title: Salvianolic acid A inhibits calpain activation and eNOS uncoupling during focal cerebral ischemia in mice.
abstract: BACKGROUND
  Salvianolic acid A (SAA) is obtained from Chinese herb Salviae Miltiorrhizae Bunge (Labiatae), has been reported to have the protective effects against cardiovascular and neurovascular diseases.
  
  
  OBJECTIVE
  The aim of present study was to investigate the relationship between the effectiveness of SAA against neurovascular injury and its effects on calpain activation and endothelial nitric oxide synthase (eNOS) uncoupling.
  
  
  METHODS
  SAA or vehicle was given to C57BL/6 male mice for seven days before the occlusion of middle cerebral artery (MCAO) for 60min.
  
  
  METHODS
  High-resolution positron emission tomography scanner (micro-PET) was used for small animal imaging to examine glucose metabolism. Rota-rod time and neurological deficit scores were calculated after 24h of reperfusion. The volume of infarction was determined by Nissl-staining. The calpain proteolytic activity and eNOS uncoupling were determined by western blot analysis.
  
  
  RESULTS
  SAA administration increased glucose metabolism and ameliorated neuronal damage after brain ischemia, paralleled with decreased neurological deficit and volume of infarction. In addition, SAA pretreatment inhibited eNOS uncoupling and calpain proteolytic activity. Furthermore, SAA inhibited peroxynitrite (ONOO-) generation and upregulates AKT, FKHR and ERK phosphorylation.
  
  
  CONCLUSIONS
  These findings strongly suggest that SAA elicits a neurovascular protective role through the inhibition of eNOS uncoupling and ONOO-formation. Moreover, SAA attenuates spectrin and calcineurin breakdown and therefore protects the brain against ischemic/reperfusion injury.
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Qaisar
authors.initials: Q
authors.lastname: Mahmood
authors.affiliation: Department of PET/CT Center, The First Affiliated Hospital, School of Medicine, Zhejiang University Zhejiang 310003, China.
authors.forename: Guang-Fa
authors.initials: GF
authors.lastname: Wang
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wu
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Chang-Xin
authors.initials: CX
authors.lastname: Zhou
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China.
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Yang
authors.affiliation: Department of Neurology, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, Zhejiang 310009, China.
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Liu
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China. Electronic address: changhuahan@zju.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Han
authors.affiliation: Department of PET/CT Center, The First Affiliated Hospital, School of Medicine, Zhejiang University Zhejiang 310003, China. Electronic address: Zhaokuizh@163.com.
authors.forename: Kui
authors.initials: K
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002109:Caffeic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D002154:Calpain / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D020244:Infarction, Middle Cerebral Artery / Q000517:prevention & control; D007773:Lactates / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010766:Phosphorylation; D008517:Phytotherapy; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D015854:Up-Regulation
chemical_list: D002109:Caffeic Acids; D004365:Drugs, Chinese Herbal; D007773:Lactates; D018696:Neuroprotective Agents; C066201:salvianolic acid A; D052250:Nitric Oxide Synthase Type III; D002154:Calpain
keywords: Neurovascular protection; Oxidative stress; Salvianolic acid A; Stroke; eNOS uncoupling