title: Identification of diterpene alkaloids from Aconitum napellus subsp. firmum and GIRK channel activities of some Aconitum alkaloids.
abstract: Diterpene alkaloids neoline (1), napelline (2), isotalatizidine (3), karakoline (4), senbusine A (5), senbusine C (6), aconitine (7) and taurenine (8) were identified from Aconitum napellus L. subsp. firmum, four (2-4, 6) of which are reported for the first time from this plant. The structures were determined by means of LC-MS, 1D and 2D NMR spectroscopy, including (1)H-(1)H COSY, NOESY, HSQC and HMBC experiments. Electrophysiological effects of the isolated compounds, together with nine diterpene alkaloids previously obtained from Aconitum toxicum and Consolida orientalis were investigated on stable transfected HEK-hERG (Kv11.1) and HEK-GIRK1/4 (Kir3.1 and Kir3.4) cell lines using automated patch clamp equipment. Significant blocking activity on GIRK channel was exerted by aconitine (7) (45% at 10 μM), but no blocking activities of the other investigated compounds were detected. The tested compounds were inactive on hERG channel in the tested concentration. The comparison of the previously reported metabolites of A. napellus subsp. firmum and compounds identified in our experiment reveals substantial variability of the alkaloid profile of this taxon.
authors.affiliation: Department of Pharmacognosy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
authors.forename: Tivadar
authors.initials: T
authors.lastname: Kiss
authors.forename: Péter
authors.initials: P
authors.lastname: Orvos
authors.forename: Száva
authors.initials: S
authors.lastname: Bánsághi
authors.forename: Peter
authors.initials: P
authors.lastname: Forgo
authors.forename: Nikoletta
authors.initials: N
authors.lastname: Jedlinszki
authors.forename: László
authors.initials: L
authors.lastname: Tálosi
authors.forename: Judit
authors.initials: J
authors.lastname: Hohmann
authors.forename: Dezső
authors.initials: D
authors.lastname: Csupor
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D031841:Aconitum / Q000737:chemistry*; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D029626:Ranunculaceae / Q000737:chemistry
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C000606913:KCNH2 protein, human; D010936:Plant Extracts; D026902:Potassium Channel Blockers; C487396:neoline; C109326:napelline; C423465:isotalatizidine; D000157:Aconitine
keywords: Aconitum napellus L. subsp. firmum; Cardiovascular ion channels; Diterpene alkaloids; GIRK; hERG