Promotion of axonal maturation and prevention of memory loss in mice by extracts of Astragalus mongholicus

Background and purpose: Neurons with atrophic neurites may remain alive and therefore may have the potential to regenerate even when neuronal death has occurred in some parts of the brain. This study aimed to explore effects of drugs that can facilitate the regeneration of neurites and the reconstruction of synapses even in severely damaged neurons. Experimental approach: We investigated the effects of extracts of Astragalus mongholicus on the cognitive defect in mice caused by injection with the amyloid peptide Aβ(25-35). We also examined the effect of the extract on the regeneration of neurites and the reconstruction of synapses in cultured neurons damaged by Aβ(25-35).Key results:A. mongholicus extract (1 g kg ^-1 day ^-1 for 15 days, p.o.) reversed Aβ(25-35)-induced memory loss and prevented the loss of axons and synapses in the cerebral cortex and hippocampus in mice. Treatment with Aβ(25-35) (10 μM) induced axonal atrophy and synaptic loss in cultured rat cortical neurons. Subsequent treatment with A. mongholicus extract (100 μg/ml) resulted in significant axonal regeneration, reconstruction of neuronal synapses, and prevention of Aβ(25-35)-induced neuronal death. Similar extracts of A. membranaceus had no effect on axonal atrophy, synaptic loss, or neuronal death. The major known components of the extracts (astragalosides I, II, and IV) reduced neurodegeneration, but the activity of the extracts did not correlate with their content of these three astragalosides. Conclusion and implications: A. mongholicus is an important candidate for the treatment of memory disorders and the main active constituents may not be the known astragalosides.