title: Baicalin can scavenge peroxynitrite and ameliorate endogenous peroxynitrite-mediated neurotoxicity in cerebral ischemia-reperfusion injury.
abstract: BACKGROUND
  Baicalin is one of the principal flavonoids isolated from the dried root of Scutellaria baicalensis Georgi that has long been used to treat ischemic stroke. However, its neuroprotective mechanisms against cerebral ischemia injury are poorly understood.
  
  
  OBJECTIVE
  To explore the neuroprotective mechanisms of baicalin against cerebral ischemia reperfusion injury.
  
  
  METHODS
  In chemical systems, we conducted electron paramagnetic resonance (EPR) spin trapping experiments to evaluate the scavenging effects of baicalin on superoxide and nitric oxide, and mass spectrometry (MS) studies on the reaction of baicalin and peroxynitrite. In cellular experiments, we investigated the effects of baicalin against extraneous and endogenous peroxynitrite mediated neurotoxicity in SH-SY5Y cells treated with peroxynitrite donor, synthesized peroxynitrite and exposed to oxygen glucose deprivation and reoxygenation (OGD/RO) in vitro. Moreover, we studied the neuroprotective effects of baicalin by using a rat model of middle cerebral artery occlusion in vivo. FeTMPyP, a peroxynitrite decomposition catalyst, was used as positive control. Cell viability and apoptotic cell death was accessed by MTT assay and TUNEL assay respectively; 3-nitrotyrosine formation and infarction volume were detected by immunostaining experiments and TTC staining respectively.
  
  
  RESULTS
  Baicalin revealed strong antioxidant ability by directly scavenging superoxide and reacting with peroxynitrite. Baicalin protected the neuronal cells from extraneous and endogenous peroxynitrite-induced neurotoxicity. In ischemia-reperfused brains, baicalin inhibited the formation of 3-nitrotyrosine, reduced infarct size and attenuated apoptotic cell death, whose effects were similar to FeTMPyP.
  
  
  CONCLUSIONS
  Baicalin can directly scavenge peroxynitrite and the peroxynitrite-scavenging ability contributes to its neuroprotective mechanisms against cerebral ischemia reperfusion injury.
authors: School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 10 Sassoon Road, Hong Kong SAR, China; Research Centre of Heart, Brain, Hormone & Healthy Aging, The University of Hong Kong, 21 Sassoon Road, Hong Kong SAR, China. Electronic address: xmjcpu@gmail.com.
authors: Mingjing
authors: M
authors: Xu
authors: Xingmiao
authors: X
authors: Chen
authors: Yong
authors: Y
authors: Gu
authors: Tao
authors: T
authors: Peng
authors: Dan
authors: D
authors: Yang
authors: Raymond Chuen-Chuen
authors: RC
authors: Chang
authors: Kwok-Fai
authors: KF
authors: So
authors: Kejian
authors: K
authors: Liu
authors: Jiangang
authors: J
authors: Shen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009569:Nitric Oxide / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005419:Flavonoids; D018696:Neuroprotective Agents; D013481:Superoxides; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; C038044:baicalin
keywords: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; 3-NT; 3-morpholinosydnonimine; 3-nitrotyrosine; 4′,6-diamidino-2-phenylindole; 5-tert-butoxycarbonyl 5-methyl-1-pyrroline N-oxide; BBB; BMPO; Baicalin; Cerebral ischemia; DAPI; DMSO; DTPA; HX; MCAO; MGD; MMPs; MTT; N-methyl-D-glutamine-dithiocarbamate; OGD/RO; PDC; Peroxynitrite; ROS; SIN-1; TTC; TUNEL; Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling.; XO; blood brain barrier; diethylenetriamine pentaacetic acid; dimethyl sulfoxide; hypoxanthine; matrix metalloproteinases; middle cerebral artery occlusion; oxygen glucose deprivation plus reoxygenation; peroxynitrite decomposition catalyst; reactive oxygen species; triphenyl tetrazolium chloride; xanthine oxidase