Background:

The Aryl hydrocarbon receptor (AHR) plays a significant role in the development of the mammary gland, as it is related to the transforming growth factor β1 (TGF-β1), which regulates several cellular processes. Hence, its overexpression may lead to pathological processes in the animals, and affect their health and production.

Materials and methods:

The 3-methyl luteoline, kaempferol, resveratrol, myricetin, and quercetin flavonoid molecules were studied. Modelling relied on the AHR:ARNT structures obtained from Swiss Model software, for coupling program MOE 2019.01, and to determine the protein-protein interactions (PPI). The Cocomaps (bioComplexes Contact MAPS) servers, and Robetta and Rosetta Backruband were used for determining the mutations of alanine.

Results:

The flavonoids studied associated with contact interfaces at the bHLH, PAS-A domain level and the bHLH/PAS-A and PAS-A/PAS-B of AHR interfaces, and they can undergo an antagonistic behavior due to the interactions at the contact surface level to block or modulate the protein-protein interactions between AHR and ARNT.

Conclusions

The five flavonoids can interact at different AHR superficial interfaces to modulate the formation of the functional heterodimer, acting as antagonist agents. The order of occurrence probability of these actions is higher with 3-methyl luteoline, kaempferol, resveratrol, and lower with myricetin, and quercetin. Feed supplementation using foliage rich in these flavonoids might improve animal health and production.