N-methyl-D-aspartate receptor antagonist activity in traditional Chinese stroke medicines

Traditional Chinese medicine (TCM) has a long history in stroke therapy and its therapeutic efficacy has been confirmed by clinical studies. The molecular basis of the neuroprotective effects is unknown. We wondered whether or not the neuroprotective effect of TCMs might be due to their N-methyl-D-aspartate (NMDA) receptor (NMDAR) antagonist properties. We used the patch-clamp technique to screen 22 TCM stroke drugs for NMDAR antagonist activity in cultured cortical neurons. The drugs were also screened for their ability to abate NMDA-induced neurotoxicity. Aqueous extracts of Scutellaria baicalensis, Stephania tetrandra, and Salvia miltiorrhiza blocked currents induced by NMDA (200 microM, 10 microM glycine, 0 Mg2+) at a holding potential of -80 mV by 83.45+/-4.34, 38.65+/-7.50, and 52.97+/-1.78%, respectively. The block of the NMDA-evoked currents was voltage-dependent and showed a negative slope conductance reminiscent of Mg2+. Atomic absorption spectrophotometry revealed the presence of 12.5, 2, and 8.7 mM Mg2+ in the extracts of S. baicalensis,S. tetrandra, and S. miltiorrhiza, respectively. None of these extracts blocked NMDA-induced neuronal death. The Uncaria rhynchophylla extract blocked NMDA-evoked currents by 54.98+/-8.61% even at +60 mV and reduced NMDA-induced neuronal death by 59.13+/-3.52%. NMDAR antagonist activity may underlie the neuroprotective effects of this TCM. Some TCM drugs may exert therapeutic effects due to their Mg2+ content.