Shahzadi, Z., Yousaf, Z., Anjum, I., Bilal, M., Yasin, H., Aftab, A., Booker, A., Ullah, R. and Bari, A. 2024. Network pharmacology and molecular docking: Combined computational approaches to explore the antihypertensive potential of Fabaceae species. Bioresources and Bioprocessing. 11 53. https://doi.org/10.1186/s40643-024-00764-6
| Title | Network pharmacology and molecular docking: Combined computational approaches to explore the antihypertensive potential of Fabaceae species |
|---|---|
| Type | Journal article |
| Authors | Shahzadi, Z., Yousaf, Z., Anjum, I., Bilal, M., Yasin, H., Aftab, A., Booker, A., Ullah, R. and Bari, A. |
| Abstract | Hypertension is a major global public health issue, affecting a quarter of adults worldwide and expected to increase 29% by 2025, making it a key factor in cardiovascular health. Numerous synthetic drugs are available for treating hypertension; however, they often come with a higher risk of side effects and long term therapy. While plant extract treatments face safety and dosage challenges. Modern formulations with active phytoconstituents are gaining popularity, addressing some of these issues. Therefore, this study aims to discover novel antihypertensive compounds in three species of family Fabaceae and understand their interaction mechanism with hypertension targets using network pharmacology and molecular docking. In this study, potential compounds were gathered from various sources, including published literature and databases like Google Scholar, PubMed, Phytohub, and IMPAAT. These compounds underwent initial screening through DataWarrior and SwissADME. Toxicity and bioactivity score prediction was performed by Protox-II and Molinspiration. The study then searched for common targets related to hypertension using SwissTargetPrediction, GeneCard, and DisGeNET, followed by network analysis and identification of hub genes using STRING and Cytoscape, respectively. Gene ontology and enriched pathways were explored through DAVID. Molecular docking and MD simulation was performed using AutoDock Vina and GROMACS software, respectively. Total 414 compounds were identified; initial screening was conducted based on their pharmacokinetic and ADMET properties, with a particular emphasis on adherence to Lipinski's rules. 6 compounds, namely germichrysone, benzeneacetic acid, Flavan-3-ol, 5,7,3',4'-Tetrahydroxy-6, 8-dimethoxyflavon, dihydrokaempferol, and epiafzelechin, were identified as effective agents. Most of the compounds found non-toxic against various indicators with greater bioactivity score. 161 common targets were obtained against these compounds and hypertension followed by compound-target network construction and protein-protein interaction, which showed their role in diverse biological system. Top hub genes identified were TLR4, MMP9, MAPK14, AKT1, VEGFA and HSP90AA1 with their respective associates. Higher binding affinities was found with three compounds Dihydrokaempferol, Flavan-3-ol and Germichrysone, -7.1, -9.0 and -8.0 kcal/mol, respectively. The MD simulation results validate the structural flexibility of two complexes Flavan-MMP9 and Germich-TLR4 based on no. of hydrogen bonds, root mean square deviations and interaction energies. This study concluded that family fabaceae have therapeutic potential to treat hypertension and in future novel drug formulation. |
| Keywords | Hypertension |
| herbal medicine | |
| phytochemicals | |
| Fabaceae | |
| Cassia species | |
| network pharmacology | |
| molecular docking | |
| Article number | 53 |
| Journal | Bioresources and Bioprocessing |
| Journal citation | 11 |
| ISSN | 2197-4365 |
| Year | 2024 |
| Publisher | Springer |
| Publisher's version | License CC BY 4.0 File Access Level Open (open metadata and files) |
| Digital Object Identifier (DOI) | https://doi.org/10.1186/s40643-024-00764-6 |
| PubMed ID | 38767701 |
| Publication dates | |
| Published | 20 May 2024 |