Effect of sodium tanshinone IIA sulfonate in the rabbit myocardium and on human cardiomyocytes and vascular endothelial cells.
Sodium tanshinone IIA sulfonate (STS) is a derivative of tanshinone IIA. The latter is a pharmacologically active component isolated from the rhizome of the Chinese herb Salvia miltiorrhiza. Liquid chromatographically pure STS was found to reduce myocardial infarct size by 53.14 +/- 22.79% relative to that in the saline control in a rabbit 1 hr-ischemia and 3 hr-reperfusion model. This effect was comparable to that of Trolox (a better characterized antioxidant serving as a reference cytoprotector), which salvaged the myocardium in the same infarct model by 62.13 +/- 18.91%. Also, like Trolox, STS did not inhibit oxygen uptake by xanthine oxidase (XO), a key enzyme in free radical generation. However, in contrast to Trolox, STS significantly prolonged the survival of cultured human saphenous vein endothelial cells but not human ventricular myocytes in vitro when these cells were separately exposed to XO-generated oxyradicals. Note that the endothelium is recognized to be a key site of oxidant generation and attack. Our findings in vitro and in vivo support the interpretation that STS is a cardioprotective substance, and that it may exert a beneficial effect on the clinically important vascular endothelium.
Wu
T W
TW
Department of Clinical Biochemistry, University of Toronto, Ontario, Canada.
Zeng
L H
LH
Fung
K P
KP
Wu
J
J
Pang
H
H
Grey
A A
AA
Weisel
R D
RD
Wang
J Y
JY
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006321:Heart / Q000187:drug effects*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009206:Myocardium / Q000166:cytology; D010616:Phenanthrenes / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits; D016339:Spectrometry, Mass, Fast Atom Bombardment; D014969:Xanthine Oxidase / Q000378:metabolism
D000975:Antioxidants; D002839:Chromans; D004365:Drugs, Chinese Herbal; D010616:Phenanthrenes; C024894:tanshinone II A sodium sulfonate; D014969:Xanthine Oxidase; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid