Magnesium lithospermate B possesses inhibitory activity on Na+,K+-ATPase and neuroprotective effects against ischemic stroke.
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.
Tzen
Jason Tc
JT
Graduate Institute of Biotechnology, National Chung Hsing University, Taichung, Taiwan 402 China. TCTZEN@dragon.nchu.edu.tw
Jinn
Tzyy-Rong
TR
Chen
Yi-Ching
YC
Li
Feng-Yin
FY
Cheng
Fu-Chou
FC
Shi
Li-Shian
LS
She
Hank Kh
HKh
Chen
Balance Cm
BC
Hsieh
Vic
V
Tu
Mu-Lin
ML
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
D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; C061091:lithospermate B; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase