Supplementary Material for: Additive Effects of Citrus Juice Flavonoid Naringenin and Statins on HERG Channels Expressed in Xenopus Oocytes

Objective: Naringenin, a major flavonoid found in citrus juice, has been shown to inhibit HERG channels and cause QT prolongation. Statins, the most commonly used class of cholesterol reducing drugs, have also been reported to inhibit HERG channels and prolong QT interval in patients using these drugs. However, the interaction between naringenin and statins on the function of HERG channels has not been studied. Materials and Methods: In the present study, we expressed HERG channels in Xenopus oocytes and tested the effects of naringenin and statins separately and combined on HERG channels. Results: When 30 µM naringenin was added to statins (1 µM rosuvastatin or 3 µM atorvastatin), significantly greater inhibition of HERG was demonstrated, compared to the inhibition caused by statins alone. Conclusions: The results indicate that an additive interaction occurs between naringenin and statins; this could pose an increased risk of arrhythmias by decreasing repolarization reserve.