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 ∼9 mM 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 ∼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 ∼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.