OMU Finds that Chinese herbal medicine and tea materials improve cognitive function in mice

A research group led by Professor Takami Tomiyama of the Department of Translational Neuroscience, Osaka Metropolitan University Graduate School of Medicine, in collaboration with Cerebro Pharma, which is a university venture company, Teijin Limited, and other institutions, has discovered that Mamaki leaves used to make herbal tea and Acorus tatarinowii/gramineus and Zizyphi spinosi semen used in traditional Chinese medicine, have effects of preventing dementia and rejuvenating the brain. The findings are expected to contribute to the development of dementia-preventive foods. The results related to Mamaki leaves, Acorus tatarinowii/gramineus, and Zizyphi spinosi semen were published in GeroScience, Nutrients, and eLife, respectively.

Dementia is thought to be caused by degeneration of neurons due to the accumulation of abnormal proteins, such as amyloid beta (Aβ), tau, and α-synuclein, in the brain. However, once the neurons are dead, removing abnormal proteins is no longer effective, and prevention must begin while the neurons are healthy. Since dementia prevention continues over a long period, it should use substances that are safe, inexpensive, effective against various causative proteins, and capable of repairing damaged neurons. Moreover, it is also desirable that middle-aged and elderly people can purchase and take them at their discretion. Nevertheless, it is difficult to meet all these conditions with a drug containing a single active pharmaceutical ingredient.

The research group thought that foods containing various ingredients could satisfy these conditions and decelerate aging. Thus, they explored natural ingredients such as Oriental herbal medicines and Western herbs to find promising ones for dementia prevention. They focused on Zizyphi spinosi semen (seeds of Ziziphus jujuba Miller var. spinosa) and leaves (rhizomes are usually used, but the leaves were used in the study) of Acorus tatarinowii/gramineus, which are used in traditional Chinese medicine, and Mamaki leaves used to make Hawaiian herbal tea.

The group administered hot water extracts of Zizyphi spinosi semen and Acorus tatarinowii/gramineus leaves to mouse models of Alzheimer's disease, frontotemporal dementia, and Parkinson's disease/dementia with Lewy bodies and found that brain Aβ, tau, and α-synuclein pathologies improved and cognitive and motor functions were restored. Hot water extract of Mamaki leaves also improved brain pathologies and restored cognitive function in various mouse models of dementia.

To increase the potency, they prepared simple crushed powder without undergoing hot water extraction and examined its medicinal effects in the mouse models. The results showed that the simple crush powder preparation of Zizyphi spinosi semen had stronger effects of improving brain pathologies and cognitive function than the extract preparation. The simple crush powder preparation improved cognitive function to same level or higher than that of normal mice. It was also found that the hot water extraction residue had residual activity, which was equivalent to the extract activity.

The strong effects of simple crush powder suggest that some active components cannot be recovered or are lost by hot water extraction. Furthermore, simple crush powder preparations of Acorus tatarinowii leaves and Mamaki leaves were also shown to have stronger effects than the corresponding extract preparations.

Simple crush powder of Mamaki fruits had even stronger effects than Mamaki leaves. Model mice receiving the fruit powder preparation showed higher cognitive function levels than normal mice. The cognitive function restoration by simple crush powder of Zizyphi spinosi semen in model mice to levels above those of normal mice suggests that this dietary material may not only eliminate brain pathology but also directly improve brain function. Therefore, they fed this sample to normal elderly mice for 1 month and compared the levels of cognitive function and cellular senescence in these mice with those in young mice.

The results showed that the simple crushed powder sample reduced cellular senescence in aged mice and improved cognitive function to the same level as in young mice. Moreover, the simple crushed powder preparation also increased the expression of brain-derived neurotrophic factor, which is necessary to repair damaged neurons, and promoted neurogenesis. These results indicate that the simple crushed powder preparation of Zizyphi spinosi semen has effects of preventing dementia and rejuvenating the brain. Moving forward, the research group intends to elucidate the effects of these dietary materials on intestinal bacteria and other indicators of aging and the mechanisms underlying these effects. They will also identify the active ingredients.

Tomiyama said, "This study was conducted by a research group comprising mainly researchers of a university venture based on the results of research at the university. The dietary materials developed in this study not only prevent dementia but also decelerate brain aging. With these foods, we aim for a society with zero dementia."

Journal Information
Publication: GeroScience
Title: Hawaiian native herb Mamaki prevents dementia by ameliorating neuropathology and repairing neurons in four different mouse models of neurodegenerative diseases
DOI: 10.1007/s11357-023-00950-y

Publication: Nutrients
Title: New Value of Acorus tatarinowii/gramineus Leaves as a Dietary Source for Dementia Prevention
DOI: 10.3390/nu16111589

Publication: eLife
Title: Simply crushed Zizyphi spinosi semen prevents neurodegenerative diseases and reverses age-related cognitive decline in mice
DOI: 10.7554/eLife.100737.1