Solanum macrocarpon L. Ethanolic Leaf Extract Exhibits Neuroprotective and Anxiolytic Effects in Scopolamine-Induced Amnesic Zebrafish Model
Abstract
1. Introduction
2. Results
2.1. Chemical Composition of SMEE
2.2. Evaluation of the Pharmacological Properties
2.3. In Silico Prediction of Biological Activity of SMEE Compounds
2.4. Safety Assessment of Chronic Exposure to SMEE
2.5. Effects on Anxiety-like Behavior in NTT, NAT, and LDT
2.6. Effects on Spatial Memory in Y-Maze
2.7. Effects on Recognition Memory in NOR
2.8. Effects on the Brain AChE Activity
2.9. Effects on Brain Oxidative Status
2.10. Pearson Correlations Between Behavioral and Biochemical Variables
3. Discussion
4. Materials and Methods
4.1. Plant Material and Extraction
4.2. High-Performance Liquid Chromatograph (HPLC-PDA)
4.3. Computational Estimation of the Pharmacokinetic Profile
4.4. Prediction of Biological Activity and Protein Target Identification
4.5. Study Design and Animal Care
4.6. Behavioral Tasks
4.6.1. Novel Tank Diving Test (NTT)
4.6.2. Novel Approach Test (NAT)
4.6.3. Light–Dark Test (LDT)
4.6.4. Y-Maze
4.6.5. Novel Object Recognition (NOR)
4.7. Biochemical Parameter Testing
4.7.1. Determining Acetylcholinesterase (AChE) Activity
4.7.2. Determining Superoxide Dismutase (SOD) Activity
4.7.3. Determining Catalase (CAT) Activity
4.7.4. Determining Glutathione Peroxidase (GPX) Activity
4.7.5. Determining Carbonylated Protein Contents
4.7.6. Malondialdehyde (MDA) Level
4.8. Data Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Sample | Compounds | Retention Time (min) | Maximum Absorbance (nm) | Amount (mg/g, Mean ± SD) | Standard Curve | R2 |
---|---|---|---|---|---|---|
SMEE | Chlorogenic acid | 15.595 | 320 | 25.46 ± 0.10 | y = 28.919x + 54.92 | 0.9974 |
Rutin | 30.000 | 260 | 7.55 ± 0.10 | y = 36.127x + 150.42 | 0.9993 |
Property | Compound Model Name | SCO | GAL | Chlorogenic Acid | Rutin | Unit |
---|---|---|---|---|---|---|
Absorption | Intestinal absorption (human) (low < 30%, high > 30%) | 72.626 | 94.994 | 36.377 | 23.446 | Numeric (% Absorbed) |
Skin permeability (low logKp > −2.5, high logKp < −2.5) | −4.097 | −3.75 | −2.735 | −2.735 | Numeric (log Kp) | |
P-glycoprotein substrate | Yes | No | Yes | Yes | Categorical (Yes/No) | |
P-glycoprotein I inhibitor | No | No | No | No | Categorical (Yes/No) | |
P-glycoprotein II inhibitor | No | No | No | No | Categorical (Yes/No) | |
Distribution | VDss (human) (low log VDss < −0.15, high VDss > 0.45) | 0.583 | 0.89 | 0.581 | 1.633 | Numeric (log L/kg) |
Unbound fraction (human) | 0.414 | 0.36 | 0.658 | 0.187 | Numeric (Fu) | |
BBB permeability (log BB > 0.3 cross BB, log BB < 0.1 do not cross BB) | −0.043 | 0.081 | −1.407 | −1.899 | Numeric (BB log) | |
CNS permeability (log PS > −2 penetrates CNS, log PS < −3 does not penetrate) | −3.031 | −2.511 | −3.856 | −5.178 | Numeric (PS log) | |
Metabolism | CYP3A4 substrate | Yes | Yes | No | No | Categorical (Yes/No) |
CYP1A2 inhibitor | No | No | No | No | Categorical (Yes/No) | |
Excretion | Total clearance | 1.096 | 0.991 | 0.307 | −0.369 | Numeric (log mL/min/kg) |
Renal OCT2 substrate | No | Yes | No | No | Categorical (Yes/No) | |
Toxicity | hERG blockers | 0.19 | 0.458 | 0.025 | 0.008 | Numeric |
hERG blockers (10 µm) | 0.418 | 0.625 | 0.093 | 0.263 | Numeric | |
DILI | 0.104 | 0.215 | 0.291 | 0.937 | Numeric | |
AMES toxicity | 0.158 | 0.559 | 0.386 | 0.756 | Numeric | |
Carcinogenicity | 0.015 | 0.726 | 0.225 | 0.047 | Numeric | |
Human hepatotoxicity | 0.895 | 0.795 | 0.543 | 0.406 | Numeric | |
Drug-induced nephrotoxicity | 0.403 | 0.802 | 0.441 | 0.148 | Numeric | |
Drug-induced neurotoxicity | 0.753 | 0.744 | 0.009 | 0.0 | Numeric | |
Hematotoxicity | 0.16 | 0.505 | 0.028 | 0.023 | Numeric | |
Genotoxicity | 0.677 | 0.739 | 0.243 | 0.868 | Numeric | |
RPMI-8226 immunotoxicity | 0.043 | 0.097 | 0.016 | 0.098 | Numeric | |
A549 cytotoxicity | 0.058 | 0.069 | 0.203 | 0.86 | Numeric |
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Brinza, I.; Guliev, C.; Oresanya, I.O.; Gok, H.N.; Orhan, I.E.; Hritcu, L. Solanum macrocarpon L. Ethanolic Leaf Extract Exhibits Neuroprotective and Anxiolytic Effects in Scopolamine-Induced Amnesic Zebrafish Model. Pharmaceuticals 2025, 18, 706. https://doi.org/10.3390/ph18050706
Brinza I, Guliev C, Oresanya IO, Gok HN, Orhan IE, Hritcu L. Solanum macrocarpon L. Ethanolic Leaf Extract Exhibits Neuroprotective and Anxiolytic Effects in Scopolamine-Induced Amnesic Zebrafish Model. Pharmaceuticals. 2025; 18(5):706. https://doi.org/10.3390/ph18050706
Chicago/Turabian StyleBrinza, Ion, Corina Guliev, Ibukun Oluwabukola Oresanya, Hasya Nazli Gok, Ilkay Erdogan Orhan, and Lucian Hritcu. 2025. "Solanum macrocarpon L. Ethanolic Leaf Extract Exhibits Neuroprotective and Anxiolytic Effects in Scopolamine-Induced Amnesic Zebrafish Model" Pharmaceuticals 18, no. 5: 706. https://doi.org/10.3390/ph18050706
APA StyleBrinza, I., Guliev, C., Oresanya, I. O., Gok, H. N., Orhan, I. E., & Hritcu, L. (2025). Solanum macrocarpon L. Ethanolic Leaf Extract Exhibits Neuroprotective and Anxiolytic Effects in Scopolamine-Induced Amnesic Zebrafish Model. Pharmaceuticals, 18(5), 706. https://doi.org/10.3390/ph18050706