Effects of Cistanche tubulosa Wight Extract on Locomotive Syndrome: A Placebo-Controlled, Randomized, Double-Blind Study.

In an aging society, preventing dysfunction and restoring function of the locomotive organs are necessary for long-term quality of life. Few interventional studies have investigated supplementation for locomotive syndrome. Additionally, very few interventional clinical studies on locomotive syndrome have been performed as placebo-controlled, randomized, double-blind studies. We previously found that the administration of 30% ethanolic extract of Cistanche tubulosa improved walking ability in a cast-immobilized skeletal muscle atrophy mouse model. Therefore, we conducted a clinical study to evaluate the effects of C. tubulosa (CT) extract on the locomotive syndrome. Twenty-six subjects with pre-symptomatic or mild locomotive syndrome completed all tests and were analyzed in the study. Analyses of muscle mass and physical activity were performed based on the full analysis set. Intake of CT extract for 12 weeks increased step width (two-step test) and gait speed (5 m walking test) in patients over 60 years old compared with those in a placebo control (p = 0.046). In contrast, the skeletal muscle mass of the body trunk and limbs was unchanged following administration of CT extract. Adverse effects were evaluated by blood tests; no obvious adverse events were observed following the intake of CT extract. In conclusion, this placebo-controlled, randomized, double-blind study demonstrated that treatment with CT extract significantly prevented a decline in walking ability without any notable adverse effects in patients with locomotive syndrome.

Diosgenin content is a novel criterion to assess memory enhancement effect of yam extracts.

Several studies have suggested that some kind of Dioscorea species (yam) or yam-contained herbal medicines have cognitive enhancement effect. However, it has been unknown what is a crucial factor for cognitive enhancement in each Dioscorea species. In this study, we aimed to investigate whether one of the main and brain-penetrating components in yams, diosgenin, can be a novel criterion to assess memory enhancement effect of yam extracts. Although our previous studies showed that administration of diosgenin or diosgenin-rich yam extract enhanced cognitive function in normal mice and healthy humans, we have never evaluated whether the effect depends on diosgenin content or not. Therefore, we compared memory enhancement effects of low diosgenin-contained general yam water extract with diosgenin-rich yam extract on cognitive function in normal mice. We found that unlike diosgenin-rich yam, administration of general yam water extract did not enhance object recognition memory in normal mice. LC-MS/MS analyses revealed that after administration of general yam, diosgenin concentration in the brain did not reach to the effective dose because of the low diosgenin content in the original yam extract. On the other hand, when diosgenin was artificially added into general yam, the extract showed memory enhancement in normal mice and promoted neurite outgrowth in neurons. Our study suggests that diosgenin is actually an active compound in yams for memory enhancement, and diosgenin content can be a criterion for predicting cognitive enhancement effect of yam extracts.

Natural Medicines and Their Underlying Mechanisms of Prevention and Recovery from Amyloid Β-Induced Axonal Degeneration in Alzheimer's Disease.

In Alzheimer's disease (AD), amyloid ß (Aß) induces axonal degeneration, neuronal network disruption, and memory impairment. Although many candidate drugs to reduce Aß have been clinically investigated, they failed to recover the memory function in AD patients. Reportedly, Aß deposition occurred before the onset of AD. Once neuronal networks were disrupted by Aß, they could hardly be recovered. Therefore, we speculated that only removal of Aß was not enough for AD therapy, and prevention and recovery from neuronal network disruption were also needed. This review describes the challenges related to the condition of axons for AD therapy. We established novel in vitro models of Aß-induced axonal degeneration. Using these models, we found that several traditional medicines and their constituents prevented or helped recover from Aß-induced axonal degeneration. These drugs also prevented or helped recover from memory impairment in in vivo models of AD. One of these drugs ameliorated memory decline in AD patients in a clinical study. These results indicate that prevention and recovery from axonal degeneration are possible strategies for AD therapy.

Combined Treatment with Two Water Extracts of Eleutherococcus senticosus Leaf and Rhizome of Drynaria fortunei Enhances Cognitive Function: A Placebo-Controlled, Randomized, Double-Blind Study in Healthy Adults.

We previously found that the water extract of Eleutherococcus senticosus leaves (ES extract) enhanced cognitive function in normal mice. Our study also revealed that the water extract of rhizomes of Drynaria fortunei (DR extract) enhanced memory function in Alzheimer's disease model mice. In addition, our previous experiments suggested that a combined treatment of ES and DR extracts synergistically improved memory and anti-stress response in mice. Although those two botanical extracts are expected to be beneficial for neuropsychological function, no clinical data has ever been reported. Therefore, we performed a placebo-controlled, randomized, double-blind study to evaluate cognitive enhancement and anti-stress effects by the intake of a combined extract in healthy volunteers. The intake period was 12 weeks. The Japanese version of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) test was used for neurocognitive assessment. The combined treatment of ES and DR extracts significantly increased the figure recall subscore of RBANS (p = 0.045) in an intergroup comparison. Potentiation of language domain ((p = 0.040), semantic fluency (p = 0.021) and figure recall (p = 0.052) was shown by the extracts (in intragroup comparison). In anti-stress response, the anxiety/uncertainly score was improved by the extract in an intragroup comparison (p = 0.022). No adverse effects were observed. The combined treatment of ES and DR extracts appear to safely enhance a part of cognitive function in healthy adults.

Memory Enhancement by Oral Administration of Extract of Eleutherococcus senticosus Leaves and Active Compounds Transferred in the Brain.

The pharmacological properties of Eleutherococcus senticosus leaf have not been clarified although it is taken as a food item. In this study, the effects of water extract of Eleutherococcus senticosus leaves on memory function were investigated in normal mice. Oral administration of the extract for 17 days significantly enhanced object recognition memory. Compounds absorbed in blood and the brain after oral administration of the leaf extract were detected by LC-MS/MS analyses. Primarily detected compounds in plasma and the cerebral cortex were ciwujianoside C3, eleutheroside M, ciwujianoside B, and ciwujianoside A1. Pure compounds except for ciwujianoside A1 were administered orally for 17 days to normal mice. Ciwujianoside C3, eleutheroside M, and ciwujianoside B significantly enhanced object recognition memory. These results demonstrated that oral administration of the leaf extract of E. senticosus enhances memory function, and that active ingredients in the extract, such as ciwujianoside C3, eleutheroside M, and ciwujianoside B, were able to penetrate and work in the brain. Those three compounds as well as the leaf extract had dendrite extension activity against primary cultured cortical neurons. The effect might relate to memory enhancement.

Diosgenin-Rich Yam Extract Enhances Cognitive Function: A Placebo-Controlled, Randomized, Double-Blind, Crossover Study of Healthy Adults.

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.