Experimental and computational insights into the therapeutic mechanisms of resveratrol in a Drosophila α-synuclein model of Parkinson’s disease
Abstract Parkinson’s disease (PD) is a multifactorial neurodegenerative disorder driven by genetic predisposition and environmental exposure. Given its well-documented antioxidative and neuroprotective properties, resveratrol is increasingly being considered for its potential to counteract the neuro...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-05-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-00698-9 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849325785167429632 |
|---|---|
| author | Amos Olalekan Abolaji Adeola Oluwatosin Adedara Judith Chizoba Madu Oluwabunmi Tomilola Owalude Oludare Michael Ogunyemi Damilola A. Omoboyowa Folorunsho Bright Omage Alexander J. Whitworth Michael Aschner |
| author_facet | Amos Olalekan Abolaji Adeola Oluwatosin Adedara Judith Chizoba Madu Oluwabunmi Tomilola Owalude Oludare Michael Ogunyemi Damilola A. Omoboyowa Folorunsho Bright Omage Alexander J. Whitworth Michael Aschner |
| author_sort | Amos Olalekan Abolaji |
| collection | DOAJ |
| description | Abstract Parkinson’s disease (PD) is a multifactorial neurodegenerative disorder driven by genetic predisposition and environmental exposure. Given its well-documented antioxidative and neuroprotective properties, resveratrol is increasingly being considered for its potential to counteract the neuronal damage characteristic of Parkinson’s disease. Here, we investigated the therapeutic action of resveratrol in a transgenic Drosophila melanogaster model expressing human α-synuclein (SNCA, PD flies), in combination with network pharmacology and molecular docking analyses. The PD flies were fed diet supplemented with resveratrol (15, 30, and 60 mg/kg diet, approximately 6.57, 13.14 and 26.28 mM, respectively), to evaluate lifespan. This was followed by a 21-day treatment of PD flies with similar concentrations of resveratrol in the diet to evaluate cognitive function, oxidative stress, and antioxidant biomarkers, using Levodopa (0.1 mM) as positive control. The results showed that resveratrol supplementation in the diet significantly improved lifespan, locomotor activity, acetylcholinesterase and catalase activities, and thiol content compared to untreated PD flies. Furthermore, resveratrol reduced nitric oxide (nitrite/nitrate), malondialdehyde, and total hydroperoxide levels, and enhanced cellular metabolic activity and upregulated Sod1 mRNA expression (p < 0.05). The network pharmacology and molecular docking analyses identified key molecular targets that may account for the therapeutic action of resveratrol, including B-Cell Lymphoma 2, Monoamine Oxidase (MAO); in flies, MAO-Like, Dopa Decarboxylase, Protein Kinase A and Glycogen Synthase Kinase-3 (GSK-3). Among these, MAO and GSK-3 emerged as top targets as indicated by network prominence and strong binding interactions. Additionally, the binding interaction of resveratrol to SNCA at specific sites suggests a potential role in inhibiting its aggregation, which is a hallmark of PD pathology. Quantum mechanics calculations revealed that resveratrol functions as both a proton donor and acceptor, contributing to its strong target binding interactions and antioxidant potential. Overall, resveratrol supplementation in the diet may be beneficial for PD management by modulating dopamine metabolism, apoptosis, oxidative stress, and cell survival. The study provides valuable experimental and computational insights into the underlying therapeutic mechanisms of action of resveratrol and supports its potential use in PD management. |
| format | Article |
| id | doaj-art-0e4a8cea589d4f328d5a09ecf8a8b7c0 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-0e4a8cea589d4f328d5a09ecf8a8b7c02025-08-20T03:48:19ZengNature PortfolioScientific Reports2045-23222025-05-0115112210.1038/s41598-025-00698-9Experimental and computational insights into the therapeutic mechanisms of resveratrol in a Drosophila α-synuclein model of Parkinson’s diseaseAmos Olalekan Abolaji0Adeola Oluwatosin Adedara1Judith Chizoba Madu2Oluwabunmi Tomilola Owalude3Oludare Michael Ogunyemi4Damilola A. Omoboyowa5Folorunsho Bright Omage6Alexander J. Whitworth7Michael Aschner8Drosophila Laboratory, Molecular Drug Metabolism and Toxicology Unit, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of IbadanDrosophila Laboratory, Molecular Drug Metabolism and Toxicology Unit, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of IbadanDrosophila Laboratory, Molecular Drug Metabolism and Toxicology Unit, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of IbadanDrosophila Laboratory, Molecular Drug Metabolism and Toxicology Unit, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of IbadanStructural and Computational Biology Group, Nutritional and Industrial Biochemistry Research Unit, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of IbadanDepartment of Biochemistry, Adekunle Ajasin UniversityPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa MariaMRC Mitochondrial Biology Unit, University of CambridgeDepartment of Molecular Pharmacology, Albert Einstein College of MedicineAbstract Parkinson’s disease (PD) is a multifactorial neurodegenerative disorder driven by genetic predisposition and environmental exposure. Given its well-documented antioxidative and neuroprotective properties, resveratrol is increasingly being considered for its potential to counteract the neuronal damage characteristic of Parkinson’s disease. Here, we investigated the therapeutic action of resveratrol in a transgenic Drosophila melanogaster model expressing human α-synuclein (SNCA, PD flies), in combination with network pharmacology and molecular docking analyses. The PD flies were fed diet supplemented with resveratrol (15, 30, and 60 mg/kg diet, approximately 6.57, 13.14 and 26.28 mM, respectively), to evaluate lifespan. This was followed by a 21-day treatment of PD flies with similar concentrations of resveratrol in the diet to evaluate cognitive function, oxidative stress, and antioxidant biomarkers, using Levodopa (0.1 mM) as positive control. The results showed that resveratrol supplementation in the diet significantly improved lifespan, locomotor activity, acetylcholinesterase and catalase activities, and thiol content compared to untreated PD flies. Furthermore, resveratrol reduced nitric oxide (nitrite/nitrate), malondialdehyde, and total hydroperoxide levels, and enhanced cellular metabolic activity and upregulated Sod1 mRNA expression (p < 0.05). The network pharmacology and molecular docking analyses identified key molecular targets that may account for the therapeutic action of resveratrol, including B-Cell Lymphoma 2, Monoamine Oxidase (MAO); in flies, MAO-Like, Dopa Decarboxylase, Protein Kinase A and Glycogen Synthase Kinase-3 (GSK-3). Among these, MAO and GSK-3 emerged as top targets as indicated by network prominence and strong binding interactions. Additionally, the binding interaction of resveratrol to SNCA at specific sites suggests a potential role in inhibiting its aggregation, which is a hallmark of PD pathology. Quantum mechanics calculations revealed that resveratrol functions as both a proton donor and acceptor, contributing to its strong target binding interactions and antioxidant potential. Overall, resveratrol supplementation in the diet may be beneficial for PD management by modulating dopamine metabolism, apoptosis, oxidative stress, and cell survival. The study provides valuable experimental and computational insights into the underlying therapeutic mechanisms of action of resveratrol and supports its potential use in PD management.https://doi.org/10.1038/s41598-025-00698-9α-synucleinAntioxidantParkinson’s diseaseResveratrolNetwork pharmacologyMolecular docking |
| spellingShingle | Amos Olalekan Abolaji Adeola Oluwatosin Adedara Judith Chizoba Madu Oluwabunmi Tomilola Owalude Oludare Michael Ogunyemi Damilola A. Omoboyowa Folorunsho Bright Omage Alexander J. Whitworth Michael Aschner Experimental and computational insights into the therapeutic mechanisms of resveratrol in a Drosophila α-synuclein model of Parkinson’s disease Scientific Reports α-synuclein Antioxidant Parkinson’s disease Resveratrol Network pharmacology Molecular docking |
| title | Experimental and computational insights into the therapeutic mechanisms of resveratrol in a Drosophila α-synuclein model of Parkinson’s disease |
| title_full | Experimental and computational insights into the therapeutic mechanisms of resveratrol in a Drosophila α-synuclein model of Parkinson’s disease |
| title_fullStr | Experimental and computational insights into the therapeutic mechanisms of resveratrol in a Drosophila α-synuclein model of Parkinson’s disease |
| title_full_unstemmed | Experimental and computational insights into the therapeutic mechanisms of resveratrol in a Drosophila α-synuclein model of Parkinson’s disease |
| title_short | Experimental and computational insights into the therapeutic mechanisms of resveratrol in a Drosophila α-synuclein model of Parkinson’s disease |
| title_sort | experimental and computational insights into the therapeutic mechanisms of resveratrol in a drosophila α synuclein model of parkinson s disease |
| topic | α-synuclein Antioxidant Parkinson’s disease Resveratrol Network pharmacology Molecular docking |
| url | https://doi.org/10.1038/s41598-025-00698-9 |
| work_keys_str_mv | AT amosolalekanabolaji experimentalandcomputationalinsightsintothetherapeuticmechanismsofresveratrolinadrosophilaasynucleinmodelofparkinsonsdisease AT adeolaoluwatosinadedara experimentalandcomputationalinsightsintothetherapeuticmechanismsofresveratrolinadrosophilaasynucleinmodelofparkinsonsdisease AT judithchizobamadu experimentalandcomputationalinsightsintothetherapeuticmechanismsofresveratrolinadrosophilaasynucleinmodelofparkinsonsdisease AT oluwabunmitomilolaowalude experimentalandcomputationalinsightsintothetherapeuticmechanismsofresveratrolinadrosophilaasynucleinmodelofparkinsonsdisease AT oludaremichaelogunyemi experimentalandcomputationalinsightsintothetherapeuticmechanismsofresveratrolinadrosophilaasynucleinmodelofparkinsonsdisease AT damilolaaomoboyowa experimentalandcomputationalinsightsintothetherapeuticmechanismsofresveratrolinadrosophilaasynucleinmodelofparkinsonsdisease AT folorunshobrightomage experimentalandcomputationalinsightsintothetherapeuticmechanismsofresveratrolinadrosophilaasynucleinmodelofparkinsonsdisease AT alexanderjwhitworth experimentalandcomputationalinsightsintothetherapeuticmechanismsofresveratrolinadrosophilaasynucleinmodelofparkinsonsdisease AT michaelaschner experimentalandcomputationalinsightsintothetherapeuticmechanismsofresveratrolinadrosophilaasynucleinmodelofparkinsonsdisease |