Tzen Jason Tc, Jinn Tzyy-Rong, Chen Yi-Ching, Li Feng-Yin, Cheng Fu-Chou, Shi Li-Shian, She Hank Kh, Chen Balance Cm, Hsieh Vic, Tu Mu-Lin
Graduate Institute of Biotechnology, National Chung Hsing University, Taichung, Taiwan 402 China.
Acta Pharmacol Sin. 2007 May;28(5):609-15. doi: 10.1111/j.1745-7254.2007.00544.x.
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.
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.
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.
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.
研究从丹参（丹参干燥根）中提取的丹酚酸B（MLB）是否可能通过与强心苷（如哇巴因和地高辛）引发的相同分子机制，作为这种传统中药心脏治疗作用的活性成分。此外，我们想测试MLB是否能像强心苷一样对缺血性中风提供神经保护作用。
分析了MLB和哇巴因之间的化学结构和分子构型的相似性。检测并比较了MLB和哇巴因对市售产品以及大鼠脑和心脏组织纯化膜组分中Na(+)，K(+) -ATP酶活性的抑制效力。还使用基于大脑皮层切片的检测模型评估了MLB对缺血性中风的神经保护作用。
观察到重量约为哇巴因一半剂量的MLB对市售Na(+)，K(+) -ATP酶有剂量依赖性抑制作用。哇巴因和MLB对从大鼠组织纯化的质膜Na(+)，K(+) -ATP酶活性的抑制也观察到了这种相对效力，尽管这两种抑制剂在这些粗提物中的活性略低。在缺血沙土鼠脑中，与对照组相比，MLB治疗后通过2,3,5-三苯基氯化四氮唑染色显示梗死面积显著减少约55%。
这些结果明显表明，丹参的心脏治疗作用至少部分应归因于MLB对Na(+)，K(+) -ATP酶的有效抑制，并且MLB为遭受局灶性缺血和再灌注的沙土鼠提供抗缺血神经保护作用。
