Natural Products as Potential Human Ether-a-Go-Go-Related Gene Channel Inhibitors – Outcomes from a Screening of Widely Used Herbal Medicines and Edible Plants

Abstract

Inhibition of the human ether-a-go-go-related gene channel is the single most important risk factor leading to acquired long QT syndrome. Drug-induced QT prolongation can cause severe cardiac complications, including arrhythmia, and is thus a liability in drug development. Considering the importance of the human ether-a-go-go-related gene channel as an antitarget and the daily intake of plant-derived foods and herbal products, surprisingly few natural products have been tested for channel blocking properties. In an assessment of possible human ether-a-go-go-related gene liabilities, a selection of widely used herbal medicines and edible plants (vegetables, fruits, and spices) was screened by means of a functional two-microelectrode voltage-clamp assay with Xenopus oocytes. The human ether-a-go-go-related gene channel blocking activity of selected extracts was investigated with the aid of a high-performance liquid chromatography-based profiling approach, and attributed to tannins and alkaloids. Major European medicinal plants and frequently consumed food plants were found to have a low risk for human ether-a-go-go-related gene toxicity.

Key words

herbal drugs - dietary plants - hERG channel inhibition - Xenopus oocyte assay - HPLC-based activity profiling - alkaloids

• References

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