Elucidation of significant pathways of Korean Thistle (Cirsium japonicum var. maackii (Maxim.) Matsum.) flower against cancer through network pharmacology

Cirsium japonicum var. maackii (Maxim.) Matsum., or Korean thistle flower, is a herbal plant used to treat tumor in Korean folk remedies, but its essential bioactives and pharmacological mechanisms against cancer have remained unexplored. This study identified the main compounds(s) and mechanism(s) of C. maackii flower against cancer via network pharmacology. The bioactives from C. maackii flower were revealed by gas chromatography-mass spectrum (GC-MS), and SwissADME evaluated their physicochemical properties. Target(s) associated with obtained bioactives or cancer-related targets were retrieved by public databases, and the Venn diagram selected the overlapping targets. The networks between overlapping targets and bioactives were visualized, constructed, and analyzed by RPackage. Finally, we implemented a molecular docking test (MDT) to explore key target(s) and compound(s) on AutoDockVina and LigPlot+. GC-MS detected a total of 34 bioactives and all were accepted by the Lipinski's rules and therefore decided as drug-like compounds (DLCs). A total of 597 bioactives related targets and 4,245 cancer-related targets were identified from public databases. The final 51 overlapping targets were selected between the bioactives-targets network and cancer-related targets. On Kyoto Encyclopedia of Genes and Genomes (KEGG), the number of 20 signaling pathways were manifested, and a hub signaling pathway (PI3K-Akt signaling pathway), a key target (Akt1), and a key compound (Urs-12-en-24-oic acid, 3-oxo, methyl ester) were selected among the 20 signaling pathways via MDT. Overall, Urs-12-en-24-oic acid, 3-oxo, methyl ester from C. maackii flower has potent anti-cancer efficacy by inactivating Akt1 on the PI3K-Akt signaling pathway.