Blockage of the human ether-à-go-go related gene (hERG) channel can result in life-threatening ventricular tachyarrhythmia. METHODS AND RESULTS: In an in vitro screening of herbal materials for hERG blockers using an automated two-microelectrode voltage clamp assay on Xenopus oocytes, an alkaloid fraction of Nelumbo nucifera Gaertn. (lotus) leaves induced ~50% of hERG current inhibition at 100 μg/mL. Chromatographic separation resulted in the isolation and identification of (-)-asimilobine, 1, nuciferine, 2, O-Nornuciferine, 3, N-nornuciferine, 4, and liensinine, 5. In agreement with in silico predicted ligand-target interactions, 2, 3, and 4 revealed distinct in vitro hERG blockages measured in HEK293 cells with IC50 values of 2.89, 7.91, and 9.75 μM, respectively.
CONCLUSIONS:
Because lotus leaf dietary weight loss supplements are becoming increasingly popular, the identified hERG-blocking alkaloids were quantitated in five commercially available products.
Results showed pronounced differences in the content of hERG-blocking alkaloids ranging up to 992 μg (2) in the daily recommended dose.
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