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.

升麻是乳腺癌的常用治疗方法，但其有效性的具体分子机制仍不清楚。在这项研究中，我们结合网络药理学、分子对接和分子动力学模拟来揭示升麻中最有效的植物化学物质，以深入研究其在乳腺癌治疗中与靶蛋白的相互作用。我们鉴定了 18 种活性化合物和 89 个相关靶点，主要与脂质代谢、糖尿病信号通路、病毒感染和癌症相关通路等各种生物过程相关。分子对接分析显示，两种最活跃的化合物芒柄花素和 Cimigenol 与靶蛋白 AKT1 表现出强烈的结合。通过分子动力学模拟，我们发现与豆甾醇-AKT1复合物相比，Cimigenol-AKT1复合物表现出更高的结构稳定性和更低的相互作用能。我们的研究表明，升麻通过多成分、多靶点协同作用在乳腺癌治疗中发挥作用。此外，我们认为，针对 AKT-1 的 Cimigenol 是最有效的化合物，为了解其在乳腺癌治疗中的作用的分子机制提供了宝贵的见解。