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Formoononetin is one kind of isoflavones which is contained in many herbs, such as Trifoliurn pratense L., Caulis Spatholobi.In this study, we investigated the protective effect of formoononetin on primary-cultured mouse cortical neurons injured by N-methyl-D-asparate (NMDA).After exposure of cortical neurons to 200 μM NMDA for 40 min, the cell viability decreased significantly, which was determined by MTT assay.However, pretreatment with 10 μM formoononetin for 12 h attenuated the cell apoptosis markedly.Westem blot analysis showed that formoononetin not only increased the expression of Bc1-2, but also attenuated the NMDA-induced up-regulation of Bax and suppressed the activation of caspase-3.Formoononetin could also improve NMDA-induced morphologic impairment which was detected by Hoechst/PI double fluorescent staining.To further evaluate neuron apoptosis, flow cytometry was performed.The results revealed that the number of apoptotic cells decreased remarkably in formoononetin-treating group.All the results demonstrated that formoononetin was capable of protecting pramiary-cultured cortical neurons from NMDA-induced neurotoxicity.According to this investigation, formoononetin has a good perspective to be a medicine treating NMDA-related neuronal diseases.