Fisetin Effectively Prevents Age-Related Dementias in Model

Neurodegenerative disease researchers used a rapidly aging mouse model to study the effect of the natural plant compound fisetin on the development of Alzheimer's disease (AD) and other forms of dementia.

Investigators at the Salk Institute for Biological Studies (La Jolla, CA, USA) had shown previously that the antioxidant fisetin could help treat age-related mental decline and conditions such as hereditary familial AD, which accounts for about 1 to 3% of cases of Alzheimer's, or stroke. However, the possible use of fisetin to treat age-related dementias such as sporadic AD had not been examined.

In the current study, the investigators hypothesized that fisetin would be effective against brain aging and cognitive dysfunction in rapidly aging senescence-accelerated prone 8 (SAMP8) mice, a model for sporadic AD and dementia. To test this theory, they fed prematurely aging SAMP8 mice a daily dose of fisetin with their food from the age of three months until the age of 10 months. A control group of SAMP8 mice was fed the same food without fisetin. During the study period, mice were subjected to activity and memory tests. Levels of specific proteins related to brain function, responses to stress, and inflammation were determined.

Results published in the June 2, 2017, online edition of the Journals of Gerontology Series A revealed that fisetin reduced cognitive deficits in old SAMP8 mice while restoring multiple markers associated with impaired synaptic function, stress, and inflammation.

"At 10 months, the differences between these two groups were striking," said senior author Dr. Pamela Maher, a senior researcher at the Salk Institute for Biological Studies. "Mice not treated with fisetin had difficulties with all the cognitive tests as well as elevated markers of stress and inflammation. Brain cells called astrocytes and microglia, which are normally anti-inflammatory, were now driving rampant inflammation. Mice treated with fisetin, on the other hand, were not noticeably different in behavior, cognitive ability or inflammatory markers at 10 months than a group of untreated three-month-old mice with the same condition. Additionally, the team found no evidence of acute toxicity in the fisetin-treated mice, even at high doses of the compound. Mice are not people, of course, but there are enough similarities that we think fisetin warrants a closer look, not only for potentially treating sporadic AD but also for reducing some of the cognitive effects associated with aging, generally."

"Companies have put fisetin into various health products but there has not been enough serious testing of the compound," said Dr. Maher. "Based on our ongoing work, we think fisetin might be helpful as a preventative for many age-associated neurodegenerative diseases, not just Alzheimer's, and we would like to encourage more rigorous study of it."

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Salk Institute for Biological Studies