Meng Wang1, Youke Qi2, Yongning Sun1,2. 1. Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. 2. Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China.
Abstract
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.
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.
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