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Evidence for the involvement of a GABAergic mechanism in the effectiveness of natural and synthetically modified incensole derivatives in neuropharmacological disorders: A computational and pharmacological approach.

Abstract：

:In the course of our continuing exploration for novel bioactive lead compounds (s) from the species Boswellia, we have recently reported incensole derivatives isolated from Boswellia papyrifera Hochst. Given the known antidepressant-like effects of incensole and incensole acetate, we herein present that the low dose intraperitoneal administration of incensole derivatives, namely, incensfuran and incensone, showed significant antidepressant-like effects in the forced swim test (FST) and tail suspension test (TST). Furthermore, these compounds were evaluated for their anxiolytic potential in the elevated plus maze (EPM) and light dark box (LDB) tests and anticonvulsant effects in pentylenetetrazole (PTZ)-induced seizure tests. In the EPM test, administration of these compounds led to dose-dependent increases in open arm entries and in the time spent in EPM open arms. Similar results were obtained in the LDB test, wherein compounds these caused significant increases in the number of transitions between lit and dark compartments and the time spent in the lit compartment. The anxiolytic-like effects in the EPM were not reversed by pretreatment with flumazenil, whereas PTZ and bicuculline (BIC) completely abolished the anxiolytic effects, showing the involvement of the non-benzodiazepine binding sites of GABAA receptors. All four compounds induced significantly elevated brain GABA levels, indicating the involvement of a GABAergic mechanism. Additionally, molecular docking was conducted to elucidate the mode of action for the anxiolytic and anticonvulsant effects of these derivatives. Moreover, these compounds also possess drug-like properties and excellent ADMET profiles.

journal_name

Phytochemistry

journal_title

Phytochemistry

authors

Al-Harrasi A,Khan A,Rehman NU,Al-Shidhani S,Karim N,Khan I,Halim SA,Al-Rawahi A,Hussain J,Csuk R

doi

10.1016/j.phytochem.2019.04.007

subject

Has Abstract

pub_date

2019-07-01 00:00:00

pages

58-74

eissn

0031-9422

issn

1873-3700

pii

S0031-9422(18)30823-9

journal_volume

163

pub_type

杂志文章

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Evidence for the involvement of a GABAergic mechanism in the effectiveness of natural and synthetically modified incensole derivatives in neuropharmacological disorders: A computational and pharmacological approach.