Toll-like Receptors as a Target of Food-derived Anti-inflammatory Compounds

• DOI: 10.1074/jbc.m114.585901
• Publication Date: 2014-10-08T00:31:17Z
• Authors: Takahiro Shibata; Fumie Nakashima; Kazuya Honda; Yu-Jhang Lu; Tatsuhiko Kondo; Yusuke Ushida; Koichi Aizawa; Hiroyuki Suganuma; Sho Oe; Hiroshi Tanaka; Takashi Takahashi; Koji Uchida
• Keywords: Fluorescein isothiocyanate

Toll-like receptors (TLRs) play a key role in linking pathogen recognition with the induction of innate immunity. They have been implicated pathogenesis chronic inflammatory diseases, representing potential targets for prevention/treatment. Vegetable-rich diets are associated reduced risk several disorders. In present study, based on an extensive screening vegetable extracts TLR-inhibiting activity HEK293 cells co-expressing TLR NF-κB reporter gene, we found cabbage and onion to be richest sources signaling inhibitor. To identify active substances, performed activity-guiding separation principal inhibitors identified 3-methylsulfinylpropyl isothiocyanate (iberin) from quercetin 4'-O-β-glucoside onion, among which iberin showed most potent inhibitory effect. It was revealed that specifically acted dimerization step TLRs pathway. gain insight into mechanism dimerization, developed novel probe combining isothiocyanate-reactive group alkyne functionality click chemistry detected bound living cells, suggesting disrupts via covalent binding. Furthermore, designed variety analogues inhibition potency influenced by oxidation state sulfur. Modeling studies sulfur might influence global shape isothiocyanates. These findings establish as target food-derived anti-inflammatory compounds.