Mechanism of Action and Interactions between Thyroid Peroxidase and Lipoxygenase Inhibitors Derived from Plant Sources

Abstract

This study focused on the effect of kaempferol, catechin, apigenin, sinapinic acid, and extracts from plants (i.e., parsley, cumin, mustard, green tea, and green coffee) on thyroid peroxidase (TPO) and lipoxygenase (LOX) activity, antiradical potential, as well as the result of interactions among them. Catechin, sinapinic acid, and kaempferol acted as a competitive TPO inhibitors, while apigenin demonstrated an uncompetitive mode of inhibitory action. Ethanol extracts from all plants acted as competitive TPO inhibitors, while, after in vitro digestion, TPO activation was found especially in the case of mustard (24%) and cumin (19.85%). Most importantly, TPO activators acted synergistically. The TPO effectors acted as LOX inhibitors. The most effective were potentially bioaccessible compounds from green tea and green coffee (IC50 = 29.73 mg DW/mL and 30.43 mg DW/mL, respectively). The highest free radical scavenging ability was determined for catechin and sinapinic acid (IC50 = 78.37 µg/mL and 84.33 µg/mL, respectively) and potentially bioaccessible compounds from mustard (0.42 mg DW/mL) and green coffee (0.87 mg DW/mL). Green coffee, green tea, cumin, and mustard contain potentially bioaccessible TPO activators that also act as effective LOX inhibitors, which indicate their potentially health-promoting effects for people suffering from Hashimoto’s disease.

Network Pharmacology to Explore the Molecular Mechanisms of Prunella vulgaris for Treating Hashimoto’s Thyroiditis

“…Luteolin is one of the most common flavones with antioxidant, anticancer, antiinflammatory, and antiapoptotic properties in TCMSP (De Stefano et al, 2021). A previous study also suggests that kaempferol is a potential bioaccessible TPO activator based on effective LOX inhibitors, further indicating potentially healthpromoting effects for HT (Habza-Kowalska et al, 2019). Some studies have also shown that luteolin's mechanisms showed potent anti-inflammatory activity, including the activation of NF-κB, which leads to the expression of IL-6 and COX-2 (Xagorari et al, 2001;Ching-Chow et al, 2004).…”

“…In the study, eleven main active components were screened of PV: luteolin, quercetin, beta-sitosterol, kaempferol, stigmasterol, morin, spinasterol, delphinidin, vulgaxanthin-I, poriferasterol monoglucoside_qt, and stigmast-7-enol. Molecular docking showed that the active ingredients, including luteolin and kaempferol, had a good affinity for the hub disease proteins in clinical therapeutics (Xia et al, 2016;Habza-Kowalska et al, 2019). The results demonstrated that luteolin has a strong affinity for disease proteins of HT, and quercetin had a strong affinity for serum thyroid peroxidase (TPO).…”

The Cross-Talk between Polyphenols and the Target Enzymes Related to Oxidative Stress-Induced Thyroid Cancer

“…Sinapinic acid, catechin, and kaempferol were competitive TPO inhibitors, while apigenin was an uncompetitive TPO inhibitor. The highest radical scavengers belonged to sinapinic acid, catechin, and compounds derived from mustard and green coffee [ 93 ].…”

“…Inflammation and oxidative stress are closely connected pathways. Thyroid hormones act as antioxidant balancers, while both hyperthyroidism and hypothyroidism have been determined to be linked with oxidative stress [ 93 , 97 ]. Plants are major sources of antioxidant polyphenols with proven biological effects.…”

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

“…The CI values are presented in Table 5. Our previous studies used this method on pure polyphenolic compounds and plant extracts against TPO and LOX [4,24]. Studies [7] showed the synergistic action of ferulic and chlorogenic acids as LOX inhibitors.…”