# Mechanisms Underlying the Cognitive Benefits of Solanum macrocarpon Leaf n-Butanol Extract: Acetylcholinesterase Inhibition and Oxidative Stress Modulation

**Authors:** Ion Brinza, Ibukun Oluwabukola Oresanya, Ilkay Erdogan Orhan, Hasya Nazlı Gök, Lucian Hritcu, Razvan Stefan Boiangiu

PMC · DOI: 10.3390/plants14213283 · 2025-10-27

## TL;DR

This study shows that an extract from Solanum macrocarpon leaves helps reduce anxiety and cognitive issues in zebrafish by improving brain function and reducing oxidative stress.

## Contribution

The study identifies acetylcholinesterase inhibition and antioxidant effects as mechanisms for the cognitive benefits of Solanum macrocarpon leaf extract.

## Key findings

- SMB reduced anxiety-like behaviors and cognitive deficits in a dose-dependent manner in zebrafish.
- SMB inhibited acetylcholinesterase activity and enhanced antioxidant enzyme activity.
- SMB lowered oxidative stress biomarkers like malondialdehyde and protein carbonyls.

## Abstract

This study investigates the neuroprotective and anxiolytic effects of Solanum macrocarpon L. leaf n-butanol extract (SMB) in a zebrafish model of scopolamine (SCOP; 100 μM)-induced cognitive and behavioral impairments. SCOP, a muscarinic receptor antagonist, is commonly used to mimic memory deficits and anxiety-like behaviors associated with neurodegenerative conditions. Zebrafish were chronically exposed to SMB at concentrations of 1, 3, and 6 mg/L. Behavioral assessments included anxiety-related paradigms, such as novel tank diving (NTT), novel approach (NA), and light–dark transition (LD) tests, as well as cognitive assays, including the Y-maze and novel object recognition (NOR) tests. SMB significantly mitigated SCOP-induced anxiety-like behaviors and cognitive deficits in a dose-dependent manner. Biochemical analyses demonstrated that SMB inhibited acetylcholinesterase (AChE) overactivity, indicating restoration of cholinergic function. Furthermore, SMB enhanced the activity of endogenous antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) and significantly reduced oxidative stress biomarkers, including malondialdehyde (MDA) and protein carbonyls. These findings suggest that SMB may exert neuroprotective effects through modulation of cholinergic signaling and oxidative stress. Overall, SMB represents a promising phytotherapeutic candidate for mitigating cognitive and anxiety-related symptoms linked to oxidative damage. Further investigations are warranted to characterize its active constituents and assess long-term efficacy and safety in models of neurodegeneration.

## Linked entities

- **Proteins:** Cat (Catalase), GPX2 (glutathione peroxidase 2)
- **Chemicals:** scopolamine (PubChem CID 5184), malondialdehyde (PubChem CID 10964)
- **Species:** Danio rerio (taxon 7955)

## Full-text entities

- **Genes:** cat (catalase) [NCBI Gene 30068] {aka fb68a12, wu:fb68a12}, ache (acetylcholinesterase (Yt blood group)) [NCBI Gene 114549] {aka zgc:92550}
- **Diseases:** memory deficits (MESH:D008569), cognitive and behavioral impairments (MESH:D003072), neurodegeneration (MESH:D019636), anxiety (MESH:D001007), cognitive and anxiety (MESH:D001008)
- **Chemicals:** SCOP (MESH:D012601), SMB (-), MDA (MESH:D008315)
- **Species:** Danio rerio (leopard danio, species) [taxon 7955]

## Figures

15 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12609031/full.md

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Source: https://tomesphere.com/paper/PMC12609031