Product of pomegranate juice, extract promotes pathway to brain health

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URI researchers identify bioactive compounds that may inhibit Alzheimer’s

KINGSTON, R.I. – March 15, 2016 — Pomegranates and other so-called “superfoods” are known by scientists to have positive effects on the brain – improving functions such as memory and cognition.

But a team of University of Rhode Island researchers has discovered it may not be the superfoods themselves that have positive effects, but rather the way these foodstuffs interact with the body’s microflora during gut microbial metabolism that could lead to breakthroughs in protecting against Alzheimer’s.

Navindra Seeram, an associate professor of biomedical and pharmaceutical science, said his team has found that urolithins, anti-inflammatory and neuroprotective compounds, are created when the body’s gut bacteria breaks down polyphenols, which are present in pomegranate extract. The American Chemical Society recently published a brief account of Seeram’s work in ACS Chemical Neuroscience.

“We knew that a purified pomegranate extract worked in an Alzheimer’s transgenic animal model, and there are a few other groups besides us who have reported similar findings: Pomegranate fruit works,” Seeram said. “But we asked a simple question: What is it within the extract that is really working? And that’s where it became interesting.”

Seeram isolated and identified 21 compounds, mostly polyphenols, from the pomegranate extract but none were able to cross the blood-brain barrier, which protects against unwanted substances from reaching the brain. However, when those polyphenols were biotransformed by the gut microflora, the resulting urolithins were able to cross the barrier.

“We believe that the gut-microbial metabolites were the true active compounds, and not necessarily the natural compounds found in the fruit,” he said. “We isolated all of the constituents, obtained the structures of the compounds and used computational methods to see which ones would likely pass the blood brain barrier.”

While the urolithins have the potential to cross the blood-brain barrier based on the computational studies, Seeram is still unsure whether they actually do and said further in vivo studies would be needed to confirm these initial findings.

Not everyone is able to produce these useful urolithins, however. Each person’s gut microflora is different and, thus, how they metabolize food differs as well. While one person’s body may turn pomegranate extract into urolithins, another person’s gut bacteria may not perform the same function.

Because Seeram was able to identify urolithins as the potentially active compounds for Alzheimer’s, it opens the door to allow researchers to deliver them directly to subjects who cannot produce them naturally.

During the next phase of his research, Seeram and his team will use animal studies to determine if the compounds are actually penetrating the blood-brain barrier, and they will repeat their previous transgenic Alzheimer’s animal experiments using pure urolithins to confirm their findings.

Seeram’s research is exciting to Paula Grammas, director of The George & Anne Ryan Institute for Neuroscience, who recognizes the role the gut microflora can play in protecting and improving cognition and brain function.

“An increasing number of studies suggest that diet and lifestyle has important effects on health in general and specifically on brain health,” she said. “Although much work remains to be done, current data implicate compounds such as urolithins, formed from gut microbial metabolism of pomegranate’s polyphenols, as “neuroprotective”. Investigators at the Ryan Neuroscience Institute will use a broad, multifaceted approach to understanding brain health and plan to explore diet and lifestyle as modifiable risk factors in the prevention of brain diseases such as Alzheimer’s disease.”

Seeram said the hiring of Grammas and the potential hiring of more researchers by the Ryan Neuroscience Institute can be critical to his efforts to understand the neuroprotective effects of urolithins.

“Now that she’s here and hiring a group of researchers with expertise in neuroscience, I am excited about future collaborations with that group to help us move this research forward,” Seeram said. “The Ryan Neuroscience Institute will give us new expertise with new cutting edge techniques and state of the art equipment. This started as a collaboration and it is natural for us to want to extend that.”

Navindra Seeram, associate professor of biomedical and pharmaceutical science at the University of Rhode Island, has isolated and identified 21 compounds from pomegranate juice and extracts that, when they interact with gut microflora inside the human body, can have positive effects on brain cognition and memory. This discovery could lead to breakthroughs in protecting against Alzheimer’s.

Photo courtesy of Navindra Seeram