Flavonoids and hERG channels: Friends or foes?

Area of Science:

• Pharmacology
• Cardiology
• Natural Products Chemistry

Background:

• Cardiac action potential is regulated by ion channels.
• Blockade of the human ether-à-go-go-related gene (hERG) channel can cause Torsades de Pointes, a lethal arrhythmia.
• Drug development requires hERG channel safety assessment.

Purpose of the Study:

• To review the current understanding of flavonoid interactions with the hERG channel.
• To summarize evidence of direct and indirect hERG channel inhibition by flavonoids.
• To present in silico molecular interactions between flavonoids and the hERG channel.

Main Methods:

• Literature review of studies on flavonoids and hERG channel activity.
• Analysis of direct and indirect inhibition mechanisms.
• In silico modeling of flavonoid-hERG channel interactions.

Main Results:

• Flavonoids, despite dietary prevalence, often lack hERG channel safety assessments.
• Growing evidence shows flavonoids can directly or indirectly inhibit hERG channel function.
• In silico studies provide insights into molecular mechanisms of flavonoid-hERG interactions.

Conclusions:

• Flavonoids pose a potential risk for hERG channel-mediated cardiotoxicity.
• Further evaluation of hERG channel activity for flavonoids is crucial for patient safety.
• Understanding these interactions aids in drug development and dietary supplement safety.