Preventive Effect of Dementia on the Extract of Alpinia Galanga (P14-016-19)

Abstract

Objectives

The number of dementia is rapidly increased in world wide. The most frequent ratio among these is Alzheimer's disease (AD) and second one is Frontotemporal dementia (FD). It is known that amyloid β and tau proteins accumulates in the brain of these dementia. These proteins form oligomers in the brain and inhibit the functions of neurons. Therefore, it has been highly desirable to find a method of preventing and treating dementia. 1′-Acetoxychavicol acetate (ACA), which is naturally obtained from the rhizomes of Alpinia galanga has various biological properties. We have already reported that ACA ameliorates age-related spatial memory deterioration by increasing serum ketone body production as a complementary energy source for neuronal cells of senescence-accelerated mice prone 8 (SAMP8) mice. However, SAMP8 is not necessarily suitable for in vivo dementia model. Recently, new human dementia model was developed. APP_OSK mice is a useful model of AD. Tau784 mice is a useful model of FD. Here, we examined to clarify the preventive effect of the extract of Alpinia galanga (EAG) on dementia using APP_OSK mice and Tau784 mice.

Methods

APP_OSK and its homologous control (Non-Tg) mice (13 months of age), Tau784 and its homologous control (Non-Tg) mice (15 months of age) were used. 0.017% EAG or dH₂O was administered intragastrically every day for 2 months. Morris water maze was tested to monitor spatial memory. Serum β-hydroxybutyric acid level was measured. The expressions of amyloid β, Tau phosphorylation, neuronal nuclei, and synaptophysin were measured by immnohistochemical analysis.

Results

The cognitive function of APP_OSK and Tau784 mice was markedly lower than that of each homologous control mice, but was improved by administering EAG. The expressions of amyloid β and Tau phosphorylation in the brain did not change with/without EAG. On the other hand, the serum β-hydroxybutyric acid level was significantly increased by the administration of EAG. EAG showed a tendency to increase the expression of synaptophysin, a marker of synapse. Furthermore, the neuronal nuclei positive cell size in entorhinal cortex of Tau784 mice was significantly increased by the administration of EAG.

Conclusions

These findings confirm that extract of Alpinia galanga improves cognitive function in human AD and FD model mice.

Funding Sources

This study was supported by JSPS KAKENHI Grant Numbers JP24500987, JP15K00832.