Unraveling the anti-breast cancer activity of Cimicifugae rhizoma using biological network pathways and molecular dynamics simulation.

Cimicifugae is a commonly used treatment for breast cancer, but the specific molecular mechanisms underlying its effectiveness remain unclear. In this research, we employ a combination of network pharmacology, molecular docking, and molecular dynamics simulations to uncover the most potent phytochemical within Cimicifugae rhizoma in order to delve into its interaction with the target protein in breast cancer treatment. We identified 18 active compounds and 89 associated targets, primarily associated to various biological processes such as lipid metabolism, the signaling pathway in diabetes, viral infections, and cancer-related pathways. Molecular docking analysis revealed that the two most active compounds, Formononetin and Cimigenol, exhibit strong binding to the target protein AKT1. Through molecular dynamics simulations, we found that the Cimigenol-AKT1 complex exhibits greater structural stability and lower interaction energy compared to the stigmasterol-AKT1 complex. Our study demonstrates that Cimicifugae rhizoma exerts its effects in breast cancer treatment through a multi-component, multi-target synergistic approach. Furthermore, we propose that Cimigenol, targeting AKT-1, represents the most effective compound, offering valuable insights into the molecular mechanisms underpinning its role in breast cancer therapy.