Propolis as a potential modulator of aryl hydrocarbon receptor signaling in inflammation

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that exhibits antagonistic pleiotropy, mediating both protective and detrimental cellular effects depending on the ligand and context. AhR can be activated by a variety of endogenous and exogenous stimuli, including environmental pollutants, UVB radiation, heme, arachidonic acid metabolites, gut microbiota–derived compounds, and xenobiotics. Upon activation, AhR translocates to the nucleus, where it dimerizes with the aryl hydrocarbon receptor nuclear translocator (ARNT) and binds to xenobiotic response elements, inducing the expression of genes involved in xenobiotic metabolism, oxidative stress responses, and inflammatory signaling. In addition to these classical pathways, AhR also modulates immune function by regulating cytokine networks, including IL-17, IL-22, and IL-10, which play key roles in barrier integrity and immune homeostasis. Bioactive dietary compounds, particularly polyphenols such as flavonoids, have emerged as potential modulators of AhR signaling. Propolis, a complex bee-derived product rich in flavonoids and other phenolic compounds, has demonstrated antioxidant and anti-inflammatory effects across multiple experimental models. However, the specific mechanisms through which propolis interacts with AhR signaling remain poorly understood. This mini-review summarizes current evidence on the potential role of propolis as an AhR modulator, discusses its implications for immune regulation, barrier function, and inflammation control, and highlights areas for future research.