Inhibition of G protein-activated inwardly rectifying K+ channels by extracts of Polygonum persicaria and isolation of new flavonoids from the chloroform extract of the herb.
The G protein-activated inwardly rectifying K+ channel-modulatory activities of Polygonum persicaria extracts were investigated by using an automated patch-clamp method, with the aim of identifying natural sources of promising ion channel-blocking compounds. The chloroform extract of the whole plant at 0.1 mg/mL exhibited high G protein-activated inwardly rectifying K+ channel-inhibitory activity. Fractionation of this extract by vacuum liquid chromatography on RP-silica gel resulted in 6 fractions, which were evaluated for G protein-activated inwardly rectifying K+ channel-modulatory activity. RP-HPLC of the most active fractions afforded the main compounds 1-4 in pure form and a mixture containing the minor constituents. The structures were identified by means of UV, HRMS, and advanced NMR methods as 3-O-senecioyl-isorhamnetin (1), 3-O-angeloyl-isorhamnetin (2), 5,3',4',5'-tetramethoxy-6,7-methylenedioxyflavone (3), and 3,5,3',4',5'-pentamethoxy-6,7-methylenedioxyflavone (4). Compounds 1-4 are new natural products, though 4 was reported earlier as a synthetic compound. Neither the individual, nor the combined application of compounds 1-4 modified the G protein-activated inwardly rectifying K+ channel activity. However, a marked G protein-activated inwardly rectifying K+ current-inhibitory effect was detected on use of the HPLC eluates containing the minor compounds. These results indicate the presence of electrophysiologically active agents among the minor compounds.
Department of Pharmacognosy, University of Szeged, Szeged, Hungary.
Ildikó
I
Lajter
Department of Pharmacognosy, University of Szeged, Szeged, Hungary.
Andrea
A
Vasas
Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary.
Péter
P
Orvos
Rytmion Ltd., Szeged, Hungary.
Száva
S
Bánsághi
Rytmion Ltd., Szeged, Hungary.
László
L
Tálosi
Hungary Institute of Environmental Sciences, Szent István University, Szarvas, Hungary.
Gusztáv
G
Jakab
Gedeon Richter Plc., API Research and Development - Spectroscopic Research, Budapest, Hungary.
Zoltán
Z
Béni
Gedeon Richter Plc., API Research and Development - Spectroscopic Research, Budapest, Hungary.
Viktor
V
Háda
Department of Pharmacognosy, University of Szeged, Szeged, Hungary.
Peter
P
Forgo
Department of Pharmacognosy, University of Szeged, Szeged, Hungary.
Judit
J
Hohmann
D002725:Chloroform; D004952:Esters / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D015394:Molecular Structure; D018408:Patch-Clamp Techniques; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D028502:Polygonum / Q000737:chemistry*
D004952:Esters; D005419:Flavonoids; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D010936:Plant Extracts; D002725:Chloroform; D019204:GTP-Binding Proteins