title: Sinomenine protects against ischaemic brain injury: involvement of co-inhibition of acid-sensing ion channel 1a and L-type calcium channels.
abstract: OBJECTIVE
  Sinomenine (SN), a bioactive alkaloid, has been utilized clinically to treat rheumatoid arthritis in China. Our preliminary experiments indicated that it could protect PC12 cells from oxygen-glucose deprivation-reperfusion (OGD-R), we thus investigated the possible effects of SN on cerebral ischaemia and the related mechanism.
  
  
  METHODS
  Middle cerebral artery occlusion in rats was used as an animal model of ischaemic stroke in vivo. The mechanisms of the effects of SN were investigated in vitro using whole-cell patch-clamp recording, calcium imaging in PC12 cells and rat cortical neurons subjected to OGD-R.
  
  
  RESULTS
  Pretreatment with SN (10 and 30 mg·kg(-1) , i.p.) significantly decreased brain infarction and the overactivation of calcium-mediated events in rats subjected to 2 h ischaemia followed by 24 h reperfusion. Extracellular application of SN inhibited the currents mediated by acid-sensing ion channel 1a and L-type voltage-gated calcium channels, in the rat cultured neurons, in a concentration-dependent manner. These inhibitory effects contribute to the neuroprotection of SN against OGD-R and extracellular acidosis-induced cytotoxicity. More importantly, administration of SN (30 mg·kg(-1) , i.p.) at 1 and 2 h after cerebral ischaemia also decreased brain infarction and improved functional recovery.
  
  
  CONCLUSIONS
  SN exerts potent protective effects against ischaemic brain injury when administered before ischaemia or even after the injury. The inhibitory effects of SN on acid-sensing ion channel 1a and L-type calcium channels are involved in this neuroprotection.
authors.affiliation: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Wen-Ning
authors.initials: WN
authors.lastname: Wu
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Wu
authors.forename: Xiang-Long
authors.initials: XL
authors.lastname: Chen
authors.forename: Zui
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Gu
authors.forename: Yuan-Jian
authors.initials: YJ
authors.lastname: Yang
authors.forename: Qiu-Ju
authors.initials: QJ
authors.lastname: Xiong
authors.forename: Lan
authors.initials: L
authors.lastname: Ni
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Chen
mesh_terms: D062565:Acid Sensing Ion Channels; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016466:CHO Cells; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D018929:Cell Culture Techniques; D006224:Cricetinae; D003412:Cricetulus; D019610:Cytoprotection / Q000187:drug effects; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D008297:Male; D009019:Morphinans / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010100:Oxygen / Q000378:metabolism; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels
chemical_list: D062565:Acid Sensing Ion Channels; D020746:Calcium Channels, L-Type; D009019:Morphinans; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D015222:Sodium Channels; C009271:sinomenine; D005947:Glucose; D010100:Oxygen