Unraveling the Role of Scutellaria baicalensis for the Treatment of Breast Cancer Using Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation

Abstract

Scutellaria baicalensis is often used to treat breast cancer, but the molecular mechanism behind the action is unclear. In this study, network pharmacology, molecular docking, and molecular dynamics simulation are combined to reveal the most active compound in Scutellaria baicalensis and to explore the interaction between the compound molecule and the target protein in the treatment of breast cancer. In total, 25 active compounds and 91 targets were screened out, mainly enriched in lipids in atherosclerosis, the AGE–RAGE signal pathway of diabetes complications, human cytomegalovirus infection, Kaposi-sarcoma-associated herpesvirus infection, the IL-17 signaling pathway, small-cell lung cancer, measles, proteoglycans in cancer, human immunodeficiency virus 1 infection, and hepatitis B. Molecular docking shows that the two most active compounds, i.e., stigmasterol and coptisine, could bind well to the target AKT1. According to the MD simulations, the coptisine–AKT1 complex shows higher conformational stability and lower interaction energy than the stigmasterol–AKT1 complex. On the one hand, our study demonstrates that Scutellaria baicalensis has the characteristics of multicomponent and multitarget synergistic effects in the treatment of breast cancer. On the other hand, we suggest that the best effective compound is coptisine targeting AKT1, which can provide a theoretical basis for the further study of the drug-like active compounds and offer molecular mechanisms behind their roles in the treatment of breast cancer.

<italic>Xianling Lianxia</italic> formula enhances the inhibitory effects of trastuzumab on HER2-positive breast cancer

“…By integrating multiomics data and network analysis, researchers can identify crucial molecular pathways and key nodes involved in BC development. This knowledge provides valuable insights into the underlying mechanisms of the disease and facilitates the discovery of novel therapeutic strategies [18] . In this study, we explored the potential target of XLLXF to inhibit HER2-positive BC by network pharmacology.…”

The Mechanism of Mori Folium and Eucommiae Cortex against Cyclophosphamide-Induced Immunosuppression Integrating Network Pharmacology, Molecular Docking, Molecular Dynamics Simulations, and Experimental Validation

“…Due to the complex components of TCM and the various biological systems in which they are involved, elucidating its mechanism of action has become a challenge [12,16]. Network pharmacology takes the main active ingredients and target proteins of TCM as nodes and uses edges to represent their interactions by generating an interaction network in order to elucidate the mechanism of action of TCM prescriptions at the molecular level [17].…”

Network Pharmacology, Molecular Docking and Molecular Dynamics to Explore the Potential Immunomodulatory Mechanisms of Deer Antler

“…The targets with topology parameters above the median for all three parameters were selected to build subnetworks. This is considered acceptable in core target screening [ 60 , 61 ]. Meanwhile, in cytohubba of Cytoscape, we used the Degree, Maximum Neighborhood Component (MNC), Maximal Clique Centrality (MCC), and Closeness to obtain the top 10 targets.…”