Some Dietary Phenolic Compounds Can Activate Thyroid Peroxidase and Inhibit Lipoxygenase-Preliminary Study in the Model Systems

The presented research concerns the triple activity of trans-cinnamic (tCA), ferulic (FA) and syringic acids (SA). They act as thyroid peroxidase (TPO) activators, lipoxygenase (LOX) inhibitors and show antiradical activity. All compounds showed a dose-dependent TPO activatory effect, thus the AC50...

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Bibliographic Details
Published in:International journal of molecular sciences 2021-05, Vol.22 (10), p.5108
Main Authors: Habza-Kowalska, Ewa, Kaczor, Agnieszka A., Bartuzi, Damian, Piłat, Jacek, Gawlik-Dziki, Urszula
Format: Article
Language:English
Subjects:
Allosteric properties
Antagonism
antioxidant activity
Antioxidants
Binding sites
Cereals
dietary polyphenols
Disease
Enzymes
Fruits
Hypothyroidism
Inflammation
inhibition
Inhibitors
interactions
Iodide peroxidase
Lipoxygenase
lipoxygenase (LOX)
Liquid oxygen
Metabolites
Oxidative stress
Peroxidase
Phenolic compounds
Phenols
Polyphenols
Thyroid
Thyroid gland
thyroid peroxidase (TPO)
Vegetable oils
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Summary:The presented research concerns the triple activity of trans-cinnamic (tCA), ferulic (FA) and syringic acids (SA). They act as thyroid peroxidase (TPO) activators, lipoxygenase (LOX) inhibitors and show antiradical activity. All compounds showed a dose-dependent TPO activatory effect, thus the AC50 value (the concentration resulting in 50% activation) was determined. The tested compounds can be ranked as follows: tCA > FA > SA with AC50 = 0.10, 0.39, 0.69 mM, respectively. Strong synergism was found between FA and SA. The activatory effects of all tested compounds may result from interaction with the TPO allosteric site. It was proposed that conformational change resulting from activator binding to TPO allosteric pocket results from the flexibility of a nearby loop formed by residues Val352-Tyr363. All compounds act as uncompetitive LOX inhibitors. The most effective were tCA and SA, whereas the weakest was FA (IC50 = 0.009 mM and IC50 0.027 mM, respectively). In all cases, an interaction between the inhibitors carboxylic groups and side-chain atoms of Arg102 and Arg139 in an allosteric pocket of LOX was suggested. FA/tCA and FA/SA acted synergistically, whereas tCA/SA demonstrated antagonism. The highest antiradical activity was found in the case of SA (IC50 = 0.22 mM). FA/tCA and tCA/SA acted synergistically, whereas antagonism was found for the SA/FA mixture.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22105108