Excessive concentrations of vascular endothelial growth factor (VEGF) trigger angiogenesis, which causes complications such as the destabilization of atherosclerotic plaques and increased growth of tumors. This work focuses on the determination of the inhibitory activity of melatonin and other indolic related compounds on VEGF-induced VEGF receptor-2 (VEGFR-2) activation and an approximation to the molecular mechanism underlying the inhibition. Quantification of phosphorylated VEGFR-2 was measured by ELISA. Migration wound-healing assay was used to determine cell migration of human umbilical vein endothelial cells (HUVECs). This is the first time that melatonin, 3-indolacetic acid, 5-hydroxytryptophol, and serotonin are proved to significantly inhibit VEGF-induced VEGFR-2 activation in human umbilical vein endothelial cells and subsequent angiogenesis. 3-Indolacetic acid showed the highest inhibitory effect (IC50 value of 0.9704 mM), followed by 5-hydroxytryptophol (35% of inhibition at 0.1 mM), melatonin (30% of inhibition at 1 mM), and serotonin (24% of inhibition at 1 mM). An approximation to the molecular mechanism of the inhibition has been proposed, suggesting that indolic compounds might interact with the cell surface components of the endothelial membrane in a way that prevents VEGF from activating the receptor. Additionally, wound-healing assay revealed that exposure of HUVECs to melatonin and 3-indolacetic acid in the presence of VEGF significantly inhibited cell migration by 87% and 99%, respectively, after 24 h. These data demonstrate that melatonin, 3-indolacetic acid, 5-hydroxytryptophol, and serotonin would be good molecules for future exploitation as anti-VEGF signaling agents.
Protocatechuic acid (PCA) is the major metabolite of the anthocyanin known as cyanidin 3-glucoside. It is found in plasma and tissues, such as the brain, heart, liver, and kidneys, following consumption of a rich source of this flavonoid. The abnormal pathological assembly of amyloid-β (Aβ) and α-synuclein (αS) is an underlying mechanism involved in the formation of amyloid plaques and Lewy bodies in the brain, which are responsible for neuropathology symptoms in Alzheimer's (AD) and Parkinson's diseases (PD), respectively. This research was performed to evaluate the protective effects of PCA, by establishing its potential role in inhibiting aggregation and fibril destabilization of Aβ and αS proteins. It has been found that PCA inhibits the aggregation of Aβ and αS and destabilizes their preformed fibrils. These results were confirmed by TEM images, electrophoresis, and immunoblotting experiments. Furthermore, PCA prevents the death of PC12 cells triggered by Aβ- and αS-induced toxicity.
Anthocyanins are the major polyphenolic compounds in strawberry fruit responsible for its color. Due to their sensitivity, they are affected by food processing techniques such as fermentation that alters both their chemical composition and organoleptic properties. This work aims to evaluate the impact of different fermentation processes on individual anthocyanins compounds in strawberry wine and vinegar by UHPLC-MS/MS Q Exactive analysis. Nineteen, 18, and 14 anthocyanin compounds were identified in the strawberry initial substrate, strawberry wine, and strawberry vinegar, respectively. Four and 8 anthocyanin compounds were tentatively identified with high accuracy for the 1st time to be present in the beverages obtained by alcoholic fermentation and acetic fermentation of strawberry, respectively. Both, the total and the individual anthocyanin concentrations were decreased by both fermentation processes, affecting the alcoholic fermentation to a lesser extent (19%) than the acetic fermentation (91%). Indeed, several changes in color parameters have been assessed. The color of the wine and the vinegar made from strawberry changed during the fermentation process, varying from red to orange color, this fact is directly correlated with the decrease of anthocyanins compounds.
In this study, the nonanthocyanin (poly)phenolic profile of an alcoholic-fermented strawberry beverage was characterized. High-performance liquid chromatography coupled with a triple-quadropole mass spectrometer and ultra-high-performance liquid chromatography coupled with a linear trap quadropole and an Orbitrap mass analyzer was used to identify nonanthocyanin phenolic compounds. Sixty-six compounds were identified, and 13 of these were identified for the first time in strawberry or its derived alcoholic fermented beverage: protocatechuic acid-4-O-β-hexoside, brevifolin carboxylic acid, ferulic acid glucuronide, dimer caffeic acid-O-hexoside, luteolin-3'-O-xyloside, isorhamnetin 3-O-glucoside, taxifolin-O-glucoside, (+)-aromadendrin rhamnoside, eriodictyol-7-O-glucoside, (+)-taxifolin, (+)-aromadendrin, eriodictyol, and homovanillic acid. The alcoholic fermentation process produced significant increases in certain compounds, such as homovanillic acid and p-hydroxybenzoic acid, while a significant decrease in galloyl bis-HHDP-glucose was observed. Linear discriminant analysis correctly classified samples initial, final, and pasteurized, which led to the conclusion that alcoholic fermentation induces significant changes in composition, mainly in relation to the 19 compounds represented in the tables of this work.
Tryptophan, phenylalanine, and tyrosine play an important role as nitrogen sources in yeast metabolism. They regulate biomass production and fermentation rate, and their catabolites contribute to wine health benefits and sensorial character through the yeast biotransformation of grape juice constitutes into biologically active and flavor-impacting components. A UHPLC-MS/MS method was applied to monitor 37 tryptophan/phenylalanine/tyrosine yeast metabolites both in extra-and intracellular extracts produced by the fermentation of two Saccharomyces cerevisiae strains and one Torulaspora delbrueckii. The results shed light on the intra-and extra-cellular metabolomic dynamics, by combining metabolic needs, stimuli, and signals. Among others, the results indicated (a) the production of 2-aminoacetophenone by yeasts, mainly by the two Saccharomyces cerevisiae; (b) the deactivation and/or detoxification of tryptophol via sulfonation reaction; and (c) the deacetylation of N-acetyl tryptophan ethyl ester and N-acetyl tyrosine ethyl ester by producing the corresponding ethyl esters.
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