title: The natural therapeutic magnesium lithospermate B potently provides neuroprotective effects on cerebral ischemia/reperfusion injury in rats.
abstract: BACKGROUND
  Salvia miltiorrhiza, a perennial plant in the genus Salvia and popularly known as "Danshen", is highly valued for its roots in traditional Chinese medicines (TCMs). It has widely used for the treatment of cerebrovascular and cardiovascular diseases in China. Recently, the cerebral protection of magnesium lithospermate B (MLB), a working extract from Salvia miltiorrhiza, has received more attention. Here, we investigated the therapeutic effects of MLB on cerebral ischemia/reperfusion (CI/R) injury using the middle cerebral artery occlusion (MCAO) model in rats.
  
  
  METHODS
  Male Sprague-Dawley rats were subjected to CI/R using a thread to occlude the right middle cerebral artery. After 2h of cerebral ischemia, the middle cerebral artery was reperfused for 24 h. Rats were injected with different doses of MLB (15, 30 and 60 mg/kg). Infarct zones, neurological deficit scores, brain water content, glutamate levels and protein expressions were evaluated after 24h of reperfusion.
  
  
  RESULTS
  We found that MLB treatment of rats exposed to focal CI/R decreased neurological deficit scores, brain water content, glutamate levels and cerebral infarct zones. We also demonstrated that MLB can inhibit CI/R injury-induced activation of caspase-3, a marker of apoptosis. This protection by MLB against CI/R injury was accompanied by an upregulation of p-Akt in the ischemic hemisphere. Furthermore, the MLB-induced protection was prevented by treatment with a PI3K inhibitor (LY-294002).
  
  
  CONCLUSIONS
  The data in the present study suggest a potential protective role of MLB against CI/R injury in rats. The salient finding of the present study is that this protective effect of MLB is likely mediated through an Akt-dependent pathway.
authors.affiliation: Department of Urinary Urology, General Hospital of Shenyang Military Region, Shenyang 110840, China.
authors.forename: Zhi-qiang
authors.initials: ZQ
authors.lastname: Cao
authors.affiliation: Department of Pharmacy, Xi'an Mental Health Center, Institute of Mental Health, Xi'an Medical University, Xi'an 710061, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Quan
authors.affiliation: Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Shuang-xing
authors.initials: SX
authors.lastname: Hou
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Shan-bo
authors.initials: SB
authors.lastname: Ma
authors.affiliation: Department of Medical Statistics, School of Preventive Medicine, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Urinary Urology, General Hospital of Shenyang Military Region, Shenyang 110840, China. Electronic address: syzylixin@126.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications*; D002867:Chromones / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D015394:Molecular Structure; D009025:Morpholines / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D027561:Salvia miltiorrhiza / Q000737:chemistry
chemical_list: D002867:Chromones; D004365:Drugs, Chinese Herbal; D009025:Morpholines; D018696:Neuroprotective Agents; C061091:lithospermate B; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
keywords: Akt; Apoptosis; Ischemia/reperfusion; Magnesium lithospermate B; Magnesium lithospermate B (PubChem CID: 6918234); Salvia miltiorrhiza