An integrated network pharmacology and molecular modelling study of phytoconstituents targeting Alzheimer's disease
The present study involves the use of combined network pharmacology and molecular modelling approach for identifying important phytoconstituents that could modulate the functions of multiple therapeutic targets in Alzheimer’s disease. A list of botanicals reported in the literature for their efficac...
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| Language: | English |
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Elsevier
2024-12-01
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| Series: | Medicine in Omics |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590124923000123 |
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| author | Saumya Khanna Divakar Selvaraj Mehak Tyagi Devadharshini Saravanan Jayaram |
| author_facet | Saumya Khanna Divakar Selvaraj Mehak Tyagi Devadharshini Saravanan Jayaram |
| author_sort | Saumya Khanna |
| collection | DOAJ |
| description | The present study involves the use of combined network pharmacology and molecular modelling approach for identifying important phytoconstituents that could modulate the functions of multiple therapeutic targets in Alzheimer’s disease. A list of botanicals reported in the literature for their efficacy in Alzheimer’s disease, the phytochemicals present in the botanicals were identified with the help of network pharmacology approach. The pharmacokinetic properties like blood brain barrier penetration and Lipinski’s rule of five for the selected phytoconstituents were analyzed. The major targets involved in the pathogenesis of Alzheimer’s disease were collected from the DisGeNET database. The selected proteins were subjected to topological analysis using Cytoscape software to identify the important targets in the network. The top 7 phytoconstituents and 5 proteins were subjected to molecular docking, MM-GBSA and molecular dynamics studies. A total of 15 plants and 1443 phytoconstituents were identified through a literature survey and from several databases. The pharmacokinetics study revealed that 7 phytoconstituents - glycyrrhisoflavone, eugenol, ferulic acid, methyl jasmonate, geranyl formate, formononetin, and elemicin- exhibited favourable pharmacokinetic properties. Five targets, HMOX1, CNR1, STAT3, HDAC2, and MAOB were found to be important in the network of 3300 proteins based on degree centrality and betweenness centrality. Among the seven phytoconstituents, glycyrrhisoflavone exhibited good dock scores and free energy value. Based on this, the stability of glycyrrhisoflavone with the five selected targets were analyzed using molecular dynamics study. Glycyrrhisoflavone showed good stability with most of the selected therapeutic targets. The current study reveals that the selected phytoconstituents i.e glycyrrhisoflavone, eugenol, ferulic acid, methyl jasmonate, geranyl formate, formononetin, and elemicin could serve as good lead molecules in treatment and management of Alzheimer’s disease through modulation of multiple targets. |
| format | Article |
| id | doaj-art-dc8a347ef5b946c6b469e38861e5eb7c |
| institution | OA Journals |
| issn | 2590-1249 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Medicine in Omics |
| spelling | doaj-art-dc8a347ef5b946c6b469e38861e5eb7c2025-08-20T02:18:57ZengElsevierMedicine in Omics2590-12492024-12-011210003110.1016/j.meomic.2023.100031An integrated network pharmacology and molecular modelling study of phytoconstituents targeting Alzheimer's diseaseSaumya Khanna0Divakar Selvaraj1Mehak Tyagi2 Devadharshini3Saravanan Jayaram4Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, The Nilgiris, Tamil Nadu, IndiaDepartment of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, The Nilgiris, Tamil Nadu, IndiaDepartment of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, The Nilgiris, Tamil Nadu, IndiaDepartment of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, The Nilgiris, Tamil Nadu, IndiaCorresponding author at: Department of Pharmacology, JSS College of Pharmacy, Ooty, The Nilgiris.; Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, The Nilgiris, Tamil Nadu, IndiaThe present study involves the use of combined network pharmacology and molecular modelling approach for identifying important phytoconstituents that could modulate the functions of multiple therapeutic targets in Alzheimer’s disease. A list of botanicals reported in the literature for their efficacy in Alzheimer’s disease, the phytochemicals present in the botanicals were identified with the help of network pharmacology approach. The pharmacokinetic properties like blood brain barrier penetration and Lipinski’s rule of five for the selected phytoconstituents were analyzed. The major targets involved in the pathogenesis of Alzheimer’s disease were collected from the DisGeNET database. The selected proteins were subjected to topological analysis using Cytoscape software to identify the important targets in the network. The top 7 phytoconstituents and 5 proteins were subjected to molecular docking, MM-GBSA and molecular dynamics studies. A total of 15 plants and 1443 phytoconstituents were identified through a literature survey and from several databases. The pharmacokinetics study revealed that 7 phytoconstituents - glycyrrhisoflavone, eugenol, ferulic acid, methyl jasmonate, geranyl formate, formononetin, and elemicin- exhibited favourable pharmacokinetic properties. Five targets, HMOX1, CNR1, STAT3, HDAC2, and MAOB were found to be important in the network of 3300 proteins based on degree centrality and betweenness centrality. Among the seven phytoconstituents, glycyrrhisoflavone exhibited good dock scores and free energy value. Based on this, the stability of glycyrrhisoflavone with the five selected targets were analyzed using molecular dynamics study. Glycyrrhisoflavone showed good stability with most of the selected therapeutic targets. The current study reveals that the selected phytoconstituents i.e glycyrrhisoflavone, eugenol, ferulic acid, methyl jasmonate, geranyl formate, formononetin, and elemicin could serve as good lead molecules in treatment and management of Alzheimer’s disease through modulation of multiple targets.http://www.sciencedirect.com/science/article/pii/S2590124923000123Network pharmacologyAlzheimer’s diseasePhytoconstituentsMolecular DockingMolecular Dynamics |
| spellingShingle | Saumya Khanna Divakar Selvaraj Mehak Tyagi Devadharshini Saravanan Jayaram An integrated network pharmacology and molecular modelling study of phytoconstituents targeting Alzheimer's disease Medicine in Omics Network pharmacology Alzheimer’s disease Phytoconstituents Molecular Docking Molecular Dynamics |
| title | An integrated network pharmacology and molecular modelling study of phytoconstituents targeting Alzheimer's disease |
| title_full | An integrated network pharmacology and molecular modelling study of phytoconstituents targeting Alzheimer's disease |
| title_fullStr | An integrated network pharmacology and molecular modelling study of phytoconstituents targeting Alzheimer's disease |
| title_full_unstemmed | An integrated network pharmacology and molecular modelling study of phytoconstituents targeting Alzheimer's disease |
| title_short | An integrated network pharmacology and molecular modelling study of phytoconstituents targeting Alzheimer's disease |
| title_sort | integrated network pharmacology and molecular modelling study of phytoconstituents targeting alzheimer s disease |
| topic | Network pharmacology Alzheimer’s disease Phytoconstituents Molecular Docking Molecular Dynamics |
| url | http://www.sciencedirect.com/science/article/pii/S2590124923000123 |
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