# Phytochemical-Mediated Ah Receptor Activity Is Dependent on Dietary Context

## TL;DR

This study shows that certain vegetables can activate the AHR in mice, and their effects depend on the combination of foods consumed.

## Contribution

The study demonstrates that dietary context modulates AHR activity through phytochemical interactions in vivo.

## Key findings

- Broccoli, onion, and carrots increased Cyp1a1 gene expression in the duodenum.
- Parsley enhanced broccoli's effect on Cyp1a1 induction in multiple organs.
- Apigenin from parsley can influence ICZ metabolism and AHR activation.

## Abstract

Background/Objective: The aryl hydrocarbon receptor (AHR) is an important mediator of intestinal homeostasis. The AHR senses certain classes of phytochemicals, including many flavonoids and tryptophan metabolites generated in the intestinal tract. Several in vitro studies demonstrate the presence of AHR ligands in numerous plants commonly consumed by humans. However, it has not been established that these foods can activate the AHR in vivo. The aim of this study was to evaluate how phytochemicals in foods can lead to AHR activation in vivo through modulating CYP1A1 activity. Methods: Freeze-dried spinach, corn, red potatoes, kidney beans, parsley, onion, carrots, bell peppers, and broccoli were fed to C57BL6/J female mice at 15% w/w in a semi-purified diet to evaluate the AHR activation potential. In vitro CYP1A1 microsomal assays were utilized to establish specific phytochemicals as CYP1A1 substrates. Results: Broccoli, onion, and carrots increased expression of the AHR target gene Cyp1a1 in the duodenum. Broccoli consumption led to the formation of the potent AHR ligand indolo[3,2-b]carbazole (ICZ), which is also a CYP1A1 substrate. Relative to the other vegetables, parsley contained a high concentration of apiin, a diglycoside of the flavone apigenin. Mice were fed a diet with either 10% parsley, 10% broccoli, or both vegetables. Parsley consumption increased broccoli-mediated Cyp1a1 induction in the duodenum, liver, and lung. Apigenin is a CYP1A1 substrate that can attenuate ICZ metabolism in vitro and increase broccoli-mediated Cyp1a1 expression in the lung. Conclusions: These results suggest that phytochemical competition for intestinal AHR binding and CYP1A1 metabolism modulates systemic AHR activity.