Diosgenin is an exogenous activator of 1,25D3-MARRS/Pdia3/ERp57 and improves Alzheimer's disease pathologies in 5XFAD mice

Abstract

The aim of this study was to investigate the effects and the mechanism of diosgenin, a famous plant-derived steroidal sapogenin, on memory deficits in Alzheimer's disease (AD) model mice. Diosgenin-treated 5XFAD mice exhibited significantly improved performance of object recognition memory. Diosgenin treatment significantly reduced amyloid plaques and neurofibrillary tangles in the cerebral cortex and hippocampus. Degenerated axons and presynaptic terminals that were only observed in regions closely associated with amyloid plaques were significantly reduced by diosgenin treatment. The 1,25D3-membrane-associated, rapid response steroid-binding protein (1,25D3-MARRS) was shown to be a target of diosgenin. 1,25D3-MARRS knockdown completely inhibited diosgenin-induced axonal growth in cortical neurons. Treatment with a neutralizing antibody against 1,25D3-MARRS diminished the axonal regeneration effect of diosgenin in Aβ(1–42)-induced axonal atrophy. This is the first study to demonstrate that the exogenous stimulator diosgenin activates the 1,25D3-MARRS pathway, which may be a very critical signaling target for anti-AD therapy.

Consumption of Japanese Yam Improves Lipid Metabolism in High-Cholesterol Diet-Fed Rats

“…Recently, 1,25D3-membraneassociated, rapid response steroid-binding protein (1,25D3-MARRS) was identified as a target protein for Dio. Moreover, Tohda et al reported that Dio may function as an exogenous stimulator of 1,25D3-MARRS that induces axonal growth and regrowth of neurons (6). Hence, Dio may act on critical signaling pathways as a therapy for Alzheimer's disease.…”

Role of the 1,25D3-membrane-associated, rapid response steroid binding receptor in calcium and phosphate uptake and disease states

“…One such is diosgenin, a plant-derived steroidal sapogenin. Mice treated with diosgenin significantly reduced amyloid plaques and neurofibrillary tangles in the cerebral cortex and hippocampus 29 . More importantly, 1,25D₃-MARRS was shown to be a target of diosgenin and 1,25D₃-MARRS knockdown completely inhibited diosgenin-induced axonal growth in cortical neurons.…”

The Effect of Crude Diosgenin Extract from Purple and Yellow Greater Yams (Dioscorea alata L.) on the Lipid Profile of Dyslipidemia Rats

“…Steroids are lipophilic and thereby have the potential to interact with hydrophobic compounds (Manrique-Moreno et al, 2014). Liberation of diosgenin from its binding compounds is difficult because diosgenin binds to sugars (Rahu and Rao, 2012) and can interact with proteins (Tohda et al, 2012;Manivannan et al, 2013). Therefore, impurities in the crude extract of diosgenin may consist of complex compounds.…”