Alzheimer’s Neuroprotective Agent in Pomegranate Extract Possibly Identified

Researchers have identified urolithins are the molecules responsible for pomegranate extract’s apparent neuroprotective effectives against Alzheimer’s disease. The study, entitled “Pomegranate’s Neuroprotective Effects against Alzheimer’s Disease Are Mediated by Urolithins, Its Ellagitannin-Gut Microbial Derived Metabolites,” was published in ACS Chemical Neuroscience.

Several animal studies have demonstrated that pomegranate has neuroprotective effects against Alzheimer’s disease (AD). However, until now, researchers couldn’t quite pinpoint which bioactive compounds in the fruit were responsible for this protective effect. Dr. Navindra P. Seeram and colleagues previously reported that a pomegranate extract (PE), rich in antioxidant micronutrients polyphenols, had anti-AD properties in an animal model. Now, the team has identified the exact compounds responsible for this effect.

One of the hallmarks of Alzheimer’s disease pathogenesis is the accumulation of the amyloid beta protein in plaques that lead to neurodegeneration. To protect the brain against these structures and prevent their formation, compounds have to be able to cross the blood-brain barrier, a highly selective membrane that separates the circulating blood from the brain.

In this study, researchers identified and isolated 21 compounds, mostly ellagitannins, a type of polyphenol. Using computational studies, they predicted which of these compounds would be able to cross the blood-brain barrier. According to the computational permeability prediction, of the 21 constituents, only urolithins, the product of ellagitannins’ metabolization by the gut microflora, would be able to penetrate the barrier. These compounds were also able to prevent β-amyloid fibrillation in vitro. Furthermore, methyl-urolithin B had a protective effect against neurotoxicity and paralysis in vivo and increased the lifespan of an Alzheimer’s disease worm model, Caenorhabditis elegans. 

“Urolithins are the possible brain absorbable compounds which contribute to pomegranate’s anti-AD effects, warranting further in vivo studies on these compounds,” researchers concluded.