<i>Syzygium aromaticum</i> Attenuates Cerebellar Oxidative Stress: An Integrated in silico, in vitro, and in vivo Evaluation of Multi-Target Antioxidant Mechanisms.

Overview

1. Department of Anatomy, Kampala International University Western Campus, Ishaka-Bushenyi, Uganda
2. Anatomy Department, School of Medicine and Pharmacy, University of Rwanda, Butare, Rwanda
3. Department of Biochemistry, Kampala International University Western Campus, Ishaka-Bushenyi, Uganda

Abstract

Introduction: The central role of oxidative stress in neuronal injury and the progression of neurological disorders underscores the need to identify multi-target agents capable of restoring redox homeostasis. This study evaluated the antioxidant and pharmacological potential of Syzygium aromaticum ethyl acetate fraction (SEAF) using integrated phytochemical, computational, and experimental approaches.

Methods: GC-MS was used to characterize the phytochemical composition of the ethyl acetate fraction of Syzygium aromaticum (SEAF). Thirteen phytometabolites with relative peak areas ≥1.0% were selected for ADME-Tox profiling and molecular docking against monoamine oxidase B (MAO-B) and 5-lipoxygenase (5-LOX). In vitro antioxidant assays, acute oral toxicity testing, and in vivo evaluation of cerebellar oxidative stress biomarkers were subsequently performed.

Results: GC-MS identified eugenyl acetate (43.08%), eugenol (18.86%), and β-caryophyllene (1.64%) as the predominant metabolites. The prioritized phytometabolites exhibited favorable predicted ADME-Tox profiles and notable binding energies for MAO-B (up to −8.4 kcal/mol) and 5-LOX (up to −6.8 kcal/mol), involving key interactions with HIS367 and HIS372 in MAO-B and GLN363, TYR435, and CYS172 in 5-LOX, comparable to the standard ligands. Although ascorbic acid exhibited greater radical-scavenging and ferric-reducing potencies than SEAF in the DPPH and FRAP assays, respectively, SEAF showed higher total antioxidant activity than ascorbic acid. In vivo, SEAF administration was relatively safe up to 2000 mg/kg and significantly increased cerebellar superoxide dismutase and catalase activities while reducing malondialdehyde levels in HgCl2-treated mice, with effects comparable to vitamin E. SEAF preserved cerebellar cortex histoarchitecture and Nissl substance in Purkinje cells against mercuric chloride-evoked oxidative damage.

Conclusion: Syzygium aromaticum exhibited potent antioxidant effects through combined radical scavenging, enzymatic enhancement, modulation of oxidative stress-related targets, and preservation of cerebellar histoarchitecture, supporting its potential as a candidate for further preclinical development.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

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• figshare:32920373, at figshare; found in the references

Data Sharing Statement

The dataset related to this study will be available from the corresponding author upon reasonable request.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 8 authors, 5 keywords, 62 references.

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This paper

Etukudo, E. M., Usman, I. M., Oviosun, A., Ojiakor, V. O., Makena, W., Owembabazi, E., Aja, P. M., & Anyanwu, E. (2026). <i>Syzygium aromaticum</i> Attenuates Cerebellar Oxidative Stress: An Integrated in silico, in vitro, and in vivo Evaluation of Multi-Target Antioxidant Mechanisms. Journal of experimental pharmacology, 18, 630837. https://doi.org/10.2147/jep.s630837

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