title: Natural products as potential human ether-a-go-go-related gene channel inhibitors - outcomes from a screening of widely used herbal medicines and edible plants.
abstract: Inhibition of the human ether-a-go-go-related gene channel is the single most important risk factor leading to acquired long QT syndrome. Drug-induced QT prolongation can cause severe cardiac complications, including arrhythmia, and is thus a liability in drug development. Considering the importance of the human ether-a-go-go-related gene channel as an antitarget and the daily intake of plant-derived foods and herbal products, surprisingly few natural products have been tested for channel blocking properties. In an assessment of possible human ether-a-go-go-related gene liabilities, a selection of widely used herbal medicines and edible plants (vegetables, fruits, and spices) was screened by means of a functional two-microelectrode voltage-clamp assay with Xenopus oocytes. The human ether-a-go-go-related gene channel blocking activity of selected extracts was investigated with the aid of a high-performance liquid chromatography-based profiling approach, and attributed to tannins and alkaloids. Major European medicinal plants and frequently consumed food plants were found to have a low risk for human ether-a-go-go-related gene toxicity.
authors.affiliation: Division of Pharmaceutical Biology, University of Basel, Basel, Switzerland.
authors.forename: Anja
authors.initials: A
authors.lastname: Schramm
authors.affiliation: Division of Pharmaceutical Biology, University of Basel, Basel, Switzerland.
authors.forename: Evelyn A
authors.initials: EA
authors.lastname: Jähne
authors.affiliation: Institute of Pharmacology and Toxicology, University of Vienna, Vienna, Austria.
authors.forename: Igor
authors.initials: I
authors.lastname: Baburin
authors.affiliation: Institute of Pharmacology and Toxicology, University of Vienna, Vienna, Austria.
authors.forename: Steffen
authors.initials: S
authors.lastname: Hering
authors.affiliation: Division of Pharmaceutical Biology, University of Basel, Basel, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hamburger
mesh_terms: D000470:Alkaloids / Q000009:adverse effects / Q000494:pharmacology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D001688:Biological Products; D053840:Brugada Syndrome; D000075224:Cardiac Conduction System Disease; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors*; D006329:Heart Conduction System / Q000002:abnormalities*; D029001:Herbal Medicine; D006801:Humans; D009865:Oocytes; D010936:Plant Extracts / Q000009:adverse effects / Q000494:pharmacology*; D010945:Plants, Edible / Q000737:chemistry*; D010946:Plants, Medicinal / Q000737:chemistry*; D026902:Potassium Channel Blockers / Q000009:adverse effects / Q000494:pharmacology*; D013634:Tannins / Q000009:adverse effects / Q000494:pharmacology; D014981:Xenopus
chemical_list: D000470:Alkaloids; D001688:Biological Products; D051638:Ether-A-Go-Go Potassium Channels; D010936:Plant Extracts; D026902:Potassium Channel Blockers; D013634:Tannins