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Role of baicalin in regulating Toll-like receptor 2/4 after ischemic neuronal injury

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Author:: No author available

Journal Title:: Chinese Medical Journal

Issue:: 9

DOI:: 10.3760/cma.j.issn.0366-6999.2012.09.012

Key Word:: Toll-like receptor 2/4;baicalin;neuron;oxygen glucose deprivation;cerebral ischemia-reperfusion

Abstract： Background Baicalin has a significant anti-inflammation effect and is widely used in the clinical treatment of stroke.Most of the studies of Toll-like receptor 2/4 (TLR2/4) during cerebral ischemia had defined their specific expressions in microglia in hippocampus tissue.To explore the targets of baicalin in stroke,we detected the expressions of TLR2/4 in vitrolvivo.Methods By constructing a cerebral ischemia-reperfusion model in vivo and glucose oxygen deprivation model,we successfully induced neuron damage,then added baicalin and detected expressions of TLR2/4,nuclear factor-κB (NF-κB),tumor necrosis factor-alpha (TNFa),and interleukin-1β (IL-1β)in mRNA level and protein level.Results We found distinct upregulations of TLR2/4 and TNFα in both mRNA level and protein level in PC12 cells and primary neurons.Moreover,TLR2/4 and TNFα expressions were significantly higher in mice hippocampus treated with cerebral ischemia-reperfusion.Baicalin could downregulate the expressions of TLR2/4 and TNFα in the damaged cells and mice hippocampus effectively.Conclusions Neurons could respond to the damage and activate the related signal pathway directly.TLR2/4responsed to the damage and sent the signal to downstream factor TNFα through activating NF-κB.Baicalin could inhibit the inflammatory reaction in neuron damage and TLR might be its targets,which explained why baicalin could widely be used in the clinical treatment of stroke.

Reference

[1]邢东明,国月英,炎彬,等.缺血再灌卒中后抑郁小鼠模型的建立[J].2009,(3).
[2]ZHAO Yu'nan,SHEN Jia,SU Hui,etc.Long-Term Exposure to High Corticosterone Levels Inducing a Decrease of Adenylate Kinase 1 Activity[J].2009,(4).
[3]Doyle SL,O'Neill LA.Toll-like receptors: from the discovery of NFkappaB to new insights into transcriptional regulations in innate immunity.[J].2006,72(9).
[4]S, Nagahiro,M, Uno,K, Sato,etc.Pathophysiology and treatment of cerebral ischemia.[J].1998,45.
[5]R, Medzhitov.Toll-like receptors and innate immunity.[J].2001,1(2).
[6]Alleva LM,Vissel B,Clark IA.The roles of TNF in brain dysfunction and disease.[J].2010,128(3).
[7]Prinjha RK,Soden PE,Burbidge SA,etc.Abeta(1-42) reduces synapse number and inhibits neurite outgrowth in primary cortical and hippocampal neurons: a quantitative analysis.[J].2008,175(1).
[8]Sun ZH,Li P,Zhang WS,etc.A comparative study on the individual and combined effects of baicalin and jasminoidin on focal cerebral ischemia-reperfusion injury.[J].2006,1123(1).
[9]Chang S,Mazumdar K,Seong SY,etc.TLR4-independent and PKR-dependent interleukin 1 receptor antagonist expression upon LPS stimulation.[J].2009,259(1).
[10]Marco A, Campos,Ricardo T, Gazzinelli.Trypanosoma cruzi and its components as exogenous mediators of inflammation recognized through Toll-like receptors.[J].2004,13(3).
[11]Li H,Li Y,Zhang.Toll-like receptor 2 is required for opioids-induced neuronal apoptosis.[J].2010,391(1).
[12]杜力军,於兰.小鼠不完全性脑缺血、再灌注时脑膜血流量的变化及尼莫地平的作用[J].1997,(3).
[13]Cheng A,Son TG,Lee JH,etc.TLR2 activation inhibits embryonic neural progenitor cell proliferation.[J].2010,114(2).
[14]Lixuan Z,Jingcheng D,Xiaotao F,etc.Baicalin attenuates inflammation by inhibiting NF-kappaB activation in cigarette smoke induced inflammatory models.[J].2010,23(5).
[15]Hailer NP.Immunosuppression after traumatic or ischemic CNS damage: it is neuroprotective and illuminates the role of microglial cells.[J].2008,84(3).
[16]Selvaraj PK,Markesbery WR,Mattson MP,etc.Toll-like receptor-4 mediates neuronal apoptosis induced by amyloid beta-peptide and the membrane lipid peroxidation product 4-hydroxynonenal.[J].2008,213(1).
[17]Ha T,Ma J,Hua F.Differential roles of TLR2 and TLR4 in acute focal cerebral ischemia/reperfusion injury in mice.[J].2009,1262.
[18]Perry VH,Teeling JL.Systemic infection and inflammation in acute CNS injury and chronic neurodegeneration: underlying mechanisms.[J].2009,158(3).
[19]Fang X,Tong Y,Gao Y.TLR4-mediated MyD88-dependent signaling pathway is activated by cerebral ischemia-reperfusion in cortex in mice.[J].2009,63(6).
[20]Kung H,Dunlop N,Li BQ,etc.The flavonoid baicalin exhibits anti-inflammatory activity by binding to chemokines.[J].2000,49(3).
[21]Napoli I,Neumann H.Microglial clearance function in health and disease.[J].2009,158(3).
[22]Schwaninger M,Ridder DA.NF-kappaB signaling in cerebral ischemia.[J].2009,158(3).
[23]Copanaki E,Deller T,Burbach GJ,etc.Differential regulation of toll-like receptor mRNAs in amyloid plaque-associated brain tissue of aged APP23 transgenic mice.[J].2009,453(1).
[24]Ock J,Kim S,Yi K.A novel anti-neuroinflammatory pyridylimidazole compound KR-31360.[J].2010,79(4).
[25]Xing D,Wang R,Wang W,etc.Kinetic difference of baicalin in rat blood and cerebral nuclei after intravenous administration of Scutellariae Radix extract.[J].2006,103(1).
[26]Wang X,Hu J,Lei F,etc.Comprehensive study of baicalin down-regulating NOD2 receptor expression of neurons with oxygen-glucose deprivation in vitro and cerebral ischemia-reperfusion in vivo.[J].2010,649(1).