title: Venenum Bufonis induces rat neuroinflammation by activiating NF-κB pathway and attenuation of BDNF.
abstract: BACKGROUND
  Venenum Bufonis (VB), also called toad venom, has been widely used in clinic as a cardiotonic, anohyne and antineoplastic agents both in China and other Asian countries. However, its neurotoxicity and cardiotoxicity limit its wide clinical application. Compared with extensive attention attracted with cardiotoxicity, the toxic effect of VB on Central Nervous System (CNS) is much less studied.
  
  
  OBJECTIVE
  This study was performed to examine the neurotoxicity caused by VB on Sprague Dawley (SD) rats, then to clarify the mechanism in vivo by investigating its action on the neuroinflammation which possibly attributed to the activation of nuclear factor κB (NF-κB) pathway and the attenuation of brain-derived neurotrophic factor (BDNF).
  
  
  METHODS
  Rats administrated with 0.5% carboxymethyl cellulose sodium salt (CMC-Na) aqueous solution and VB (100mg/kg, 200mg/kg and 400mg/kg) were sacrificed at 2h, 4h, 6h, 8h, 24h and 48h. The brain level of neurotransmitters and their corresponding receptors, pro-inflammatory cytokines, BDNF/TrkB and NF-κB pathway-related proteins were examined, respectively.
  
  
  RESULTS
  VB administration induced severe neurologic damage and neuroinflammation, as indicated by the disordered 5-hydroxytryptamine (5-HT), dopamine (DA) and their corresponding receptors, together with the over production of inflammatory cytokines including interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). VB also notably promoted the expression of p-NF-κBp65, p-IκBα, p-IKKα and p-IKKβ and down-regulated the expression of BDNF and TrkB.
  
  
  CONCLUSIONS
  This study demonstrates that VB triggers neurotoxicity which probably is induced by neuroinflammation via activating of NF-κB pathway and attenuating the expression of BDNF.
authors.affiliation: College of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing 210009, China; Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China. Electronic address: Bqrui2010@126.com.
authors.forename: Qi-Rui
authors.initials: QR
authors.lastname: Bi
authors.affiliation: Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China. Electronic address: houjinjun@hotmail.com.
authors.forename: Jin-Jun
authors.initials: JJ
authors.lastname: Hou
authors.affiliation: Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China. Electronic address: pengqsmart@live.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Qi
authors.affiliation: College of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing 210009, China. Electronic address: machunhua25@126.com.
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Ma
authors.affiliation: Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China. Electronic address: yao.shen2010@outlook.com.
authors.forename: Yao
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China. Electronic address: rita1225@126.com.
authors.forename: Rui-Hong
authors.initials: RH
authors.lastname: Feng
authors.affiliation: College of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing 210009, China; Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China. Electronic address: Semo519@163.com.
authors.forename: Bing-Peng
authors.initials: BP
authors.lastname: Yan
authors.affiliation: College of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing 210009, China; Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China. Electronic address: wwwjw@hotmail.com.
authors.forename: Jian-Wei
authors.initials: JW
authors.lastname: Wang
authors.affiliation: College of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing 210009, China; Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China. Electronic address: sxjianjnu@163.com.
authors.forename: Xiao-Jian
authors.initials: XJ
authors.lastname: Shi
authors.affiliation: Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China. Electronic address: 1432165613@qq.com.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Zheng
authors.affiliation: Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China. Electronic address: wanyingwu@simm.ac.cn.
authors.forename: Wan-Ying
authors.initials: WY
authors.lastname: Wu
authors.affiliation: College of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing 210009, China; Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China. Electronic address: daguo@simm.ac.cn.
authors.forename: Dean
authors.initials: D
authors.lastname: Guo
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002018:Bufanolides / Q000633:toxicity*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D007249:Inflammation / Q000139:chemically induced*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002018:Bufanolides; D016207:Cytokines; D016328:NF-kappa B; C095591:chan su
keywords: Arenobufagin (PubChem CID: 12305198); Brain-derived neurotrophic factor (BDNF); Bufalin (PubChem CID: 9547215); Bufotalin (PubChem CID: 259578); Cinobufagin (PubChem CID: 11969541); Cinobufotalin (PubChem CID: 259776); Desacetylbufotalin (PubChem CID: 12358889); Hellebrigenin (PubChem CID: 259577); Inflammation; NF-<kappa>B pathway; Neurotoxicity; Resibufogenin (PubChem CID: 6917974); Telocinobufagin (PubChem CID: 259991); Venenum Bufonis