Abstract
Diosgenin, a yam-derived compound, was found to facilitate the repair of axonal atrophy and synaptic degeneration and improve memory dysfunction in a transgenic mouse model of Alzheimer’s disease (AD). It was also found to enhance neuronal excitation and memory function even in normal mice. We hypothesized that diosgenin, either isolated or in an extract, may represent a new category of cognitive enhancers with essential activities that morphologically and functionally reinforce neuronal networks. This study aimed to investigate the effects of a diosgenin-rich yam extract on cognitive enhancement in healthy volunteers. For this placebo-controlled, randomized, double-blind, crossover study, 28 healthy volunteers (age: 20–81 years) were recruited from Toyama Prefecture, Japan, and was randomly assigned to receive either a yam extract or placebo. Preliminary functional animal experiments indicated that an oil solvent mediated the most efficient distribution of diosgenin into the blood and brain after oral administration, and was a critical factor in the cognitive benefits. Therefore, test samples (placebo and yam extract) were prepared with olive oil and formulated as soft capsules. The intake period was 12 weeks, and a 6-week washout period separated the two crossover intake periods. The Japanese version of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) test was used for neurocognitive assessment, and the adverse effects were monitored through blood testing. Diosgenin-rich yam extract consumption for 12 weeks yielded significant increases in total RBANS score. Among the 12 individual standard cognitive subtests, diosgenin-rich yam extract use significantly improved the semantic fluency. No adverse effects were reported. The diosgenin-rich yam extract treatment appeared to safely enhance cognitive function in healthy adults.
Highlights
Alzheimer’s disease (AD) is a chronic, progressive, and untreatable neurodegenerative disorder characterized by the accumulation of amyloid β (Aβ) in the brain
Our previous study of compounds with neurite regeneration activity found that diosgenin, a compound derived from several species of yam, repaired axonal atrophy and synaptic degeneration and improved memory dysfunction in a the 5XFAD transgenic mouse model of AD [4]
The remaining patients were allocated to a 12-week placebo period and 12-week diosgenin-rich yam extract period with a 6-week interval period, or a 12-week diosgenin-rich yam extract period and 12-week placebo period with a 6-week interval period
Summary
Alzheimer’s disease (AD) is a chronic, progressive, and untreatable neurodegenerative disorder characterized by the accumulation of amyloid β (Aβ) in the brain. Several strategies aimed at reducing Aβ production have long been investigated in basic research and clinical trials centered around the radical development of therapeutic drugs for AD. These approaches have failed to improve cognitive function in phase 2 and 3 trials [2], even when supported by large pharmaceutical companies, and have been withdrawn. Diosgenin-treated mice exhibited increases in axonal density and c-Fos expression in the medial prefrontal and perirhinal cortices, suggesting the enhancement of neuronal network activation. Diosgenin directly binds to and stimulates the membrane-associated rapid response steroid-binding receptor (1,25D3 -MARRS)
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