Wowzah! Why the hell aren't we using this stuff as a conitive enhancer? It doesn't appear to be expensive at that dosage. Even more uses here http://download.spri...52439c&ext=.pdf
http://www.nature.co.../srep00535.htmlThe 5XFAD mouse model reveals AD pathologies at an early age. Memory dysfunctions in the 5XFAD mice, including deficits in object recognition memory10, 11, spatial memory9 and contextual fear memory8, were detected at 4 months old. The present study showed for the first time that diosgenin administration improved the object recognition memory deficit in 5XFAD mice. Diosgenin administration inhibited several signs of neuronal degeneration, including presynaptic degeneration associated with amyloid plaques in the cortex, axonal degeneration associated with amyloid plaques in the cortex and hippocampus and PHF-tau expression associated with and distal to amyloid plaques in the cortex and hippocampus. In addition, amyloid plaques were decreased by diosgenin treatment. It was reported that the diosgenin derivative, caprospinol (diosgenin 3-caproate), reduced amyloid deposits and improved memory dysfunction in Aβ1-42-infused AD model rats17. Therefore, it is possible that the amyloid plaque decreasing effect of diosgenin results in the protection of axonal degeneration and the hyperphosphorylation of tau. However, diosgenin can enhance axonal growth in normal neurons (Figures 5 and 6) and can induce the regrowth of axons in Aβ-treated neurons following treatment (Figure 7). In addition, diosgenin shows no direct binding activity to Aβ33. These results indicate that diosgenin may contribute to axonal extension through a direct pathway, as well as through the amyloid plaque-lowering pathway. The approved anti-AD drug memantine caused no improvement in object recognition (Figure 1B), the degeneration of axons and presynapses (Figure 1D) or PHF-tau expression (Figures 2B and 2C), but it did reduce amyloid plaques (Figure 1C). The reduction of amyloid plaques by memantine was previously reported in the AD model Tg2576 mice at 10 and 20 mg/kg34 and APP/PS1 mice at 10 mg/kg35, although the mechanism by which it occurred is unknown. Conflicting results have been reported concerning memory improvement due to memantine. Fear-conditioned memory is not improved by treatment with 10 or 20 mg/kg memantine for 6 months in Tg2576 mice, despite the reduction of amyloid plaques34. The administration of 10 mg/kg memantine for 4 months improved object recognition in APP/PS1 mice35, but the administration of 10 mg/kg memantine for 1 week did not affect the spatial memory deficit in APP23 mice36. Surprisingly, memantine treatment significantly increased the number of degenerated axons in the dentate gyrus of Tg2576 mice34. Additionally, in our study, memantine increased the number of degenerated axons in the hippocampus (Figure 2). These results suggest that memantine may have both neuroprotective and neurotoxic effects. In our previous study, a higher dose of diosgenin (100 μmol/kg) was administered to 5XFAD mice (male, 79 months old) by i.p. injection for 19 days. In object recognition test, diosgenin-treated 5XFAD mice showed memory improvement. Since the efficacy of diosgenin at a dose of 100 μmol/kg was almost same to that of 10 μmol/kg diosgenin, we consider that 10 μmol/kg diosgenin is enough to improve memory dysfunction.
http://www.ncbi.nlm....2837815/relatedDiosgenin-induced cognitive enhancement in normal mice is mediated by 1,25D₃-MARRS.
AuthorsTohda C, et al. Show allJournal
Sci Rep. 2013 Dec 2;3:3395. doi: 10.1038/srep03395.
Affiliation
Abstract
We previously reported that diosgenin, a plant-derived steroidal sapogenin, improved memory and reduced axonal degeneration in an Alzheimer's disease mouse model. Diosgenin directly activated the membrane-associated rapid response steroid-binding receptor (1,25D₃-MARRS) in neurons. However, 1,25D₃-MARRS-mediated diosgenin signaling was only shown in vitro in the previous study. Here, we aimed to obtain in vivo evidence showing that diosgenin signaling is mediated by 1,25D₃-MARRS in the mouse brain. Diosgenin treatment in normal mice enhanced object recognition memory and spike firing and cross-correlation in the medial prefrontal cortex and hippocampal CA1. In diosgenin-treated mice, axonal density and c-Fos expression was increased in the medial prefrontal and perirhinal cortices, suggesting that neuronal network activation may be enhanced. The diosgenin-induced memory enhancement and axonal growth were completely inhibited by co-treatment with a neutralizing antibody for 1,25D₃-MARRS. Our in vivo data indicate that diosgenin is a memory-enhancing drug and that enhancement by diosgenin is mediated by 1,25D₃-MARRS-triggered axonal growth.