Salacia fruticosa methanol extract pretreatment attenuates scopolamine-induced cognitive decline and Alzheimer's disease-related pathology in zebrafish

Abstract

Objective: To examine the effect of the methanolic extract of Salada fruticosa in a zebrafish model of scopolamine-induced Alzheimer’s disease.

Methods: High-resolution liquid chromatography-mass spectrometry was used to characterize the phytochemical constituents of Salada fruticosa methanolic extract. The drug-likeness of these compounds was determined via the DruLiTo tool, and their acetylcholinesterase (AChE) binding affinities were studied by molecular docking. In in vivo studies, adult zebrafish were treated with 3.125, 6.25, and 12.5 mg/L of the extract for seven days and then immersed in scopolamine (100 μM/L) to induce cognitive deficits. T-maze and novel object recognition tests were used for behavioral studies. In addition, the activities of AChE, antioxidant enzymes, and myeloperoxidase were determined in brain tissue of zebrafish.

Results: High-resolution liquid chromatography-mass spectrometry revealed that 40 phytoconstituents were present in the methanolic extract of Salacia fruticosa, and 27 compounds met Lipinski's rule of five, indicating good drug-likeness. Some compounds such as stylopine, p-coumaroylagmatine, and (-)-heliannuol E, demonstrated high AChE binding affinity. Moreover, pretreatment with the extract significantly mitigated zebrafish cognitive decline, as indicated by increased time spent at the novel object in novel object recognition test, as well as increased time spent and decreased latency in the green arm (P < 0.001). The extract also markedly lowered malondialdehyde and myeloperoxidase levels and AChE activity, and enhanced glutathione peroxidase and superoxide dismutase activities (P < 0.001) in zebrafish with scopolamine-induced Alzheimer’s disease. Histopathological studies revealed that Salacia fruticosa extract ameliorated scopolamine-induced abnormalities in neuronal cell morphology.

Conclusions: Pretreatment with the methanolic extract of Salacia fruticosa reduces cognitive impairment, enhances antioxidants, and attenuates oxidative stress, highlighting its potential as a preventive agent for Alzheimer’s disease.

Keywords

Scopolamine / Acetylcholinesterase inhibitors / Salacia fruticosa / Zebrafish / Molecular docking / Antioxidation / Neuroinflammation

Conflict of interest statement

The authors declare no conflict of interest.

Acknowledgments

The authors extend their appreciation to the Researchers Supporting Project Number (RSPD2025R709), King Saud University, Riyadh, Saudi Arabia for funding this study. The authors are thankful to the DST-FIST Raghavendra Institute of Pharmaceutical Education and Research for their instrumental support.

Funding

This research was funded by King Saud University, Riyadh, Saudi Arabia, Project Number (RSPD2025R709).

Data availability statement

The data supporting the findings of this study are available from the corresponding authors upon request.

Authors’ contributions

PP was responsible for the conceptualization of the study, supervision, design of the animal investigation, and manuscript editing. DP contributed to the computational studies. SP was involved in data acquisition. VM and SB were involved in writing the original manuscript. SA and HM were involved in securing the financial support required for the study.

Publisher’s note

The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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