title: Magnesium lithospermate B possesses inhibitory activity on Na+,K+-ATPase and neuroprotective effects against ischemic stroke.
abstract: OBJECTIVE
  To examine if magnesium lithospermate B (MLB) extracted from Danshen, the dried roots of Salvia miltiorrhiza, may act as an active component responsible for the cardiac therapeutic effect of this traditional Chinese herb via the same molecular mechanism triggered by cardiac glycosides, such as ouabain and digoxin. Moreover, we wanted to test if MLB may provide neuroprotection against ischemic stroke as observed for cardiac glycosides.
  
  
  METHODS
  Similarity in the chemical structure and molecular configuration between MLB and ouabain was analyzed. The inhibition potency of MLB and ouabain on Na( +),K( +) -ATPase activity of a commercial product, as well as in purified membrane fractions from rat brain and heart tissues, was examined and compared. Neuroprotective effect of MLB against ischemic stroke was also evaluated using a cortical brain slice-based assay model.
  
  
  RESULTS
  Dose-dependent inhibition on the commercial Na( +),K( +)-ATPase equivalent to that for ouabain was observed for MLB of approximately half dosage by weight. This relative potency of ouabain and MLB was also observed for their inhibition on Na( +),K( +)-ATPase activity of plasma membrane purified from rat tissues, although these 2 inhibitors exhibited somewhat lower competence in these crude extracts. In ischemic gerbil brains, post-treatment with MLB significantly reduced the infarct size, visualized by 2,3,5-triphenyltetrazolium chloride staining, by approximately 55% when compared with the control group.
  
  
  CONCLUSIONS
  These results evidently suggest that the cardiac therapeutic effect of Danshen should be at least partly attributed to the effective inhibition of Na( +),K( +)-ATPase by MLB, and that MLB provides anti-ischemic neuroprotection in gerbils subjected to focal ischemia and reperfusion.
authors: Graduate Institute of Biotechnology, National Chung Hsing University, Taichung, Taiwan 402 China. TCTZEN@dragon.nchu.edu.tw
authors: Jason Tc
authors: JT
authors: Tzen
authors: Tzyy-Rong
authors: TR
authors: Jinn
authors: Yi-Ching
authors: YC
authors: Chen
authors: Feng-Yin
authors: FY
authors: Li
authors: Fu-Chou
authors: FC
authors: Cheng
authors: Li-Shian
authors: LS
authors: Shi
authors: Hank Kh
authors: HKh
authors: She
authors: Balance Cm
authors: BC
authors: Chen
authors: Vic
authors: V
authors: Hsieh
authors: Mu-Lin
authors: ML
authors: Tu
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004365:Drugs, Chinese Herbal / Q000378:metabolism / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000378:metabolism; D016166:Free Radical Scavengers / Q000378:metabolism / Q000627:therapeutic use; D005849:Gerbillinae; D006801:Humans; D008297:Male; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000378:metabolism / Q000627:therapeutic use; D010042:Ouabain / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; C061091:lithospermate B; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase