Anxiogenic-like effects of coumarin, possibly through the GABAkine interaction pathway: Animal studies with in silico approaches.

Autor: Prottay AAS; Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh; Bioinformatics and Drug Innovation Laboratory, BioLuster Research Center Ltd., Gopalganj 8100, Bangladesh., Emamuzzaman; Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh; Bioinformatics and Drug Innovation Laboratory, BioLuster Research Center Ltd., Gopalganj 8100, Bangladesh., Ripu TR; Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh., Sarwar MN; Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh., Rahman T; Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh., Ahmmed MS; Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh., Bappi MH; School of Pharmacy, Jeonbuk National University, Jeonju 54896, Republic of Korea., Emon M; Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh., Ansari SA; Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia., Coutinho HDM; Department of Biological Chemistry, Regional University of Cariri, Crato 63105-000, Brazil. Electronic address: hdmcoutinho@gmail.com., Islam MT; Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh; Bioinformatics and Drug Innovation Laboratory, BioLuster Research Center Ltd., Gopalganj 8100, Bangladesh; Pharmacy Discipline, Khulna University, Khulna 9208, Bangladesh. Electronic address: dmt.islam@bsmrstu.edu.bd.
Jazyk: angličtina
Zdroj: Behavioural brain research [Behav Brain Res] 2024 Dec 10; Vol. 480, pp. 115392. Date of Electronic Publication: 2024 Dec 10.
DOI: 10.1016/j.bbr.2024.115392
Abstrakt: Background: Anxiety disorder is the most common mental illness and a major contributor to impairment. Thus, there is an urgent need to find novel lead compounds to mitigate anxiety. It is widely recognized that the neurobiology of anxiety-related behavior involves GABAergic systems.
Objectives: This research aimed to examine the anxiogenic action of coumarin (CMN), a natural benzopyrone derived from plants, and determine its underlying mechanism through in vivo and in silico investigations.
Methods: This was accomplished by using a variety of behavioral procedures, including open field, swing, hole cross, and light-dark tests, on male and female Swiss albino mice that had been orally administered three experimental doses of CMN (1, 2, and 4 mg/kg). The CMN group was also examined with the GABA A receptor agonist diazepam (DZP, 2 mg/kg) and flumazenil antagonist (FLU, 0.1 mg/kg). Furthermore, CMN and standards were subjected to a molecular docking analysis to determine their binding affinities for the GABA A receptor subunits (α1, α4, β2, γ2, and δ). Several software programs were used to visualize the ligand-receptor interaction and analyze the pharmacokinetic profile.
Results: Compared to typical treatments, our results show that CMN (1 mg/kg) significantly (p < 0.05) increases the locomotor activity of animals. Furthermore, CMN exerted the highest binding affinity (-6.5 kcal/mol) with the GABA-α1 receptor compared to conventional DZP. Along with FLU, CMN displayed several hydrophobic and hydrogen bonds with GABA A receptor subunits. The pharmacokinetic and drug-like properties of CMN are also remarkable. In animal studies, CMN worked synergistically with FLU to provide anxiogenic-like effects.
Conclusion: We conclude that, based on in vivo and in silico data, CMN, alone or in combination with FLU, may be employed in future neurological clinical studies. However, further research is needed to confirm this behavioral activity and elucidate the possible mechanism of action.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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