Integrative Network Pharmacology to Evaluate Bioactive Phytochemicals of Aesculus hippocastanum and Their Multitarget Mechanisms Against Chronic Venous Insufficiency
Chronic venous insufficiency (CVI) affects the venous system of the lower limbs, leading to pain, edema, skin anomalies, ulceration, and extended venous hypertension. Aesculus hippocastanum seed extract has been traditionally used for CVI treatment. This study aims to elucidate its mechanism of acti...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-01-01
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| Series: | Scientifica |
| Online Access: | http://dx.doi.org/10.1155/sci5/6871086 |
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| Summary: | Chronic venous insufficiency (CVI) affects the venous system of the lower limbs, leading to pain, edema, skin anomalies, ulceration, and extended venous hypertension. Aesculus hippocastanum seed extract has been traditionally used for CVI treatment. This study aims to elucidate its mechanism of action using in silico approaches. An integrated network pharmacology technique identified potential components for CVI treatment. From 105 chemical elements of A. hippocastanum collected via literature research, 12 active phytochemicals with notable drug-like properties and bioavailability were selected. These chemicals were linked to 213 putative target genes using the SwissTargetPrediction database. Comparison with CVI-related genes from GeneCards and OMIM databases narrowed these 147 crucial genes shared by A. hippocastanum and CVI pathophysiology. A compound-target network revealed interactions influencing CVI-related pathways. After that, protein–protein interaction analysis using STRING and Cytoscape identified key hub genes, including SRC and MAPK3, critical to CVI pathogenesis. GO and KEGG pathway analyses further highlighted biological functions and signaling pathways associated with A. hippocastanum’s anti-CVI effects. Moreover, virtual screening and molecular docking analysis demonstrated high binding affinities of alpha-spinasterol with MAPK3 (−9.3 kcal/mol) and kaempferol with SRC (−9.0 kcal/mol). Molecular dynamics simulation confirmed the binding capacity and stability of SRC–kaempferol and MAPK3–alpha-spinasterol. Ligands showed strong catalytic site binding, as evidenced by molecular mechanics–generalized born surface area (MM-GBSA) analysis. This comprehensive investigation highlights the potential therapeutic benefits of A. hippocastanum seed extract for CVI treatment and encourages further studies on its mechanism and clinical applications. |
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| ISSN: | 2090-908X |