Mechanism of Artemisia argyi in the Treatment of Pancreatic Ductal Adenocarcinoma Based on Network Pharmacology and Experimental Validation.

Abstract

Introduction: Artemisia argyi (AA) demonstrates anti-cancer potential. However, its mechanisms against pancreatic ductal adenocarcinoma (PDAC) remain unclear. This study investigates the anti-tumor mechanisms of AA in PDAC.

Methods: The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to identify potential bioactive compounds. The Analyze Network tool revealed that stigmasterol (SS) was a key bioactive compound of AA. Then, the corresponding targets of SS were predicted through SwissTargetPrediction and SuperPred. A compound-target interaction network was subsequently constructed with Cytoscape, followed by the generation of a protein-protein interaction (PPI) network using the STRING database. Molecular docking was performed to evaluate the binding affinity between SS and the targets. Finally, the specific mechanism of SS on PDAC was experimentally investigated.

Results: SS was identified as a major bioactive component of AA. A total of 107 overlapping targets between SS and PDAC were collected. Molecular docking demonstrated favorable binding interactions between SS and its candidate protein targets. The experimental results suggested that SS could promote PDAC cell apoptosis through the AMPK/mTOR pathway.

Discussion: Our findings demonstrate that SS, a primary bioactive component of AA, exerts significant antitumor effects in PDAC by inducing tumor cell apoptosis through the activation of the AMPK/mTOR signaling pathway. Furthermore, we reveal a novel immunomodulatory dimension whereby SS remodels the immunosuppressive PDAC microenvironment. This dual action on both tumor cells and the immune landscape positions SS as a promising multi-faceted therapeutic candidate for PDAC.

Conclusion: SS was characterized as the key bioactive component of AA, supporting its potential role as a promising therapeutic agent for PDAC.