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

Abstract

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 . We also examined the effect of the extract on the regeneration of neurites and the reconstruction of synapses in cultured neurons damaged by . Key results: A. mongholicus extract (1 g kg À1 day À1 for 15 days, p.o.) reversed Ab(25-35)-induced memory loss and prevented the loss of axons and synapses in the cerebral cortex and hippocampus in mice. Treatment with Ab(25-35) (10 mM) induced axonal 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)-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. Keywords: dementia; axon; synapse; neuronal death; Astragali radix; Astragalus mongholicus; astragalosides; morris water maze; Abbreviations: NF-H, neurofilament-H; NGF, nerve growth factor IntroductionIn addition to the death of neurons, atrophy of neurites and loss of synapses are the major causes of dysfunctions of the brain including Alzheimer's (DeKosky and Scheff, 1990;Terry et al., 1991;Dickson and Vickers, 2001), Parkinson's, Huntington and Creutzfeldt-Jakob diseases (Jackson et al., 1995;Liberski and Budka, 1999;Mattila et al., 1999). 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. We have hypothesized that reconstructing neuronal networks in the injured brain is essential for the recovery of brain function . To reconstruct neuronal networks, neurites must be regenerated and synapses must be reconstructed. In the current studies, we explored the in vitro and in vivo effects of drugs that can facilitate the regeneration of neurites and the reconstruction of synapses even in severely damaged neurons.Astragali radix (the root of Astragalus mongholicus Bunge or A. membranaceus Bunge) is used mainly as a tonic agent in traditional Chinese and Japanese Kampo medicine. A few reports show that Astragali Radix extract or its components can affect brain function. For example...

Astragaloside IV rescues MPP+-induced mitochondrial dysfunction through upregulation of methionine sulfoxide reductase A

“…1A. AS-IV has comprehensive pharmacological functions, including anti-inflammatory and antioxidative activity, and is able to reduce infarct size and improve post-ischemic brain function (20)(21)(22). However, few studies have investigated whether AS-IV prevents mitochondrial dysfunction via MsrA.…”

Two New Cycloartane Saponins from the Roots of Astragalus membranaceus

“…Astramembranoside 6 Hz, H-1Љ) were observed, indicative of the presence of two b-linked sugar units. The sugar was identified as glucose by acid hydrolysis and TLC comparison with an authentic sample.…”

“…(Leguminosae) has long been one of the most important tonic herbs used in traditional Chinese medicine. Studies of its pharmacology and clinical use have demonstrated that Astragali Radix has many biological functions, including hepatoprotection, 3,4) neuroprotection against ischemic brain injury, 5,6) immunologic properties, 7-9) cardiotonic 10,11) and antiaging activities, 12) gastroprotection, 13) adjuvant 14) and antitumor effects, 15,16) antiinflammatory effects, 17,18) and stimulation of the growth of new tissues. 19,20) The major bioactive components of A. membranaceus are triterpene saponins and isoflavonoids.…”

Suppressive Actions of Astragali Radix (AR) Ethanol Extract and Isolated Astragaloside I on HCl/ethanol-Induced Gastric Lesions

“…(Leguminosae), has been used as one of the most important tonic herbs in traditional medicine. Pharmacological studies of AR have demonstrated that AR possesses many biological functions, including hepatoprotective (Ríos et al, 1997;Gui et al, 2006), neuroprotective effect against ischemic brain injury (Luo et al, 2004;Tohda et al, 2006), immunological properties (Shao et al, 2004;Li et al, 2007;Cho et al, 2007a), cardiotonic (Zhang et al, 2006a;Zhang et al, 2006b), antiaging activities (Lei et al, 2003), gastroprotective (Navarrete et al, 2005), adjuvant (Rajput et al, 2007), antitumor effects (Cho et al, 2007b;Tin et al, 2007), anti-inflammatory (Zhang et al, 2003), and the growth of new tissues (Cheng et al, 2006;Choi et al, 2007).…”