当前位置： SCI文献检索 > EUROPEAN JOURNAL OF PHARMACOLOGY期刊下所有文献 > Hops compounds modulatory effects and 6-prenylnaringenin dual mode of action on GABAA receptors.

Hops compounds modulatory effects and 6-prenylnaringenin dual mode of action on GABAA receptors.

Abstract：

:Hops (Humulus lupulus L.), a major component of beer, contain potentially neuroactive compounds that made it useful in traditional medicine as a sleeping aid. The present study aims to investigate the individual components in hops acting as allosteric modulators in GABAA receptors and bring further insight into the mode of action behind the sedative properties of hops. GABA-potentiating effects were measured using [3H]ethynylbicycloorthobenzoate (EBOB) radioligand binding assay in native GABAA receptors. Flumazenil sensitivity of GABA-potentiating effects, [3H]Ro 15-4513, and [3H]flunitrazepam binding assays were used to examine the binding to the classical benzodiazepines site. Humulone (alpha acid) and 6-prenylnaringenin (prenylflavonoid) were the most potent compounds displaying a modulatory activity at low micromolar concentrations. Humulone and 6-prenylnaringenin potentiated GABA-induced displacement of [3H]EBOB binding in a concentration-dependent manner where the IC50 values for this potentiation in native GABAA receptors were 3.2 μM and 3.7 μM, respectively. Flumazenil had no significant effects on humulone- or 6-prenylnaringenin-induced displacement of [3H]EBOB binding. [3H]Ro 15-4513 and [3H]flunitrazepam displacements were only minor with humulone but surprisingly prominent with 6-prenylnaringenin despite its flumazenil-insensitive modulatory activity. Thus, we applied molecular docking methods to investigate putative binding sites and poses of 6-prenylnaringenin at the GABAA receptor α1β2γ2 isoform. Radioligand binding and docking results suggest a dual mode of action by 6-prenylnaringenin on GABAA receptors where it may act as a positive allosteric modulator at α+β- binding interface as well as a null modulator at the flumazenil-sensitive α+γ2- binding interface.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Benkherouf AY,Logrén N,Somborac T,Kortesniemi M,Soini SL,Yang B,Salo-Ahen OMH,Laaksonen O,Uusi-Oukari M

doi

10.1016/j.ejphar.2020.172962

subject

Has Abstract

pub_date

2020-04-15 00:00:00

pages

172962

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(20)30054-6

journal_volume

873

pub_type

杂志文章

在线工具

Hops compounds modulatory effects and 6-prenylnaringenin dual mode of action on GABAA receptors.