hERG channel blockers in medicinal plants: Hysteria or serious problem?

A blockage of the human Ether-à-go-go Related Gene (hERG) channel is associated with QT interval prolongation in the electrocardiogram and an increased risk of fatal arrhythmias. In early drug discovery and development, candidate compounds are tested against this important antitarget in a standard procedure. Surprisingly, the hERG channel blocking profile of natural compounds present in frequently consumed botanicals, such as dietary supplements, spices, and herbal medicinal products, is not routinely assessed. In the recently accomplished EU funded project 'hERG related risk assessment of botanicals' (PIRSES-GA-2011 – 295174), a consortium of nine partners from three different continents committed themselves to the evaluation of putatively hERG channel blocking properties of commonly consumed herbal remedies. The project aimed at the critical assessment of hERG channel related toxicity to improve consumer and patient safety. Intriguingly, of more than 1,200 extracts probed in this endeavour, only ˜2.5% reduced the hERG channel peak tail current by ≥30% at 100 µg/mL in a voltage-clamp assay using Xenopus oocytes.

Here, examples and strategies for the identification of hERG blockers from medicinal plants will be presented [1 – 3]. This includes also a critical view on the relevance of these findings and a concluding discussion of the outcome of the hERGscreen project.

This work was supported by a Marie Curie IRSES Fellowship within the Seventh European Community Framework Programme (hERGscreen, 295174).

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