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

• Main Authors: Ewa Habza-Kowalska, Agnieszka A. Kaczor, Damian Bartuzi, Jacek Piłat, Urszula Gawlik-Dziki
• Format: Article
• Language: English
• Published: MDPI AG 2021-05-01
• Series: International Journal of Molecular Sciences
• Subjects: thyroid peroxidase (TPO); lipoxygenase (LOX); inhibition; dietary polyphenols; antioxidant activity; interactions
• Online Access: https://www.mdpi.com/1422-0067/22/10/5108

The presented research concerns the triple activity of <i>trans</i>-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.