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2019 - GIRK channel activity of Hungarian mushrooms: From screening to biologically active metabolites

icon pl   Patchliner publication in Fitoterapia (2019)

Authors:
Ványolósa A., Orvos P., Chuluunbaatar B., Tálosi L., Hohmann J.

Journal:
Fitoterapia (2019) 137: 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-epoxy2α,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-epoxy2α,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.

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