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The grapefruit polyphenol naringenin inhibits multiple cardiac ion channels

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Drinking fresh grapefruit juice is associated with a significant prolongation of the QT segment on the electrocardiogram (ECG) in healthy volunteers. Among the prominent polyphenols contained in citrus fruits and primarily in grapefruit, the flavonoid naringenin is known to be a blocker of the human ether-a-go-go related gene (hERG) potassium channel. Here we hypothesized that naringenin could interfere with other major ion channels shaping the cardiac ventricular action potential (AP). To test this hypothesis, we examined the effects of naringenin on the seven channels comprising the Comprehensive in vitro Pro-Arrhythmia (CiPA) ion channel panel for early arrhythmogenic risk assessment in drug discovery and development. We used automated population patch-clamp of human ion channels heterologously expressed in mammalian cells to evaluate half-maximal inhibitory concentrations (IC50). Naringenin blocked all CiPA ion channels tested with IC50 values in the 30–100 µM concentration-range. The rank-order of channel sensitivity was the following: hERG > Kir2.1 > NaV1.5 (late current) > NaV1.5 (peak current) > KV7.1 > KV4.3 > CaV1.2. This multichannel inhibitory profile of naringenin suggests exercising caution when large amounts of grapefruit juice or other citrus juices enriched in this flavonoid polyphenol are drunk in conjunction with QT prolonging drugs or by carriers of congenital long-QT syndromes.

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Fig. 1

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All data are included as a supplemental Prism file.


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The authors are grateful to Fiona Ducrey for language revision.

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Authors and Affiliations



MP and GAB designed and supervised the study. CS, RB, SH, MAM, and SF generated and curated the data. GAB wrote the manuscript. All authors read and approved the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to G. Andrees Bohme.

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All authors are current or former Sanofi employees and may hold shares and/or stock options in the company.

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Sanson, C., Boukaiba, R., Houtmann, S. et al. The grapefruit polyphenol naringenin inhibits multiple cardiac ion channels. Naunyn-Schmiedeberg's Arch Pharmacol 395, 735–740 (2022).

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