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. 2025 May;398(5):5757-5771.
doi: 10.1007/s00210-024-03665-9. Epub 2024 Nov 28.

Unveiling the anxiolytic and analgesic effects of citronellal in Swiss mice: in vivo and in silico insights into COX and GABAA receptor pathways

Muhammad Torequl Islam  1   2   3 , Md Sakib Al Hasan  4   5 , Raihan Chowdhury  4   5 , Emon Mia  4   5 , Imam Hossen Rakib  4   5 , Noshin Tasnim Yana  4   5 , Heba A S El-Nashar  6 , Siddique Akber Ansari  7 , Irfan Aamer Ansari  8 , Md Amirul Islam  9   10 , Zainab M Almarhoon  11 , William N Setzer  12   13 , Javad Sharifi-Rad  14   15   16
Affiliations

Unveiling the anxiolytic and analgesic effects of citronellal in Swiss mice: in vivo and in silico insights into COX and GABAA receptor pathways

Muhammad Torequl Islam et al. Naunyn Schmiedebergs Arch Pharmacol. 2025 May.

Abstract

This study aims to evaluate the analgesic and anxiolytic effects of citronellal (CTL) in Swiss mice using two new sensitive and economic mouse models along with possible molecular mechanisms through in silico studies. For this, we employed marble displacement and spiked-field apparatus to check the anxiolytic and analgesic effects, respectively. In silico studies were done against cyclooxygenase (COX) enzymes and GABAA receptor subunits. Findings suggest that the test sample CTL significantly reduced the number of marbles displaces (NMD), square crosses (NSC), paw massages (NPM), and escaping attempts (NEA) in animals than the control group. CTL exhibited better effects in the perforated-field study compared to the reference drug diclofenac sodium. In both cases, CTL (200 mg/kg) significantly reduced the test parameters when combined with the standard drugs (diazepam or diclofenac sodium). In in silico studies, CTL showed binding affinities of - 5.5, - 5.2, - 4.8, and - 4.8 kcal/mol with the COX1, COX2, and GABAA receptors (α2 and α3 subunits), respectively. Taken together, CTL may exert anxiolytic- analgesic-like effects on mice, possibly through the GABAA receptor and COXs interaction pathways. These new tools might be used to check the anxiolytic and analgesic properties of a wide variety of test substances.

Keywords: Anxiety; Bioactive compound; Marble displacement; Pain; Spiked-field.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was approved by the Animal Ethics Committee of Khulna University (KUAEC-2023–05-09). No anesthetic or surgical procedures were used for this study. We checked only the behavioral parameters after the treatment; therefore, this study did not require any medication to overcome or reduce the suffering of the experimental animals. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

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