REVIEW | doi:10.20944/preprints202004.0100.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: ellagic acid; oral administration; bioavailability; microformulations; nanoformulations; solubility enhancement
Online: 7 April 2020 (12:02:54 CEST)
Ellagic acid, a polyphenolic compound present in fruits and berries, has recently been object of extensive research for its antioxidant activity, which might be useful for the prevention and treatment of cancer, cardiovascular pathologies, and neurodegenerative disorders. Its protective role justifies numerous attempts to include it in functional food preparations and in dietary supplements not only to limit the unpleasant collateral effects of chemotherapy. However, ellagic acid use as chemopreventive agent has been debated because of its poor bioavailability associated to low solubility, limited permeability, first pass effect, and interindividual variability in gut microbial transformations. To overcome these drawbacks, various strategies for oral administration including solid dispersions, micro-nanoparticles, inclusion complexes, self-emulsifying systems, polymorphs have been proposed. Here, we have listed an updated description of pursued micro/nanotechnological approaches focusing on the fabrication processes and the features of the obtained products, as well as on the positive results yielded by in vitro and in vivo studies in comparison to the raw material. The micro/nano-sized formulations here described might be exploited for pharmaceutical delivery of this active, as well as for the production of nutritional supplements or for the enrichment of novel foods.
Subject: Chemistry, Food Chemistry Keywords: pomegranate tannins; ellagic acid; molecular modelling; α2-adrenoreceptors; α2-ARs; molecular dynamic simulations; antioxidant; natural compounds; antidepressant activity; food chemistry
Online: 1 October 2021 (14:27:20 CEST)
Polyphenol ellagic acid (EA) possesses anti-oxidant, anti-inflammatory, anti-carcinogenic, anti-diabetic and cardio protection activities, remarking it an interesting multi-targeting profile. EA also controls the central nervous system (CNS) since it was proven to reduce the immobility time of mice in both the forced swimming and the tail-suspension tests, with an efficiency comparable to that of classic antidepressants. Interestingly, the anti-depressant-like effect was almost nulled by the concomitant administration of selective antagonists of the noradrenergic receptors, suggesting the involvement of these cellular targets in the central effects elicited by EA and its derivatives. By in silico and in vitro studies, we discuss how EA engages with human α2A-ARs and α2C-AR catalytic pockets, comparing EA behaviour with those ones of known agonist and antagonist. Structurally, the hydrophobic residues surrounding α2A-AR pocket confer specificity on the intermolecular interactions and hence lead to favourable binding of EA in the α2A-AR, with respect to α2C-AR. Moreover, EA seems to better accommodate within α2A-ARs into TM5 area, closely to S200 and S204 which play a crucial role for activation of aminergic GPCRs such as the α2-AR, highlighting its promising role as a partial agonist. Consistently, EA mimics clonidine in inhibiting noradrenaline exocytosis from hippocampal nerve endings in an yohimbine-sensitive fashion that confirms the engagement of naïve α2-ARs in the EA-mediated effect.