title: Human Ether-à-go-go Related Gene (hERG) Channel Blocking Aporphine Alkaloids from Lotus Leaves and Their Quantitative Analysis in Dietary Weight Loss Supplements.
abstract: Blockage of the human ether-à-go-go related gene (hERG) channel can result in life-threatening ventricular tachyarrhythmia. 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. 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.
authors.affiliation: †Institute of Pharmacy/Pharmacognosy, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Grienke
authors.affiliation: †Institute of Pharmacy/Pharmacognosy, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria.
authors.forename: Christina E
authors.initials: CE
authors.lastname: Mair
authors.forename: Priyanka
authors.initials: P
authors.lastname: Saxena
authors.forename: Igor
authors.initials: I
authors.lastname: Baburin
authors.affiliation: #Cytocentrics Bioscience GmbH, Tannenweg 22k, 18059 Rostock, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Scheel
authors.affiliation: †Institute of Pharmacy/Pharmacognosy, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Ganzera
authors.affiliation: ⊥Institute of Pharmacy/Pharmaceutical Chemistry, Computer-Aided Molecular Design Group, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Schuster
authors.forename: Steffen
authors.initials: S
authors.lastname: Hering
authors.affiliation: †Institute of Pharmacy/Pharmacognosy, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria.
authors.forename: Judith M
authors.initials: JM
authors.lastname: Rollinger
mesh_terms: D000470:Alkaloids / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D019440:Anti-Obesity Agents / Q000737:chemistry* / Q000494:pharmacology; D001060:Aporphines / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D019587:Dietary Supplements / Q000032:analysis*; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D031653:Nelumbo / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry* / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry*; D026902:Potassium Channel Blockers / Q000737:chemistry* / Q000494:pharmacology; D014981:Xenopus
chemical_list: D000470:Alkaloids; D019440:Anti-Obesity Agents; D001060:Aporphines; D051638:Ether-A-Go-Go Potassium Channels; D010936:Plant Extracts; D026902:Potassium Channel Blockers; C081279:aporphine
keywords: Nelumbo nucifera; cardiotoxic risk; dietary supplement; hERG; lotus; nuciferine; patch clamp assay; weight loss