Magnesium as NMDA receptor blocker in the traditional Chinese medicine Danshen

Aqueous extracts of the traditional Chinese medicine Danshen, the dried roots of Salvia miltiorrhiza Bunge (Labiatae), blocked N-methyl-D-aspartate (NMDA) evoked currents in cerebrocortical neurons in vitro. The block of the NMDA-evoked currents was voltage dependent and showed the negative slope conductance reminiscent of the effect of Mg2+ ions. Atomic absorption spectrophotometry (AAS) revealed that aqueous Danshen extracts contained approximately 9mM magnesium. Fractionation of the extracts by high performance liquid chromatography followed by patch clamp recording and AAS indicated that magnesium ions were present in two distinct fractions. One fraction contained approximately 5 mM magnesium and blocked NMDA-induced currents indicating that it contained mostly free Mg2+ ions, while a second fraction did not possess NMDA antagonist activity despite the presence of approximately 4 mM magnesium suggesting that Mg2+ in this fraction was mostly chelated. Following removal of the free Mg2+ by ion exchange chromatography, the previously observed block of the NMDA-induced currents was abolished. These data demonstrate that Danshen contains both free and chelated Mg2+. Free Mg2+ ions account for the NMDA antagonist activity of Danshen in vitro.