Planta Med 2014; 80 - SL45
DOI: 10.1055/s-0034-1394533

The 'Lotus Leave Diet' – A life-threatening experience? hERG channel blocking aporphine alkaloids from Nelumbo nucifera Gaertn

U Grienke 1, CE Mair 1, P Saxena 2, JM Kratz 3, I Baburin 2, D Schuster 4, S Hering 2, JM Rollinger 1
  • 1Institute of Pharmacy/Pharmacognosy, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 80 – 82, 6020 Innsbruck, Austria
  • 2Department of Pharmacology and Toxicology, University of Vienna, Althanstraße 14, 1090 Vienna, Austria
  • 3Departamento de Ciencias Farmaceuticas, Universidade Federal de Santa Catarina, 88.040 – 900, Florianopolis, SC, Brazil
  • 4Institute of Pharmacy/Pharmaceutical Chemistry, Computer-Aided Molecular Design Group, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 80 – 82, 6020 Innsbruck, Austria

The human Ether-a-go-go Related Gene (hERG) potassium channel is responsible for sending an electrical current across the cell membrane and plays a key role during the repolarisation phase of the cardiac action potential. An interference or blockage of this ion channel can result in ventricular tachyarrhythmia, a long QT syndrome, and in an increased incidence of sudden deaths [1]. In the “hERGscreen” project, the aim is to identify hERG blockers by screening extracts or fractions of commonly consumed herbal materials in a fast and reliable in vitro assay on Xenopus oocytes [2]. Here, supported by virtual predictions of a recently generated pharmacophore model [3], an alkaloid fraction of Nelumbo nucifera Gaertn. (lotus) leaves revealed 50% hERG channel inhibition at 100 µg/mL. Lotus leaves are widely advertised as herbal supplements to achieve weight loss without any side effects. Currently, this is known as the “lotus leave diet”. To further characterize the hERG blocking activity of N. nucifera alkaloids, separation was performed via liquid liquid chromatography using fast centrifugal partition chromatography (FCPC). As a result, four aporphine-type alkaloids, i.e. nuciferine (1), (-)-asimilobine (2), O-nornuciferine (3), and N-nornuciferine (4), and one isoquinoline-type alkaloid, i.e. liensinine (5) were isolated and structurally identified. At 100µM, compounds 1, 3, and 4 revealed distinct hERG blocking activities in the range of 45 to 80%. This study provides insight into predicted ligand-target interactions and phytochemical analyses of respective materials which underline the high relevance of these findings concerning a possible restriction in the use of lotus herbal supplements as dietary products.

Acknowledgements: Supported by a Marie Curie International Research Staff Exchange Scheme Fellowship within the 7th European Community Framework Programme (hERGscreen, 295174). DS is grateful for her position in the Erika Cremer Habilitation Program of the University of Innsbruck.

Keywords: hERG channel, Nelumbo nucifera, lotus, virtual prediction

References:

[1] Sanguinetti et al. 2006, Nature 440, 463.

[2] Schramm et al. 2011, Planta Med. 77, 692.

[3] Kratz et al. 2014, in revision.