AIM: To study the effects of puerarin (Pue) against injury of cultured neurons by sodium glutamate (Glu). METHODS: Neuronal damage induced by Glu, N-methyl-D-aspartate (NMDA), and kainic acid (KA), as well as the actions of Pue and some excitatory amino acid antagonists (EAAA), were measured by determining the leakage of lactate dehydrogenase (LDH) from nerve cells. RESULTS: The 24-h leakage of LDH was increased from cells exposed either to Glu 100 and 500 mu mol.L-1 for 15 min (from 20 +/- 4 kU/g protein in control group to 35 +/- 3 kU/g protein in Glu 100 mu mol.L-1 group and to 46 +/- 6 kU/g protein in Glu 500 mu mol.L-1 group) or to NMDA 500 mu mol.L-1 or KA 500 mu mol.L-1 for 45 min (from 19 +/- 4 kU/g protein in control group to 27 +/- 3 kU/g protein in NMDA group and to 30 +/- 5 kU/g protein in KA. group). Pre and post-treatment with Pue (100 mu mol.L-1) decreased the leakage of LDH, which was similar to the effects of EAAA kynurenic acid (from 35 +/- 3 kU/g protein in Glu 100 mu mol.L-1 to 20 +/- 5 kU/g protein in kynurenic acid group and to 22 +/- 3 kU/g protein in Pue group), DL-2-amino-5-phosphonovaleric acid (APV) (from 27 +/- 3 kU/g protein in NMDA damaged group to 183 kU/g protein in APV group and to 19 +/- 5 kU/g protein in Pue group) or 6,7-dinitroquinoxaline-2,3(1H, 4H)-diane (DNQX) (from 30 +/- 5 kU/g protein in KA damaged control to 22 +/- 5 kU/g protein in DNQX group and to 20 +/- 4 kU/g protein in Pue group). Post-treatment with Pue (100 mu mol.L-1) was able to reduce 24-h leakage of LDH from neurons expos ed to Glu 100 mu mol.L-1 for 15 min (from 35 +/- 3 kU/g protein to 27 1:4 kU/g protein). CONCLUSION: Pue had protective effects on neurons damaged by Glu, NMDA, or KA.