Magnesium Lithospermate B Extracted from Salvia Miltiorrhiza, A Potential Substitute for Cardiac Glycosides

Tse-yu      Chung; Feng-yin      Li; Wen-Hua      Chiou; Jason      T.C. Tzen

Abstract

The therapeutic effect of cardiac glycosides lies in their reversible inhibition on the membrane-bound Na+/K+-ATPase in human myocardium. Unfortunately, the utilization of steroidal cardiac glycosides suffers some severe adverse side effects. Magnesium lithospermateB (MLB), a derivative of caffeic acid tetramer found in Danshen (Salvia miltiorrhiza), is suggested to provide a comparable cardiac therapeutic effect by effectively inhibiting Na+/K+-ATPase via the same molecular mechanism triggered by cardiac glycosides. Molecular modeling suggests that ouabain, a cardiac glycoside, and MLB presumably bind to the same extracellular pocket of the Na+/K+-ATPase. Moreover, MLB outperforms ouabain in cell toxicity, and thus has a great potential, with extensive clinical trials, to become a safe substitute for cardiac glycosides. Neuroprotective effects of cardiac glycosides and MLB against ischemic stroke have been observed, and cumulative data suggest that effective inhibitors of Na+/K+-ATPase in the brain may be potential drugs for the treatment of ischemic stroke. Taken together, recent studies on MLB seem to promote a paradigm shift of searching potential drugs for the treatment of cardiac diseases from steroid-like compounds to non-steroid ones.

Keywords: Cardiac glycoside, Danshen, magnesium lithospermate B, Na+/K+-ATPase, ouabain, Salvia miltiorrhiza, MLB, Cell toxicity, Plausible biosynthetic pathway, Rosmarinic acid