Rehmannia is a commonly used Chinese herb,which improves learning and memory.However,the crucial components of the signal transduction pathway associated with this effect remain elusive.Primary hippocampal neurons were cultured in vitro,insulted with high-concentration(1 × 10 –4 mol/L) corticosterone,and treated with 1 × 10 –4 mol/L mannotriose.Thiazolyl blue tetrazolium bromide assay and western blot analysis showed that hippocampal neuron survival rates and protein levels of glucocorticoid receptor,serum and glucocorticoid-regulated protein kinase,and brain-derived neurotrophic factor were all dramatically decreased after high-concentration corticosterone-induced injury.This effect was reversed by mannotriose,to a similar level as RU38486 and donepezil.Our findings indicate that mannotriose could protect hippocampal neurons from high-concentration corticosterone-induced injury.The mechanism by which this occurred was associated with levels of glucocorticoid receptor protein,serum and glucocorticoid-regulated protein kinase,and brain-derived neurotrophic factor. The crucial components of the signal transduction pathway associated with this effect remain elusive. Primary hippocampal neurons were cultured in vitro, insulted with high-concentration (1 × 10 -4 mol / L) corticosterone, and treated with 1 × 10 -4 mol / L mannotriose.Thiazolyl blue tetrazolium bromide assay and western blot analysis showed that hippocampal neuron survival rates and protein levels of glucocorticoid receptor, serum and glucocorticoid-regulated protein kinase, and brain-derived neurotrophic factor were all dramatically decreased after high-concentration corticosterone-to-injury injury. This effect could be explained by the fact that the mannotriose could protect hippocampal neurons from high-concentration corticosterone-induced injury. The mechanism by which this occurred was associated with levels of glucocorticoid receptor protein, ser um and glucocorticoid-regulated protein kinase, and brain-derived neurotrophic factor.