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article · Journal of Experimental Pharmacology

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

In plain language

An ethyl acetate fraction of Syzygium aromaticum was evaluated for its antioxidant properties and protective effects against cerebellar oxidative stress. Gas chromatography-mass spectrometry identified eugenyl acetate, eugenol, and beta-caryophyllene as the primary chemical constituents. Computational screening indicated that these phytometabolites have favourable predicted pharmacokinetic profiles and bind effectively to monoamine oxidase B and 5-lipoxygenase enzymes. Laboratory testing confirmed high total antioxidant activity exceeding that of ascorbic acid. In animal trials, oral administration was safe up to 2000 mg/kg and significantly improved cerebellar antioxidant enzyme levels while decreasing malondialdehyde in mice exposed to mercuric chloride. The extract performed comparably to vitamin E, successfully preserving cerebellar tissue structure and Purkinje cell integrity against heavy-metal-induced oxidative injury.

Key takeaways

  • Chemical analysis showed eugenyl acetate, eugenol, and beta-caryophyllene are the main constituents in the Syzygium aromaticum fraction.
  • Computational modelling revealed favourable binding of key metabolites to monoamine oxidase B and 5-lipoxygenase targets.
  • The extract was safe up to 2000 mg/kg in mice and matched vitamin E in lowering malondialdehyde and boosting antioxidant enzymes.
  • Administration of the extract preserved cerebellar cortex histoarchitecture and Purkinje cell integrity against mercuric chloride damage.

Why it matters

Oxidative stress plays a central role in neuronal damage and the progression of neurological disorders. Identifying safe, plant-derived multi-target agents that restore natural antioxidant defences could provide new ways to prevent or treat brain injury. This research demonstrates that Syzygium aromaticum components can shield delicate cerebellar structures and Purkinje cells from chemical-induced oxidative harm.

Commercialisation angle

This research could inform the development of botanical neuroprotective therapeutics or nutraceutical formulations targeting oxidative brain damage. Potential users include pharmaceutical developers and natural health product manufacturers exploring multi-target antioxidant candidates. The findings remain at an early preclinical stage, having only been tested through computational methods, laboratory assays, and rodent models, meaning considerable preclinical refinement and clinical trials will be necessary before any real-world application.

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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 HgCl 2 -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. Keywords: antioxidants, cerebellum, oxidative stress, phytomedicine, Syzygium aromaticum

Research topics

  • Phytochemicals and Antioxidant Activities
  • Computational Drug Discovery Methods
  • Ginger and Zingiberaceae research

Sustainable Development Goals

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DOI: 10.2147/jep.s630837

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