Elucidating the mechanisms underlying Taohong Siwu Decoction in preventing arteriovenous fistula failure: A comprehensive study combining network pharmacology, molecular docking, and dynamic simulation

doi:10.5246/jcps.2024.06.038

Abstract

Abstract:

Arteriovenous fistula (AVF) failure poses a significant prognostic challenge for patients undergoing hemodialysis. This study aimed to elucidate the mechanisms underlying the potential therapeutic effects of Taohong Siwu Decoction (TSD) in addressing AVF failure. A comprehensive approach integrating network pharmacology, molecular docking, and dynamic simulation was employed to validate it. The active constituents and putative targets of TSD were acquired from the Traditional Chinese Medicine Systems Pharmacology (TCMSP), Traditional Chinese Medicine Integrative Platform (TCMIP), and SwissTargetPrediction databases. Targets relevant to AVF failure were retrieved from the Online Mendelian Inheritance in Man (OMIM), DisGeNET, and GeneCards databases. The construction of the herb-ingredient-target network and protein-protein interaction (PPI) network was carried out using Cytoscape. Furthermore, we performed GO and KEGG enrichment analyses using the Metascape database. Molecular docking was executed with AutoDock, and results were visualized via PyMOL software. Additionally, molecular dynamics simulations were conducted using GROMACS. In this comprehensive analysis, we identified a total of 66 active ingredients and 769 potential targets, which subsequently led us to identify 87 targets closely associated with AVF failure. Notably, 10 key ingredients and 15 core targets were singled out. Among the pivotal constituents were gibberellin A120, gibberellin A30, kaempferol, and paeoniflorin, while core targets included TNF-α, IL-6, VEGFA and MMP9. Enrichment analyses, encompassing GO and KEGG, illuminated that TSD’s potential therapeutic effects in addressing AVF failure might hinge on the modulation of inflammation, shear stress, and extracellular matrix remodeling. Furthermore, molecular docking investigations and dynamic simulations corroborated strong binding interactions between the key active constituents and the core targets. Consequently, it is plausible that TSD may enhance AVF patency primarily by regulating processes related to inflammation, shear stress, and extracellular matrix remodeling. These findings constitute a solid molecular rationale for the application of TSD in the context of AVF failure.

Key words: Taohong Siwu Decoction, Arteriovenous fistula, Network pharmacology, Molecular docking, Molecular dynamic simulation

Supporting:

Shisheng Han, Yi Wang. Elucidating the mechanisms underlying Taohong Siwu Decoction in preventing arteriovenous fistula failure: A comprehensive study combining network pharmacology, molecular docking, and dynamic simulation[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(6): 511-524.

Figures/Tables 9

Table 1. Databases and software used in this study.

Table 2. Core targets of TSD for AVF failure.

Table 3. Core ingredients of the TSD for AVF failure.

Table 4. The binding energy of active components with core targets.

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