Natural products modulating the hERG channel: heartaches and hope

Area of Science:

• Cardiovascular Pharmacology
• Ion Channel Physiology
• Natural Product Chemistry

Background:

• The human Ether-à-go-go Related Gene (hERG) channel is vital for cardiac electrical activity, regulating repolarization.
• hERG channel dysfunction, due to gene mutations or small molecule blockage, increases the risk of fatal cardiac arrhythmias.
• hERG channel blockers have led to drug withdrawals, highlighting its importance as an antitarget in drug discovery.

Purpose of the Study:

• To critically compile hERG channel data for natural products and extracts from 1996-2016.
• To provide a molecular understanding of hERG channel functions and their clinical relevance.
• To explore strategies for identifying hERG channel blockers from natural sources and their implications for cardiac safety.

Main Methods:

• Comprehensive literature review of studies published between 1996 and 2016.
• Compilation and critical analysis of hERG channel blocking data for isolated natural products and botanical extracts.
• Assessment of the translational potential of in vitro/in vivo findings to human cardiotoxicity.

Main Results:

• Identified a significant body of research on hERG channel interactions with natural compounds over two decades.
• Highlighted the lack of routine assessment for hERG channel blocking profiles of commonly consumed botanicals.
• Detailed the known cardiotoxic risks associated with hERG channel modulation by natural products.

Conclusions:

• Natural compounds in dietary supplements and herbal products can interact with the hERG channel, posing potential cardiac risks.
• There is a need for systematic evaluation of hERG channel activity in phytopharmaceuticals and dietary supplements.
• Future research should focus on developing cardiac safety guidelines and exploring novel therapeutic applications of hERG channel modulation.