GIRK channel activity of Hungarian mushrooms: From screening to biologically active metabolites

Attila Ványolós; Péter Orvos; Bayar Chuluunbaatar; László Tálosi; Judit Hohmann

doi:10.1016/j.fitote.2019.104272

GIRK channel activity of Hungarian mushrooms: From screening to biologically active metabolites

Fitoterapia. 2019 Sep:137:104272. doi: 10.1016/j.fitote.2019.104272. Epub 2019 Jul 19.

Authors

Attila Ványolós¹, Péter Orvos², Bayar Chuluunbaatar³, László Tálosi³, Judit Hohmann⁴

Affiliations

¹ Department of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary. Electronic address: vanyolosa@pharmacognosy.hu.
² Department of Ophthalmology, University of Szeged, Korányi fasor 10-11, H-6720 Szeged, Hungary; Department of Pharmacology and Pharmacotherapy, University of Szeged, Dóm tér 12, H-6720 Szeged, Hungary.
³ Department of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
⁴ Department of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary; Interdisciplinary Centre for Natural Products, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.

PMID: 31326417
DOI: 10.1016/j.fitote.2019.104272

Abstract

In the current study effects of fungal extracts on the G-protein-activated inwardly rectifying potassium channel (GIRK1/4) were screened using the automated patch-clamp method. 40 organic (n-hexane, chloroform, and 50% methanol) and aqueous extracts were prepared from 10 mushroom species native to Hungary. Among the examined fungal fractions of different polarities some n-hexane and chloroform extracts exerted considerable ion channel activity. One of the most active fungal species, Hypholoma lateritium was selected for further detailed examination to determine the compounds responsible for the observed pharmacological property. Evaluation of the ion channel activity of mushroom metabolites 1-10 revealed that lanosta-7,9(11)-diene-12β,21α-epoxy-2α,3β,24β,25-tetraol (5) demonstrates remarkable blocking activity on GIRK current (IC₅₀ 395.1 ± 31.8 nM). Investigation of the selectivity of the GIRK inhibitory effect proved that lanosta-7,9(11)-diene-12β,21α-epoxy-2α,3β,24β,25-tetraol (5) has only weak inhibitory activity on hERG channel (7.9 ± 2.8% at 100 μM), exerting more than three orders of magnitude lower blocking activity on hERG channel than on GIRK channel.

Keywords: GIRK; Hypholoma lateritium; Ion channel; Mushroom; Triterpene; hERG.

MeSH terms

Agaricales / chemistry*
ERG1 Potassium Channel / antagonists & inhibitors*
G Protein-Coupled Inwardly-Rectifying Potassium Channels / antagonists & inhibitors*
HEK293 Cells
Humans
Hungary
Molecular Structure
Patch-Clamp Techniques

Substances

ERG1 Potassium Channel
G Protein-Coupled Inwardly-Rectifying Potassium Channels
KCNH2 protein, human
KCNJ5 protein, human