Neuroprotective effects of hydroxysafflor yellow A against excitotoxic neuronal death partially through down-regulation of NR2B-containing NMDA receptors.

Hydroxysafflor yellow A (HSYA) is a component of the flower Carthamus tinctorius L. that elicits neuroprotective effects in vivo and in vitro. The purpose of this study was to investigate pharmacological properties of HSYA on neurotoxicity of glutamate in primary cultured rat cortical neurons along with its possible mechanism of action. After challenge with N-methyl-d-aspartate (NMDA, 100 μM) for 30 min, loss of cell viability and excessive apoptotic cell death were observed in cultured cortical neurons. However, the excitotoxic neuronal death was attenuated markedly by HSYA treatment. Western blot analysis revealed that HSYA decreased expression of Bax and rescued the balance of pro-and anti-apoptotic proteins. In addition, HSYA significantly reversed up-regulation of NR2B-containing NMDA receptors by exposure to NMDA, while it did not affect the expression of NR2A-containing NMDA receptors. These finding suggest that HSYA protects cortical neurons, at least partially, from inhibiting the expression NR2B-containing NMDA receptors and by regulating Bcl-2 family.