Intrinsic bitterness of flavonoids and isoflavonoids and masking of their taste activity

The presence of flavonoids and isoflavonoids in foods and their addition as bioactives to food products can impart unpleasant bitterness. Therefore, debittering strategies are demanded. The aim of this research was to identify human bitter receptors (hTAS2Rs) sensing (iso)flavonoids and to determine the intrinsic bitterness and structure-activity relationships of soy isoflavones, tea catechins and a large set of structurally similar (iso)flavonoids by testing for activation of hTAS2Rs in vitro. A subsequent aim was to use the bitter receptor assay for investigation of different debittering strategies.

Promovendus WSU (Wibke) Roland
Promotor H (Harry) Gruppen
Copromotor JP (Jean-Paul) Vincken
Organisatie Wageningen University, Laboratory of Food Chemistry

vr 25 april 2014 16:00 tot 17:30

Locatie Auditorium, building number 362
Generaal Foulkesweg 1
6703 BG Wageningen

Out of all 25 human bitter taste receptors, hTAS2R14 and hTAS2R39, were activated by soy isoflavones. hTAS2R14 was only activated by isoflavone aglycones, whereas hTAS2R39 was activated by isoflavone glucosides as well. Investigation of almost 100 (iso)flavonoid aglycones for activation of hTAS2R14 and hTAS2R39 revealed that many (iso)flavonoids activated these receptors.

The structural characteristics for an (iso)flavonoid to activate hTAS2R14 and hTAS2R39 were determined by 3D-pharmacophore models to be composed of two (for hTAS2R14) or three (for hTAS2R39) hydrogen bond donor sites, one hydrogen bond acceptor site, and two aromatic ring structures, of which one had to be hydrophobic. 

Reduced bitterness perception

Three 6-methoxyflavanones were identified which reduced activation of hTAS2R39 by epicatechin gallate (ECG). These bitter receptor blockers were characterized as reversible insurmountable antagonists. Furthermore, complexation of epigallocatechin gallate (EGCG) with food proteins (mainly β-casein and Na-caseinates) reduced hTAS2R39 activation. A trained sensory panel confirmed reduced bitterness perception.

The systematic investigation of (iso)flavonoid aglycones indicated that the substitution pattern of (iso)flavonoids is of higher importance for bitter receptor activation than the backbone structure. In case of bitter receptor antagonists, the substitution pattern as well as backbone structure revealed to be crucial for functionality. The bitter receptor assay was shown to be an appropriate tool not only for identification of bitter receptor agonists and antagonists, but also for identification of reduced receptor activation by complexing agents.