Sominone Improves Memory Impairments and Increases Axonal Density in Alzheimer's Disease Model Mice, 5XFAD

Abstract

Previously we showed that steroidal sapogenin, sominone improved memory after a single i.p. injection into normal mice. However, it had not been reported that sominone could recover memory deficits in a severe Alzheimer's disease (AD) model animal. Therefore, we aimed to investigate that sominone improved memory impairments in the 5XFAD mouse, model for AD. In the current study, we used sominone that we had synthesized. 5XFAD mice were given 10 μmol/kg sominone intraperitoneally for 9 days. In addition to object recognition memory, axonal density, amyloid plaque number, and activated microglia in the brain were evaluated. Sominone treatment significantly improved object recognition memory compared with vehicle control treatment. Sominone treatment significantly enhanced axonal densities in the frontal cortex and parietal cortex but had no effects on amyloid plaque number and activated microglia. In cultured cortical neurons, the axonal length was significantly reduced by Aβ(1-42) treatment. However, that was markedly recovered 5 days after the treatment with 1 μM sominone. Neuronal loss was not observed in the cortex and hippocampus of 5XFAD mice at 6-8 months of age. These results suggest that memory deficits in AD may be improved by sominone independently of reducing amyloid plaques and neuroinflammation.

New Age Therapy for Alzheimer’s Disease by Neuronal Network Reconstruction

“…42) Memory deficits in 5XFAD mice were demonstrated after 4 months old by contextual fear conditioning 43) and Y-maze test. 41) We additionally confirmed impairment of spatial memory 44) and object recognition memory 45,46) in these mice.…”

Effects of Ashwagandha (Roots of <i>Withania somnifera</i>) on Neurodegenerative Diseases

“…administration of sominone increased axonal density in the brain and improved object recognition memory impairment. 27) These results suggest that withanoside IV is metabolized to its active principle sominone after oral administration, which subsequently induces marked recovery of neurites, synapses, and memory. These data suggest that withanoside IV and its metabolite sominone are potential drugs against Alzheimer's disease.…”

“…Further studies of Ashwagandha will probably contribute to resolving an urgent unmet medical need: efficacious treatments that may offer cure of neurodegenerative diseases. 17) Memory improvement 38) Neuroprotective effects in vitro 33,35) Aβ clearance in vivo 38) Withanolide A Neurite outgrowth in vitro 18,19) Axonal regeneration and synaptic reconstruction in vitro and in vivo 21) Memory improvement 21) Upregulation of BACE1, ADAM10 and IDE in vitro 31) Withanoside IV Neurite outgrowth in vitro 18,19) Axonal regeneration and synaptic reconstruction in vitro and in vivo 22) Memory improvement 22) Withanoside VI Neurite outgrowth in vitro 18,19) Axonal regeneration and synaptic reconstruction in vitro and in vivo 23) Memory improvement 23) Sominone Axonal regeneration and synaptic reconstruction in vitro 22) Axonal growth in vivo 28) Memory improvement 27) and memory enhancement 28) Denosomin Axonal regeneration and neuroprotective effect in vitro 45) Withanone Neuroprotective effects in vitro 35) Spinal cord injury Withanoside IV Axonal growth in vivo and functional recovery 43) Denosomin Axonal growth in vivo and functional recovery 45) Parkinson's disease Extract Anti-oxidant effect in vivo [55][56][57][58][59] Neuroprotective effect in vivo 55,59) Functional recovery [55][56][57][58][59] Huntington's disease Extract Anti-oxidant ef...…”

Kamikihi-to (KKT) Rescues Axonal and Synaptic Degeneration Associated with Memory Impairment in a Mouse Model of Alzheimer's Disease, 5XFAD

“…In addition to memory deficits in 5XFAD shown by contextual fear conditioning (Ohno, 2009) and Y-maze , we clarified impairments of spatial memory (Urano & Tohda, 2010) and object recognition memory (Joyashiki, Matsuya, & Tohda, 2011) in 5XFAD. Therefore, the aim of this study is to investigate the effects of KKT on memory deficits in 5XFAD.…”