Multi-Omics and Molecular Dynamics Simulation Reveal the Therapeutic Mechanisms of <em>Cordyceps sinensis</em> against Colorectal Cancer

Introduction: Colorectal cancer is a prevalent malignancy, and Cordyceps sinensis, a traditional Chinese medicine, is reported to have therapeutic potential. However, the specific active compounds and their underlying molecular mechanisms remain to be fully understood. The objective of this study aimed to explore the potential mechanisms of Cordyceps sinensis against colorectal cancer by combining network pharmacology, molecular docking, and molecular dynamics simulations. Method: We used an integrative approach of network pharmacology, molecular docking, and molecular dynamics simulations. Through these methods, we identified the major active compounds and their core target proteins, performed GO and KEGG enrichment analyses, and evaluated the predicted binding interactions and complex stability between the active compounds and key targets. Results: We identified five major active compounds: arachidonic acid, cerevisterol, linoleyl acetate, cholesterol, and cholesteryl palmitate. The core targets of these compounds included SRC, PIK3CA, PIK3CB, PTPN11, JAK2, and PTGS2. The compounds exhibited different predicted binding interactions to these targets, with cholesterol forming the most stable complex to the core target SRC. In contrast, cerevisterol binding was associated with greater protein flexibility. Conclusions: This study provides initial computational evidence that the therapeutic mechanisms of Cordyceps sinensis against colorectal cancer are mediated by its active compounds, particularly cholesterol, which forms a stable complex with the SRC protein. This integrative multi-omics approach offers valuable scientific evidence for the pharmacological actions of Cordyceps sinensis and underscores its potential for further drug development.