Bioavailable Concentrations of Delphinidin and Its Metabolite, Gallic Acid, Induce Antioxidant Protection Associated with Increased Intracellular Glutathione in Cultured Endothelial Cells

Abstract

Despite limited bioavailability and rapid degradation, dietary anthocyanins are antioxidants with cardiovascular benefits. This study tested the hypothesis that the antioxidant protection conferred by the anthocyanin, delphinidin, is mediated by modulation of endogenous antioxidant defences, driven by its degradation product, gallic acid. Delphinidin was found to degrade rapidly (t1/2 ~ 30 min), generating gallic acid as a major degradation product. Both delphinidin and gallic acid generated oxygen-centred radicals at high (100 μM) concentrations in vitro. In a cultured human umbilical vein endothelial cell model of oxidative stress, the antioxidant protective effects of both delphinidin and gallic acid displayed a hormesic profile; 100 μM concentrations of both were cytotoxic, but relatively low concentrations (100 nM–1 μM) protected the cells and were associated with increased intracellular glutathione. We conclude that delphinidin is intrinsically unstable and unlikely to confer any direct antioxidant activity in vivo yet it offered antioxidant protection to cells at low concentrations. This paradox might be explained by the ability of the degradation product, gallic acid, to confer benefit. The findings are important in understanding the mode of protection conferred by anthocyanins and reinforce the necessity to conduct in vitro experiments at biologically relevant concentrations.

Dietary Anthocyanins and Stroke: A Review of Pharmacokinetic and Pharmacodynamic Studies

“…On the other hand, it seems that the indirect mechanisms, involving the modulation of cellular signaling pathways and the activity of some transcription factors (Nrf2, NF-kB, Sp1) could be more relevant in vivo. Moreover, recent studies indicated that ACNs’ metabolites, rather than ACN, are responsible for the observed beneficial effects [114,115,116,117,118,119,120]. Also, it is important to underline the fact that only some studies used ACNs or their metabolites at physiologically relevant concentrations [115,116,118,119].…”

Synthesis of novel vanillin derivatives: novel multi-targeted scaffold ligands against Alzheimer's disease

“…Cell survival after treatment with H 2 O 2 (400 μM) was assessed using the MTT cell assay, using a procedure similar to previous publications. 16,46 SH-SY5Y cells were seeded (7000 cells per well) in a 96-well plate. After adhesion (24 h), cells were treated with different concentrations of compound 4, ranging from 0.01 to 5 μM, and incubated for 24 h. Subsequently H 2 O 2 solution was added to the positive control and the test drug wells, followed by incubation for another 24 h. After incubation, all the solutions were removed from all the wells and 100 μL of MTT solution (1 mg mL −1 ) was added in each well.…”

Bioavailability Study of Maqui Berry Extract in Healthy Subjects

“…Besides the interaction with gut microbiota, direct effects of anthocyanin structures or metabolites are additionally described [ 14 , 15 ]. It is becoming clearly recognized that anthocyanins can interact with various molecular targets and affect multiple signalling pathways [ 16 , 17 , 18 , 19 , 20 , 21 ]. To further evaluate the clinical benefits observed with the MBE [ 6 , 7 , 8 , 9 ] it is of high interest to specifically examine the uptake of unmetabolized anthocyanin structures present in the extract.…”