Integrated network pharmacology and molecular docking approaches to reveal the synergistic mechanism of multiple components in Venenum Bufonis for ameliorating heart failure

Abstract

Venenum Bufonis (VB), also called Chan Su in China, has been extensively used as a traditional Chinese medicine (TCM) for treating heart failure (HF) since ancient time. However, the active components and the potential anti-HF mechanism of VB remain unclear. In the current study, the major absorbed components and metabolites of VB after oral administration in rats were first collected from literatures. A total of 17 prototypes and 25 metabolites were gathered. Next, a feasible network-based pharmacological approach was developed and employed to explore the therapeutic mechanism of VB on HF based on the collected constituents. In total, 158 main targets were screened out and considered as effective players in ameliorating HF. Then, the VB components–main HF putative targets–main pathways network was established, clarifying the underlying biological process of VB on HF. More importantly, the main hubs were found to be highly enriched in adrenergic signalling in cardio-myocytes. After verified by molecular docking studies, four key targets (ATP1A1, GNAS, MAPK1 and PRKCA) and three potential active leading compounds (bufotalin, cinobufaginol and 19-oxo-bufalin) were identified, which may play critical roles in cardiac muscle contraction. This study demonstrated that the integrated strategy based on network pharmacology and molecular docking was helpful to uncover the synergistic mechanism of multiple constituents in TCM.

Protective effects of agrimonolide on hypoxia‐induced H9c2 cell injury by maintaining mitochondrial homeostasis

“…It is reported that these differential genes play an important role in the process of mitochondrial damage. [34][35][36][37][38][39] For example, the expression of ndufb6 and ndufs3 increased after AF-HF001 treatment, which increased myocardial contractility and improved oxidative damage. 38 Overexpression of Uqcrh can improve mitochondrial function.…”

Study on the mechanism of Danshen-Guizhi drug pair in the treatment of ovarian cancer based on network pharmacology and in vitro experiment

“…The corresponding PDB ID of the core targets was found in the PBD ( ) database and saved as pdb format. Then the target was dehydrated and hydrogenated to optimize ligand in Pymol ( Ren et al, 2020 ). Finally, the molecular docking was performed by AutoDock software to calculate the binding ability of the main active components of the Danshen-Guizhi drug pair to the core targets.…”

Novel Strategies for Solubility and Bioavailability Enhancement of Bufadienolides

“…Ren et al [ 41 ] revealed the synergistic mechanism of multiple components in Venenum Bufonis for ameliorating heart failure by integrating network pharmacology and molecular docking approaches. Their study identified four key targets (ATP1A1, GNAS, MAPK1 and PRKCA) and three potential active leading compounds (bufotalin, cinobufaginol and 19-oxy-bufalin) that may play a key role in myocardial contraction.…”