Abstract
Context: Naringin (NRG) is the major flavonoid (flavanone glycoside) in grapefruit juice. Its biological activity has been only partially characterized and little is known about the mechanism of the negative inotropic action of this flavonoid. Aims: To evaluate the effects of NRG on the surface electrogram (ECG) and the force of contraction (FC) of mice hearts as well as on the sodium (INa), calcium (ICaL) and Na+ – Ca2+ exchange (INaCaX) currents of enzymatically isolated mouse ventricular cardiomyocytes. Methods: ECG and FC were recorded on mouse hearts perfused in a Langendorff column. Ventricular cardiomyocytes were enzimatically dissociated and ionic currents recorded with the patch-clamp technique. Results: NRG increased RR interval and shortened corrected QT only at high concentrations (30-100 µM). However, at a fixed heart rate, it decreased FC with an IC50 of 0.4 µM. NRG reduced INa with an IC50 of 0.07 µM but with a maximal inhibition of 60 %. NRG also depressed ICaL with an IC50 of 0.013 µM and increased its fast inactivation time constant. The effects on ICaL were not voltage-dependent. INaCaX was not affected by NRG. Conclusions: Our results indicate that NRG exerts a negative inotropic effect in mice hearts that could be explained by a decrease in INa and ICaL. These actions should be taken into account when considering this molecule either as a dietetic supplement or as a template to develop therapeutic agents for human diseases.
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