Flavanones common to citrus fruits activate the interferon-stimulated response element by stimulating expression of IRF7

Citrus fruits are a rich source of vitamin C and phytochemicals and can be an important part of a healthy diet. Citrus is believed to prevent the occurrence or shorten the duration of symptoms of the common cold and influenza, but meta-analysis of vitamin C clinical trial data is inconclusive. We examined whether citrus flavonoids activated antiviral pathways that might explain the perceived efficacy against the common cold and influenza. We found that a citrus bioflavonoid blend augmented NFkB activation in the presence of imiquimod. In addition, the citrus bioflavonoid blend, as well as individual flavonoids found in the blend, activated the interferon-stimulated response element (ISRE). The ability to activate the ISRE appeared to due to the flavonoids’ ability to upregulate expression of the transcription factor interferon regulatory factor 7 (IRF7). Our results suggest that flavonoids from citrus may stimulate antiviral pathways due to their ability to activate the ISRE.