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 toregenerate even when neuronal death has occurred in some parts of the brain. This study aimed to explore effects of drugs thatcan 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 micecaused by injection with the amyloid peptide Ab(25-35). We also examined the effect of the extract on the regeneration ofneurites and the reconstruction of synapses in cultured neurons damaged by Ab(25-35).

Key results: A. mongholicus extract (1 g kg
1 day
1 for 15 days, p.o.) reversed Ab(25-35)-induced memory loss and preventedthe loss of axons and synapses in the cerebral cortex and hippocampus in mice. Treatment with Ab(25-35) (10 mM) inducedaxonal atrophy and synaptic loss in cultured rat cortical neurons. Subsequent treatment with A. mongholicus extract (100 mg/ml) resulted in significant axonal regeneration, reconstruction of neuronal synapses, and prevention of Ab(25-35)-inducedneuronal 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 theextracts 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 mainactive constituents may not be the known astragalosides.