The molecular mechanisms underlying the observed anticancer effects of flavonoids remain unclear. Increasing evidence shows that the aryl hydrocarbon receptor (AHR) plays a crucial role in neoplastic disease progression, establishing it as a potential drug target. This study evaluated the potential of hydroxy flavonoids, known for their anticancer properties, to interact with AHR, both in silico and in vitro, aiming to understand the mechanisms of action and identify selective AHR modulators. A PAS-B domain homology model was constructed to evaluate in silico interactions of chrysin, naringenin, quercetin apigenin and agathisflavone. The EROD activity assay measured the effects of flavonoids on AHR’s activity in human breast cancer cells (MCF7). Simulations showed that chrysin, apigenin, naringenin, and quercetin have the highest AHR binding affinity scores (−13.14 to −15.31), while agathisflavone showed low scores (−0.57 and −5.14). All tested flavonoids had the potential to inhibit AHR activity in a dose-dependent manner in the presence of an agonist (TCDD) in vitro. This study elucidates the distinct modulatory effects of flavonoids on AHR, emphasizing naringenin’s newly described antagonistic potential. It underscores the importance of understanding flavonoid’s molecular mechanisms, which is crucial for developing novel cancer therapies based on these molecules.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by neuroinflammation and demyelination. Although treatment options for MS have increased over the past decade, current therapies primarily target the peripheral immune system and are often associated with significant side effects. Moreover, these therapies still do not offer solutions for the resulting neurodegeneration that accompanies the progression of the disease. Findings from research using cellular and animal models and studies in humans highlight the neuroprotective and anti-inflammatory properties of apigenin, a flavonoid present in several commonly consumed plant species, such as cabbage, orange, tea, onion, and chamomile. This review compiles chemical and current evidence on the therapeutic potential of apigenin, primarily on its ability to modulate neuroinflammation and underscore the need for further investigation into its clinical applications as an adjuvant therapy for MS.