The natural therapeutic magnesium lithospermate B potently provides neuroprotective effects on cerebral ischemia/reperfusion injury in rats

J Ethnopharmacol. 2015 Mar 13:162:191-8. doi: 10.1016/j.jep.2014.12.048. Epub 2015 Jan 2.


Ethnopharmacological relevance: 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.

Materials and 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.

Keywords: Akt; Apoptosis; Ischemia/reperfusion; Magnesium lithospermate B; Magnesium lithospermate B (PubChem CID: 6918234); Salvia miltiorrhiza.

MeSH terms

  • Animals
  • Brain Ischemia / complications*
  • Chromones / pharmacology
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / pharmacology*
  • Infarction, Middle Cerebral Artery
  • Male
  • Molecular Structure
  • Morpholines / pharmacology
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / etiology
  • Reperfusion Injury / prevention & control*
  • Salvia miltiorrhiza / chemistry


  • Chromones
  • Drugs, Chinese Herbal
  • Morpholines
  • Neuroprotective Agents
  • lithospermate B
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one