Pomegranate's Neuroprotective Effects against Alzheimer's Disease Are Mediated by Urolithins, Its Ellagitannin-Gut Microbial Derived Metabolites
Date of Original Version
Pomegranate shows neuroprotective effects against Alzheimer's disease (AD) in several reported animal studies. However, whether its constituent ellagitannins and/or their physiologically relevant gut microbiota-derived metabolites, namely, urolithins (6H-dibenzo[b,d]pyran-6-one derivatives), are the responsible bioactive constituents is unknown. Therefore, from a pomegranate extract (PE), previously reported by our group to have anti-AD effects in vivo, 21 constituents, which were primarily ellagitannins, were isolated and identified (by HPLC, NMR, and HRESIMS). In silico computational studies, used to predict blood-brain barrier permeability, revealed that none of the PE constituents, but the urolithins, fulfilled criteria required for penetration. Urolithins prevented β-amyloid fibrillation in vitro and methyl-urolithin B (3-methoxy-6H-dibenzo[b,d]pyran-6-one), but not PE or its predominant ellagitannins, had a protective effect in Caenorhabditis elegans post induction of amyloid β1-42 induced neurotoxicity and paralysis. Therefore, urolithins are the possible brain absorbable compounds which contribute to pomegranate's anti-AD effects warranting further in vivo studies on these compounds. (Figure Presented).
Publication Title, e.g., Journal
ACS Chemical Neuroscience
Yuan, Tao, Hang Ma, Weixi Liu, Daniel B. Niesen, Nishan Shah, Rebecca Crews, Kenneth N. Rose, Dhiraj A. Vattem, and Navindra P. Seeram. "Pomegranate's Neuroprotective Effects against Alzheimer's Disease Are Mediated by Urolithins, Its Ellagitannin-Gut Microbial Derived Metabolites." ACS Chemical Neuroscience 7, 1 (2016): 26-33. doi: 10.1021/acschemneuro.5b00260.