Pomegranate's Neuroprotective Effects against Alzheimer's Disease Are Mediated by Urolithins, Its Ellagitannin-Gut Microbial Derived Metabolites

Authors

Tao Yuan, University of Rhode Island
Hang Ma, University of Rhode Island
Weixi Liu, University of Rhode Island
Daniel B. Niesen, University of Rhode Island
Nishan Shah, University of Rhode Island
Rebecca Crews, Texas State University
Kenneth N. Rose, University of Rhode Island
Dhiraj A. Vattem, Texas State University
Navindra P. Seeram, University of Rhode Island

Document Type

Article

Date of Original Version

1-20-2016

Abstract

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

Volume

7

Issue

1

Citation/Publisher Attribution

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.