Key result
Eight plant alkaloids inhibit hERG current by ≥50% in an automated oocyte assay.
Why the study?
The human ether-a-go-go-related gene channel inhibition by plant-derived compounds is poorly understood despite its clinical safety importance.
May signal arrhythmia risk from herbal alkaloids; leaves open clinical relevance from oocyte assay data.
Inhibition of the cardiac human ether-a-go-go-related gene channel is a problematic off-target pharmacological activity and, hence, a major safety liability in clinical practice. Several non-cardiac drugs have been restricted in their use, or even removed from the market due to this potentially fatal adverse effect. Comparatively little is known about the human ether-a-go-go-related gene inhibitory potential of plant-derived compounds. In the course of an ongoing human ether-a-go-go-related gene in vitro study, a total of 32 structurally diverse alkaloids of plant origin as well as two semi-synthetically obtained protoberberine derivatives were screened by means of an automated Xenopus oocyte assay. Protopine, (+)-bulbocapnine, (+)-N-methyllaurotetanine, (+)-boldine, (+)-chelidonine, (+)-corynoline, reserpine, and yohimbine reduced the human ether-a-go-go-related gene current by ≥ 50% at 100 µM, and were submitted to concentration-response experiments. Our data show that some widely occurring plant-derived alkaloids carry a potential risk for human ether-a-go-go-related gene toxicity.
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Schramm et al. (2014) studied Human ether-a-go-go-related gene (hERG) toxicity. Plant-derived alkaloids and protoberberine derivatives was evaluated on Reduction of human ether-a-go-go-related gene current by ≥50%. Eight plant-derived alkaloids, including protopine, reserpine, and yohimbine, reduced the human ether-a-go-go-related gene current by ≥50% at 100 µM in an automated Xenopus oocyte assay.
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