Plant Occurring Flavonoids as Modulators of the Aryl Hydrocarbon Receptor.

Elizabeth Goya-Jorge,Maité Sylla-Iyarreta Veitía,Rosa M Giner,María Elisa Jorge Rodríguez

doi:10.3390/molecules26082315

Abstract

The aryl hydrocarbon receptor (AhR) is a transcription factor deeply implicated in health and diseases. Historically identified as a sensor of xenobiotics and mainly toxic substances, AhR has recently become an emerging pharmacological target in cancer, immunology, inflammatory conditions, and aging. Multiple AhR ligands are recognized, with plant occurring flavonoids being the largest group of natural ligands of AhR in the human diet. The biological implications of the modulatory effects of flavonoids on AhR could be highlighted from a toxicological and environmental concern and for the possible pharmacological applicability. Overall, the possible AhR-mediated harmful and/or beneficial effects of flavonoids need to be further investigated, since in many cases they are contradictory. Similar to other AhR modulators, flavonoids commonly exhibit tissue, organ, and species-specific activities on AhR. Such cellular-context dependency could be probably beneficial in their pharmacotherapeutic use. Flavones, flavonols, flavanones, and isoflavones are the main subclasses of flavonoids reported as AhR modulators. Some of the structural features of these groups of flavonoids that could be influencing their AhR effects are herein summarized. However, limited generalizations, as well as few outright structure-activity relationships can be suggested on the AhR agonism and/or antagonism caused by flavonoids.

Highlights

Flavonoids are the largest class of phenolic compounds found in nature, important in the plant kingdom
The aglycone and glycoside forms of flavonoids are found in the human daily diet like fruits, vegetables, grains, seeds, bark, herbs, roots, flowers, stems, and spices
Despite several decades of research on flavonoid derivatives, these ubiquitous constituents of food remain surprising for their bioactivity profiles

Summary

Introduction

Flavonoids are the largest class of phenolic compounds found in nature, important in the plant kingdom. Flavonoids are responsible for the color and flavor [1]. The aglycone and glycoside (i.e., glucosides, rhamnoglucosides, and rutinosides) forms of flavonoids are found in the human daily diet like fruits, vegetables, grains, seeds, bark, herbs, roots, flowers, stems, and spices. The natural distribution of these plant secondary metabolites, their inherent structural diversity, chemical properties, and ability to interact with biological systems modifying multiple target receptors in mammalians, have attracted attention during decades to their study in pharmacological and toxicological contexts [2,3]. Among the wide range of biological properties referable to flavonoids are included antioxidant, anti-inflammatory, antitumor, antiviral, hypolipidemic, antithrombotic, estrogenic, and antiallergic activities. Numerous pre-clinical and epidemiological studies reveal that flavonoids may exert protective effects against chronic conditions such as cancer, diabetes, and cardiovascular and neurodegenerative diseases, supporting the concept of a beneficial role for dietary flavonoids in human health [4,5,6,7]

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