G, Jeon C, Park J, Lee K, Bang O, Ko SG. Ethanol extract of Scutellaria baicalensis Georgi prevents oxidative damage and neuroinflammation and memorial impairments in artificial senescense mice. J Biomed Sci. 2011 ; 18 : 14. https://doi.org/10.1186/1423-0127-18-14
  21. Zhang G, Ghosh S. Molecular mechanisms of NF-kappaB activation induced by bacterial lipopolysaccharide through Toll-like receptors. J Endotoxin Res. 2000 ; 6(6) : 453-7. https://doi.org/10.1177/09680519000060060701
  22. Konat GW, Kielian T, Marriott I. The role of Toll-like receptors in CNS response to microbial challenge. J Neurochem. 2006 ; 99(1) : 1-12.
  23. Qin L, Wu X, Block ML, Liu Y, Breese GR, Hong JS, Knapp DJ, Crews FT. Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia. 2007 ; 55(5) : 453-62. https://doi.org/10.1002/glia.20467
  24. Evans CH. Nitric oxide: what role does it play in inflamation and tissue destruction?. Agents Actions Suppl. 1995 ; 47 : 107-16.
  25. Huanga Q, Tatroa JB. ${\alpha}$-melanocyte stimulating hormone suppresses intracerebral tumor necrosis factor-a and interleukin-1b gene expression following transient cerebral ischemia in mice. Neuroscience Letters. 2002 ; 334 : 186-90. https://doi.org/10.1016/S0304-3940(02)01088-1
  26. Suo Z, Tan J, Placzek A, Crawford F, Fang C, Mullan M. Alzheimer's ${\beta}$-amyloid peptides induce inflammatory cascade in human vascular cells: the roles of cytokines and CD40. Brain Res. 1998 ; 07(1-2) : 110-7.
  27. Chen SF, Hsu CW, Huang WH, Wang JY. Post-injury baicalein improves histological and functional outcomes and reduces inflammatory cytokines after experimental traumatic brain injury. Br J Pharmacol. 2008 ; 155(8) : 1279-96. https://doi.org/10.1038/bjp.2008.345
  28. Lee GN, Kwon YH : Clinical Pathology File, Seoul : Medical co. 2000 : 169-73.
  29. Lee JS, Cho JY, Song H, Kim EH, Hahm KB. Revaprazan, a novel acid pump antagonist, exerts anti-inflammatory action against Helicobacter pylori-induced COX-2 expression by inactivating Akt signaling. J Clin Biochem Nutr. 2012 ; 51(2) : 77-83. https://doi.org/10.3164/jcbn.11-94
  30. Abraki SB, Khalaj L, Shaerzadeh F, Khodagholi F. Simultaneous Inhibition of COX-2 and Activation of PPAR-${\gamma}$ Resulted in the Same Level and Pattern of Neuroprotection as They were Targeted Separately. J Mol Neurosci. 2013 ; 49(1) : 116-29. https://doi.org/10.1007/s12031-012-9903-5
  31. Chi DS, Lin TC, Hall K, Ha T, Li C, Wu ZD, Soike T, Krishnaswamy G. Enhanced effects of cigarette smoke extract on inflammatory cytokine expression in IL-$1{\beta}$ activated human mast cells were inhibited by Baicalein via regulation of the NF-kB pathway. Clin Mol Allergy. 2012 ; 10 : 3. https://doi.org/10.1186/1476-7961-10-3
  32. Woo KJ, Lim JH, Suh SI, Kwon YK, Shin SW, Kim SC, Choi YH, Park JW, Kwon TK. Differential inhibitory effects of baicalein and baicalin on LPS-induced cyclooxygenase-2 expression through inhibition of C/EBPbeta DNA-binding activity. Immunobiol. 2006 ; 211(5) : 359-68. https://doi.org/10.1016/j.imbio.2006.02.002
  33. Lee EK, Kim JM, Choi J, Jung KJ, Kim DH, Chung SW, Ha YM, Yu BP, Chung HY. Modulation of NF-${\kappa}B$ and FOXOs by baicalein attenuates the radiation-induced inflammatory process in mouse kidney. Free Radic Res. 2011 ; 45(5) : 507-17. https://doi.org/10.3109/10715762.2011.555479
  34. Trang T, Beggs S, Salter MW. ATP receptors gate microglia signaling in neuropathic pain. Exper Neurol. 2012 ; 234 : 354-61. https://doi.org/10.1016/j.expneurol.2011.11.012
  35. Frei K, Malipiero UV, Leist TP, Zinkemagel RM, Schwab ME, Fontana A. On the cellular source and function of interleukin 6 produced in the central nervous system in viral diseases. Eur J Immunol. 1989 ; 19(4) : 689-94. https://doi.org/10.1002/eji.1830190418
  36. Aloisi F, Car'e A, Borsellino G, Gallo P, Rosa S, Bassani A, CabibboA, Testa U, Levi G, Peschle C. Production of hemolymphopoietic cytokines (IL-6, IL-8, colony-stimulating factors) by normal human astrocytes in response to IL-l beta and tumor necrosis factor-alpha. J Immunol. 1992 ; 149(7) : 2358-66.