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Issue 8, 2017
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Natural products modulating the hERG channel: heartaches and hope

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Abstract

Covering: 1996–December 2016

The human Ether-à-go-go Related Gene (hERG) channel is a voltage-gated potassium channel playing an essential role in the normal electrical activity in the heart. It is involved in the repolarization and termination of action potentials in excitable cardiac cells. Mutations in the hERG gene and hERG channel blockage by small molecules are associated with increased risk of fatal arrhythmias. Several drugs have been withdrawn from the market due to hERG channel-related cardiotoxicity. Moreover, as a result of its notorious ligand promiscuity, this ion channel has emerged as an important antitarget in early drug discovery and development. Surprisingly, the hERG channel blocking profile of natural compounds present in frequently consumed botanicals (i.e. dietary supplements, spices, and herbal medicinal products) is not routinely assessed. This comprehensive review will address these issues and provide a critical compilation of hERG channel data for isolated natural products and extracts over the past two decades (1996–2016). In addition, the review will provide (i) a solid basis for the molecular understanding of the physiological functions of the hERG channel, (ii) the translational potential of in vitro/in vivo results to cardiotoxicity in humans, (iii) approaches for the identification of hERG channel blockers from natural sources, (iv) future perspectives for cardiac safety guidelines and their applications within phytopharmaceuticals and dietary supplements, and (v) novel applications of hERG channel modulation (e.g. as a drug target).

Graphical abstract: Natural products modulating the hERG channel: heartaches and hope

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Supplementary files

Article information


Submitted
16 Feb 2017
First published
12 May 2017

This article is Open Access

Nat. Prod. Rep., 2017,34, 957-980
Article type
Review Article

Natural products modulating the hERG channel: heartaches and hope

J. M. Kratz, U. Grienke, O. Scheel, S. A. Mann and J. M. Rollinger, Nat. Prod. Rep., 2017, 34, 957
DOI: 10.1039/C7NP00014F

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