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

Abstract

Hundreds of millions of people around the globe are afflicted by diabetes mellitus. The alteration in glucose fixation process might result into hyperglycaemia and could affect the circulating plasma proteins to undergo nonenzymatic glycation reaction. If it is unchecked, it may lead to diabetes with increase in advanced glycation end products (AGEs). Therefore, the present study was designed to inhibit the diabetes and glycation by using natural antioxidant “ellagic acid” (EA). In this study, we explored the antidiabetes and antiglycation potential of EA in both in vitro (EA at micromolar concentration) and in vivo systems. The EA concentrations of 10 and 20 mg kg-1B.W./day were administered orally for 25 days to alloxan-induced diabetic rats, a week after confirmation of stable diabetes in animals. Intriguingly, EA supplementation in diabetic rats reversed the increase in fasting blood sugar (FBS) and hemoglobin A1c (HbA1c) level. EA also showed an inhibitory role against glycation intermediates including dicarbonyls, as well as AGEs, investigated in a glycation mixture with in vitro and in vivo animal plasma samples. Additionally, EA treatment resulted in inhibition of lipid peroxidation-mediated malondialdehyde (MDA) and conjugated dienes (CD). Furthermore, EA exhibited an antioxidant property, increased the level of plasma glutathione (GSH), and also helped to decrease histological changes evaluated by histoimmunostaining of animal kidney tissues. The results from our investigation clearly indicates the antiglycative property of EA, suggesting EA as an adequate inhibitor of glycation and diabetes, which can be investigated further in preclinical settings for the treatment and management of diabetes-associated complications.

Biological investigations on macro-morphological characteristics, polyphenolic acids, antioxidant activity of Perilla frutescens (L) Britt. grown under open field

“…It may be found in free form or as complex compounds (ellagitannins), which can be converted to ellagic acid and its metabolites, such as urolithins ( Rios et al, 2018 ). Ellagic Acid has been shown to have antioxidants ( Zeb and Akbar, 2018 , Tošović and Bren, 2020 ), osteoarthritis ( Lin et al, 2020a , Lin et al, 2020b ), diabetes ( Ahmad, 2022 ), anti-inflammatory ( Cornélio et al, 2013 ), antiplatelet activity ( Chang, 2013 ), Neuroprotective ( He at al., 2020 ). Kang and Lee (2011) , found three different phenolic acids from purple perilla which were caffeic acid, rosmarinic acid, and rosmarinic acid methylester.…”

Antiglycation potential of plant based TiO2 nanoparticle in D‐ribose glycated BSA in vitro

“…The glycated protein BSA were prepared as per the protocol for glycation previously performed with very slight modification. 23 The BSA (1 mg ml −1 ) with 25 mM D-ribose were dissolved in 10 mM phosphate buffer saline (PBS) at pH 7.4 with and without addition of TNP and AG (standard drug) and were incubated at 37°C for around 20 days under sterile conditions. 9 For antiglycation purpose, we used different concentrations including 100 and 200 μM, for both TNP and AG.…”

Nonenzymatic glycosylation of isolated human immunoglobulin‐G by D‐ribose

“…The susceptible nucleophilic amino group involved in reversible condensation with a carbonyl group of the reducing sugar is the possible mechanism that contributes to elevating the formation of unstable Schiff's base, an intermediate of the glycation process, which can further undergo a spontaneous multistep rearrangement and acid‐base reactions to form unstable Amadori products 8–11 . The intermediate Amadori products may further undergo rearrangements, dehydrations, and cyclizations to form highly stable advanced glycation end products (AGEs) 12–15 . The formation of heterogeneous AGEs is slow and continuous, but the hyperglycemic condition can cause a multi‐fold increase in AGEs such as carboxyethyllysine (CEL), pentosidine, and carboxymethyllysine (CML) 16–18 …”

“…[8][9][10][11] The intermediate Amadori products may further undergo rearrangements, dehydrations, and cyclizations to form highly stable advanced glycation end products (AGEs). [12][13][14][15] The formation of heterogeneous AGEs is slow and continuous, but the hyperglycemic condition can cause a multi-fold increase in AGEs such as carboxyethyllysine (CEL), pentosidine, and carboxymethyllysine (CML). [16][17][18] D-ribose is a naturally occurring, aldofuranose portraying five-membered ring sugar and is known to be vulnerable to reacting with an amino group of proteins present in all living cells and is also associated with cellular metabolism.…”