期刊论文详细信息
BMC Complementary and Alternative Medicine
The effect of Lycium barbarum on spinal cord injury, particularly its relationship with M1 and M2 macrophage in rats
Gong Ju3  Kwok-Fai So1  Raymond Chuen-Chung Chang2  Ling Liu3  Jian Wang3  Yu-Kai Zhang3 
[1] Faculty of Medicine, The University of Hong Kong, 1/F Laboratory Block, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China;State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China;Institute of Neurosciences, Fourth Military Medical University, Chang Le Xi Road, Xi’an, Shan Xi, 710032, China
关键词: Rat;    Macrophage;    Spinal cord injury;    L. barbarum;   
Others  :  1230145
DOI  :  10.1186/1472-6882-13-67
 received in 2012-08-07, accepted in 2013-02-25,  发布年份 2013
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【 摘 要 】

Background

Our past researches suggested that L. barbarum exhibits direct neuroprotective and immune regulatory effects on the central nervous system, which are highly related to the events involved in the spinal cord injury, but not yet been investigated. Immune responses play an important role in the development of the pathology after secondary injury, particularly the M1 and M2 types of macrophage, on which special emphasis was laid in this study.

Methods

In our previous studies L. barbarum was administrated orally from 7 days before the injury to ensure a stabilized concentration in the blood. For clinical application, L. barbarum can only be administered after the injury. Therefore, both pre-injury and post-injury administration protocols were compared. In vivo and in vitro studies were conducted and analyzed immunohistochemically, including Western blotting.

Results

The lesion size in the pre-treated group was much larger than that in the post-treated group. To explain this difference, we first studied the effect of L. barbarum on astrocytes, which forms the glial scar encircling the lesion. L. barbarum did not significantly affect the astrocytes. Then we studied the effect of L. barbarum on microglia/macrophages, particularly the M1 and M2 polarization. After spinal cord injury, the deleterious M1 cells dominant the early period, whereas the beneficial M2 cells dominate later. We found that in the pre-treated group L. barbarum significantly enhanced the expression of M1 cells and suppressed that of M2 cells, while in the post-treated group LBP markedly promoted the activity of M2 cells. This explained the difference between the pre- and post-treated groups.

Conclusions

Lycium barbarum has been wildly accepted to have beneficial effects in various central nervous system diseases. Our finding of deleterious effect of LBP administered at early period of spinal cord injury, indicates that its application should be avoided. The substantial beneficial effect of LBP when administered at later stage has an important impact for clinical application.

【 授权许可】

   
2013 Zhang et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Kalb RG, Strimatter SM: Neurobiology of Spinal Cord Injury. Totowa, New Jersey: Humana Press; 2000.
  • [2]Kordower JH, Tuszynski MH: Basic science and Clinical Advances. New York: Academic; 2008.
  • [3]Zhu H, Feng YP, Young W, You SW, Shen XF, Liu YS, Ju G: Early neurosurgical intervention of spinal cord contusion: an analysis of 30 cases. Chin Med J (Engl) 2008, 121:2473-2478.
  • [4]Trivedi A, Olivas AD, Noble-Haeusslein LJ: Inflammation and spinal cord injury: infiltrating leukocytes as determinants of injury and repair processes. Clin Neurosci Res 2006, 6:283-292.
  • [5]David S, Kroner A: Repertoire of microglial and macrophage responses after spinal cord injury. Nat Rev Neurosci 2011, 12:388-399.
  • [6]Walter L, Neumann H: Role of microglia in neuronal degeneration and regeneration. Semin Immunopathol 2009, 31:513-525.
  • [7]Loane DJ, Byrnes KR: Role of microglia in neurotrauma. Neurotherapeutics 2010, 7:366-377.
  • [8]Kigerl KA, Gensel JC, Ankeny DP, Alexander JK, Donnelly DJ, Popovich PG: Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J Neurosci 2009, 29:13435-13444.
  • [9]Ho YS, So KF, Chang RC: Anti-aging herbal medicine–how and why can they be used in aging-associated neurodegenerative diseases? Ageing Res Rev 2010, 9:354-362.
  • [10]Chang RC, So KF: Use of anti-aging herbal medicine, Lycium barbarum, against aging-associated diseases. What do we know so far? Cell Mol Neurobiol 2008, 28:643-652.
  • [11]Yu MS, Lai CS, Ho YS, Zee SY, So KF, Yuen WH, Chang RC: Characterization of the effects of anti-aging medicine Fructus lycii on beta-amyloid peptide neurotoxicity. Int J Mol Med 2007, 20:261-268.
  • [12]Ho YS, Yu MS, Lai CS, So KF, Yuen WH, Chang RC: Characterizing the neuroprotective effects of alkaline extract of Lycium barbarum on beta-amyloid peptide neurotoxicity. Brain Res 2007, 1158:123-134.
  • [13]Yu MS, Ho YS, So KF, Yuen WH, Chang RC: Cytoprotective effects of Lycium barbarum against reducing stress on endoplasmic reticulum. Int J Mol Med 2006, 17:1157-1161.
  • [14]Huang X, Yang M, Wu X, Yan J: Study on protective action of lycium barbarum polysaccharides on DNA imparments of testicle cells in mice. Wei Sheng Yan Jiu 2003, 32:599-601.
  • [15]Ho YS, Yu MS, Yik SY SOKF, Yuen WH, Chang RC: Polysaccharides from wolfberry antagonizes glutamate excitotoxicity in rat cortical neurons. Cell Mol Neurobiol 2009, 29:1233-1244.
  • [16]Chiu K, Chan HC, Yeung SC, Yuen WH, Zee SY, Chang RC, SO KF: Modulation of microglia by Wolfberry on the survival of retinal ganglion cells in a rat ocular hypertension model. J Ocul Biol Dis Infor 2009, 2:47-56.
  • [17]Chan HC, Chang RC, Koon-Ching IA, Chiu K, Yuen WH, Zee SY, SO KF: Neuroprotective effects of Lycium barbarum Lynn on protecting retinal ganglion cells in an ocular hypertension model of glaucoma. Exp Neurol 2007, 203:269-273.
  • [18]Chiu K, Zhou Y, Yeung SC, Lok CK, Chan OO, Chang RC, SO KF, Chiu JF: Up-regulation of crystallins is involved in the neuroprotective effect of wolfberry on survival of retinal ganglion cells in rat ocular hypertension model. J Cell Biochem 2010, 110:311-320.
  • [19]Gan L, Zhang SH, Liu Q, Xu HB: A polysaccharide-protein complex from Lycium barbarum upregulates cytokine expression in human peripheral blood mononuclear cells. Eur J Pharmacol 2003, 471:217-222.
  • [20]Gan L, Hua ZS, Liang YX, Bi XH: Immunomodulation and antitumor activity by a polysaccharide-protein complex from Lycium barbarum. Int Immunopharmacol 2004, 4:563-569.
  • [21]Zhu J, Zhao LH, Zhao XP, Chen Z: Lycium barbarum polysaccharides regulate phenotypic and functional maturation of murine dendritic cells. Cell Biol Int 2007, 31:615-619.
  • [22]Li XM, Ma YL, Liu XJ: Effect of the Lycium barbarum polysaccharides on age-related oxidative stress in aged mice. J Ethnopharmacol 2007, 111:504-511.
  • [23]Niu AJ, Wu JM, Yu DH, Wang R: Protective effect of Lycium barbarum polysaccharides on oxidative damage in skeletal muscle of exhaustive exercise rats. Int J Biol Macromol 2008, 42:447-449.
  • [24]Tulsky JA: Ancient wisdom for modern medicine. The tradition of Judaism. N C Med J 2000, 61:141-144.
  • [25]Li XM: Protective effect of Lycium barbarum polysaccharides on streptozotocin-induced oxidative stress in rats. Int J Biol Macromol 2007, 40:461-465.
  • [26]Xin YF, Wan LL, Peng JL, Guo C: Alleviation of the acute doxorubicin-induced cardiotoxicity by Lycium barbarum polysaccharides through the suppression of oxidative stress. Food Chem Toxicol 2011, 49:259-264.
  • [27]Bodrato N, Franco L, Fresia C, Guida L, Usai C, Salis A, Moreschi I, Ferraris C, Verderio C, Basile G: Abscisic acid activates the murine microglial cell line N9 through the second messenger cyclic ADP-ribose. J Biol Chem 2009, 284:14777-14787.
  • [28]Lu X, Ma L, Ruan L, Kong Y, Mou H, Zhang Z, Wang Z, Wang JM, Le Y: Resveratrol differentially modulates inflammatory responses of microglia and astrocytes. J Neuroinflammation 2010, 7:46. BioMed Central Full Text
  • [29]Wu VW, Nishiyama N, Schwartz JP: A culture model of reactive astrocytes: increased nerve growth factor synthesis and reexpression of cytokine responsiveness. J Neurochem 1998, 71:749-756.
  • [30]Sofroniew MV: Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci 2009, 32:638-647.
  • [31]Voskuhl RR, Peterson RS, Song B, Ao Y, Morales LB, Tiwari-Woodruff S, Sofroniew MV: Reactive astrocytes form scar-like perivascular barriers to leukocytes during adaptive immune inflammation of the CNS. J Neurosci 2009, 29:11511-11522.
  • [32]Bechmann I, Lossau S, Steiner B, Mor G, Gimsa U, Nitsch R: Reactive astrocytes upregulate Fas (CD95) and Fas ligand (CD95L) expression but do not undergo programmed cell death during the course of anterograde degeneration. Glia 2000, 32:25-41.
  • [33]Corradin SB, Mauel J, Donini SD, Quattrocchi E, Ricciardi-Castagnoli P: Inducible nitric oxide synthase activity of cloned murine microglial cells. Glia 1993, 7:255-262.
  • [34]Roitbak T, Sykova E: Diffusion barriers evoked in the rat cortex by reactive astrogliosis. Glia 1999, 28:40-48.
  • [35]Plemel JR, Duncan G, Chen KW, Shannon C, Park S, Sparling JS, Tetzlaff W: A graded forceps crush spinal cord injury model in mice. J Neurotrauma 2008, 25:350-370.
  • [36]Eng LF, Ghirnikar RS: GFAP and astrogliosis. Brain Pathol 1994, 4:229-237.
  • [37]Rolls A, Shechter R, Schwartz M: The bright side of the glial scar in CNS repair. Nat Rev Neurosci 2009, 10:235-241.
  • [38]Reier PJ, Houle JD: The glial scar: its bearing on axonal elongation and transplantation approaches to CNS repair. Adv Neurol 1988, 47:87-138.
  • [39]Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M: The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 2004, 25:677-686.
  • [40]Martinez FO, Sica A, Mantovani A, Locati M: Macrophage activation and polarization. Front Biosci 2008, 13:453-461.
  • [41]Chan CC: Inflammation: beneficial or detrimental after spinal cord injury? Recent Pat CNS Drug Discov 2008, 3:189-199.
  • [42]Gensel JC, Nakamura S, Guan Z, van Rooijen N, Ankeny DP, Popovich PG: Macrophages promote axon regeneration with concurrent neurotoxicity. J Neurosci 2009, 29:3956-3968.
  • [43]Murray PJ, Wynn TA: Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol 2011, 11:723-737.
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