Anti-Inflammation Activity of Flavones and Their Structure-Activity Relationship

Flavones are an important class of bioactive constituents in foods, and their structural diversity enables them to interact with different targets. In particular, flavones are known for their anti-inflammatory activity. Herein, we summarized commonly applied in vitro, in vivo, and clinical models in testing anti-inflammatory activity of flavones. The anti-inflammatory structure-activity relationship of flavones was systematically mapped and supported with cross comparisons of that with flavanones, flavanols, and isoflavones. Hydroxyl groups (-OH) are indispensable for the anti-inflammatory function of flavones, and -OH at the C-5 and C-4' positions enhance while -OH at the C-6, C-7, C-8, and C-3' positions attenuate their activity. Moreover, the C2-C3 single bond, -OH at the C-3 and B-ring positions undermine flavone aglycones' activity. Most of the flavone aglycones function through NF-κB, MAPK, and JNK-STAT pathways, and their possible cell binding targets are kinase, aryl hydrocarbon receptor (AhR), G-protein coupled receptors, and estrogen receptors. However, the structure and anti-inflammatory activity relationship of flavones were unclear, and further research shall be conducted to close the gap in order to guide development of evidence-based functional foods.