Exploring the Therapeutic Potential of Evodia rutaecarpa in Early-Onset Pancreatic Cancer: A Network Pharmacology and Molecular Docking Approach.

Abstract

Introduction: Pancreatic cancer (PC) remains a formidable challenge in cancer, which requires innovative approaches to identify novel therapeutic strategies. Evodia rutaecarpa, a traditional herbal remedy known for its analgesic and antiemetic properties, has been reported to exhibit anticancer effects.

Method: We employed network pharmacology to elucidate the bioactive ingredients of Evodia rutaecarpa and their potential targets in the context of early-onset pancreatic cancer. By integrating data from public databases, we identified genes associated with PC and developed a protein-protein interaction (PPI) network. Topological analysis of the PPI network facilitated the identification of core targets, which were subsequently subjected to molecular docking with corresponding bioactive ingredients of Evodia rutaecarpa. The computational approach aimed to unveil the pharmacological mechanisms of basic putative crucial proteins and associated pathways implicated in early-onset PC. Pathway and GO analysis highlighted the significant involvement of Evodia rutaecarpa in pathways such as cAMP signaling, cytokine-cytokine receptor interaction, rheumatoid arthritis, interleukin signaling, bladder cancer, IL-17, IL-24 signaling, cytokine-mediated signaling, chemokine, and calcium-mediated signaling.

Results: Further exploration focused on a hub protein module derived from PPIs, with molecular docking emphasizing strong binding interactions between Evodia rutaecarpa and ERBB2, a protein strongly implicated in PC management compared to other identified hub proteins (STAT1, ERBB2, CXCL10, INS, RACK1, FOS, HLA-DRB1, POMC, PRKAA1). Additionally, the pharmacokinetic analysis of Evodia rutaecarpa indicated its efficacy as a therapeutic agent with minimal adverse effects. Rutaecarpine, identified as the main bioactive ingredient, emerged as a potential inhibitor of PC growth through the suppression of ERBB2.

Conclusion: These outcomes provide novel insights into the prevention and treatment of PC, presenting Evodia rutaecarpa as a promising candidate for further experimental validation and clinical exploration. The identified discovery has the potential to reduce the drug resistance of Evodia rutaecarpa by engaging with a new target in a specific manner, thus improving therapeutic effectiveness.