Exploring the Antitumor Mechanisms of Zingiberis Rhizoma Combined with Coptidis Rhizoma Using a Network Pharmacology Approach

BACKGROUND: Although the combination of Zingiberis rhizoma (ZR) and Coptidis rhizoma (CR) is a classic traditional Chinese medicine-based herbal pair used for its antitumor effect, the material basis and underlying mechanisms are unclear. Here, a network pharmacology approach was used to elucidate the antitumor mechanisms of ZR-CR. MATERIALS AND METHODS: To predict the targets of ZR-CR in treating tumors, we constructed protein–protein interactions and hub component-target networks and performed pathway and process enrichment and molecular docking analysis. We used a surface plasmon resonance (SPR) assay to validate the predicted component-target affinities. Hub gene expression and survival analysis in patients with tumors were used to predict the clinical significance. RESULTS: The active components of ZR-CR—shogaol, daucosterol, ginkgetin, berberine, quercetin, chlorogenic acid, and vanillic acid—exhibited antitumor activities via the MAPK, PI3K-AKT, TNF, FOXO, HIF-1, and VEGF signaling pathways. Molecular docking and SPR analyses suggested direct binding of berberine with AKT1 and TP53; quercetin with EGFR and VEGF165; and ginkgetin, isoginkgetin, and daucosterol with VEGF165 with weak affinities. Gene expression levels of the hub targets of ZR-CR were associated with overall survival and disease-free survival in patients with various tumor types. CONCLUSIONS: The antitumor components of the ZR-CR herbal pair and the mechanisms underlying their antitumor effects were identified. These antitumor components deserve to be explored further in experimental and clinical studies.