Ellagic Acid as a Tool to Limit the Diabetes Burden: Updated Evidence

Abstract

Oxidative stress contributes not only to the pathogenesis of type 2 diabetes (T2D) but also to diabetic vascular complications. It follows that antioxidants might contribute to limiting the diabetes burden. In this review we focus on ellagic acid (EA), a compound that can be obtained upon intestinal hydrolysis of dietary ellagitannins, a family of polyphenols naturally found in several fruits and seeds. There is increasing research on cardiometabolic effects of ellagitannins, EA, and urolithins (EA metabolites). We updated research conducted on these compounds and (I) glucose metabolism; (II) inflammation, oxidation, and glycation; and (III) diabetic complications. We included studies testing EA in isolation, extracts or preparations enriched in EA, or EA-rich foods (mostly pomegranate juice). Animal research on the topic, entirely conducted in murine models, mostly reported glucose-lowering, antioxidant, anti-inflammatory, and anti-glycation effects, along with prevention of micro- and macrovascular diabetic complications. Clinical research is incipient and mostly involved non-randomized and low-powered studies, which confirmed the antioxidant and anti-inflammatory properties of EA-rich foods, but without conclusive results on glucose control. Overall, EA-related compounds might be potential agents to limit the diabetes burden, but well-designed human randomized controlled trials are needed to fill the existing gap between experimental and clinical research.

Avens Root (Geum Urbanum L.) Extract Discovered by Target-Based Screening Exhibits Antidiabetic Activity in the Hen’s Egg Test Model and Drosophila melanogaster

“…This is in line with previous studies on G. urbanum extracts ( Owczarek et al, 2015 ; Granica et al, 2016 ; Neshati et al, 2018 ; Al-Snafi, 2019 ). In particular, ellagic acid and its derivatives have been suggested to be very promising agents against DM and diabetic complications as recently summarized ( Amor et al, 2020 ). Some effects reported herein are of great interest in the context of our study: First, a α-glucosidase inhibition by ellagic acid-rich plant extracts is described which is far more effective than the inhibition of α-amylase ( Kam et al, 2013 ; Yin et al, 2014 ; Bellesia et al, 2015 ).…”

Subclinical hypothyroidism contributes to poor glycemic control in patients with type 2 diabetes mellitus, and ellagic acid attenuates methimazole‐induced abnormal glucose metabolism in mice model

“…In randomized controlled trial and murine models, EA exhibits a favorable performance to improve blood glucose and diabetes‐related complications (Amor & Gómez‐Guerrero, 2020; Ghadimi et al., 2021). In T2DM patients, blood sugar and hemoglobin A1c are significantly downregulated in response to EA administration (Ghadimi et al., 2021).…”

Physicochemical Characterization of In Vitro LDL Glycation and Its Inhibition by Ellagic Acid (EA): An In Vivo Approach to Inhibit Diabetes in Experimental Animals

“…Our results of CML inhibition by EA are correlated with the study in which EA inhibited the accumulation of CML in the diabetic kidney [ 61 ]. The antiglycation studies of EA suggested that EA could protect the proteins to some extent against the formation of AGEs induced by glycation as evident by the progressive decrease in AGEs with increasing EA concentration [ 51 , 62 ].…”