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Biomolecules
Volume 16
Issue 6
10.3390/biom16060871
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Chitosan Nanoparticles Co-Encapsulating Selegiline Analogue and L-Tyrosine Mitigate Depression-Related Pathology and Cognitive Decline in Rats

by
Wesam Abd El-Fattah
1,
Ahlem Guesmi
1,*,
Naoufel Ben Hamadi
1,
Khulud M. Alshehri
2,
Ehab Mohamed Abdella
3,4,
Rehab R. Mohamed
5,
Reda F. M. Elshaarawy
6,* and
Hani S. Hafez
7
1
Department of Chemistry, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), P.O. Box 5701, Riyadh 11623, Saudi Arabia
2
Department of Biology, Al-Baha University, Al Baha 65431, Saudi Arabia
3
Zoology Department, Faculty of Science, Beni Suef University, Beni-Suef 62521, Egypt
4
Biology Department, Faculty of Science, Al-Baha University, Al-Baha 65779, Saudi Arabia
5
Zoology Department, Science Faculty, Fayoum University, Fayoum 63514, Egypt
6
Department of Chemistry, Faculty of Science, Suez University, Suez 43533, Egypt
7
Department of Zoology, Faculty of Science, Suez University, Suez 43533, Egypt
*
Authors to whom correspondence should be addressed.
Biomolecules 2026, 16(6), 871; https://doi.org/10.3390/biom16060871 (registering DOI)
Submission received: 30 April 2026 / Revised: 4 June 2026 / Accepted: 6 June 2026 / Published: 14 June 2026
(This article belongs to the Special Issue Bionanomaterials: Synthesis, Characterization, Toxicity and Biomedical Applications, 3rd Edition)
Versions Notes

Abstract

Chronic depression is associated with oxidative stress, neuroinflammation, neurotransmitter imbalance, and Alzheimer’s-like changes. Current monoamine oxidase inhibitors have limited cognitive benefits and disease-modifying properties. A new nanotherapeutic, combining chitosan nanoparticles, propargylamino-1-(4-methylthiophenyl) propane (PAMTP), and L-tyrosine (En@PAMTP_Tyr), was developed. En@PAMTP_Tyr nanoparticles were ~140 nm in diameter, with a zeta potential of +27 mV and entrapment efficiencies of 73.45% for PAMTP and 90.85% for L-tyrosine. Drug release was pH-sensitive, favoring acidity. Intraperitoneal administration of En@PAMTP_Tyr reduced anhedonia, despair, cognitive deficits, and neuromuscular weakness, with efficacy matching or exceeding that of selegiline. In treated rats’ hippocampal tissue, En@PAMTP_Tyr increased superoxide dismutase and glutathione, normalized MAO and acetylcholinesterase activities, and corrected CUSD-induced TNF-α and IL-10 changes, showing antioxidant and anti-inflammatory effects. Histological analyses revealed that En@PAMTP_Tyr preserved CA1 pyramidal neurons, reduced β-amyloid levels, restored tau protein, and improved brain-derived neurotrophic factor levels, indicating reduced neurodegeneration. Molecular docking studies showed that PAMTP had high affinity for monoamine oxidase and acetylcholinesterase, supporting its role as an MAO-B inhibitor and cholinergic modulator. These findings suggest that En@PAMTP_Tyr is a promising nanoplatform for targeting MAO-B in depression, addressing mood, cognitive function, oxidative stress, inflammation, and Alzheimer-like pathology in the hippocampus.
Keywords: chronic unpredictable stress depression-like; cognitive dysfunction; monoamine oxidase inhibitors; oxidative stress; neuroinflammation; nano drug delivery chronic unpredictable stress depression-like; cognitive dysfunction; monoamine oxidase inhibitors; oxidative stress; neuroinflammation; nano drug delivery

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MDPI and ACS Style

Abd El-Fattah, W.; Guesmi, A.; Hamadi, N.B.; Alshehri, K.M.; Abdella, E.M.; Mohamed, R.R.; Elshaarawy, R.F.M.; Hafez, H.S. Chitosan Nanoparticles Co-Encapsulating Selegiline Analogue and L-Tyrosine Mitigate Depression-Related Pathology and Cognitive Decline in Rats. Biomolecules 2026, 16, 871. https://doi.org/10.3390/biom16060871

AMA Style

Abd El-Fattah W, Guesmi A, Hamadi NB, Alshehri KM, Abdella EM, Mohamed RR, Elshaarawy RFM, Hafez HS. Chitosan Nanoparticles Co-Encapsulating Selegiline Analogue and L-Tyrosine Mitigate Depression-Related Pathology and Cognitive Decline in Rats. Biomolecules. 2026; 16(6):871. https://doi.org/10.3390/biom16060871

Chicago/Turabian Style

Abd El-Fattah, Wesam, Ahlem Guesmi, Naoufel Ben Hamadi, Khulud M. Alshehri, Ehab Mohamed Abdella, Rehab R. Mohamed, Reda F. M. Elshaarawy, and Hani S. Hafez. 2026. "Chitosan Nanoparticles Co-Encapsulating Selegiline Analogue and L-Tyrosine Mitigate Depression-Related Pathology and Cognitive Decline in Rats" Biomolecules 16, no. 6: 871. https://doi.org/10.3390/biom16060871

APA Style

Abd El-Fattah, W., Guesmi, A., Hamadi, N. B., Alshehri, K. M., Abdella, E. M., Mohamed, R. R., Elshaarawy, R. F. M., & Hafez, H. S. (2026). Chitosan Nanoparticles Co-Encapsulating Selegiline Analogue and L-Tyrosine Mitigate Depression-Related Pathology and Cognitive Decline in Rats. Biomolecules, 16(6), 871. https://doi.org/10.3390/biom16060871

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