OBJECTIVE To investigate the protective effect of Noble dendrobium polysaccharides (NDP) on inflammatory fac tors, which are produced and released by l ipopolysaecharide (LPS)-activated rat cerebral microglia, and to explore the pro tective mechanisms of NDP against LPS-induced neuron damage.METHODS The whole brains of 1 or 2-day-old mice was dis sected, and microglia were isolated and cultured.Before expo sure to LPS neurotoxicity, cells were treated with NDP (24 h),and the microglia-conditioned medium (MCM) collected.Pri mary neuronal cultures were supplemented with the 24 h MCM.The morphology and density of neuronal synapses were observed by immunofluorescence;the production of NO was detected with the Griess reagent;the level of tumor necrosis factor-α (TNF α) was assessed by ELISA;the degree of neuronal apoptosis was examined with Hoechst 33258.RESULTS The hippocampal neurons were apparently damaged by the supernatant of activated MCM, and the morphology of the neurons changed significantly.Compared to control group, the level of NO was elevated and the expression level of TNF-α protein was significantly increased,and the apoptosis was induced in neurons.NDP improved synap tic morphology and increase synapses density, depress the high level of NO, inhibited the up-expression of TNF-α protein by LPS, and decreased neuronal apoptosis.CONCLUSION NDP may significantly inhibit the activation of microglia induced by LPS and reduce the release of inflammatory factors.These results showed that NDP exert neuroprotection through depressing the actived microglia.