UPLC-QTOF-MS/MS and Bioinformatics Association Analysis Reveals the Pharmacodynamic Flavonoids in Scutellaria barbata and the Underlying Anti-Colorectal Cancer Mechanism

Colorectal Cancer (CRC) is one of the most common and deadly malignancies worldwide, with no safe and effective drugs. The flavonoid in Scutellaria Barbata D. Don (SB) showed a good therapeutic effect on CRC. However, the pharmacodynamic substances and underlying mechanisms have not been elucidated which limited its development and application. This study aimed to identify the main flavonoid in SB and explore the underlying mechanism. A total of 10 flavonoid aglycones identified by UPLC-QTOF-MS/MS were screened out as candidate compounds with good drug-likeness. By using the predicted targets of candidate compounds for CRC treatment, KEGG pathway analysis enriched 5 CRC-related pathways. Further analysis revealed that targets mapped to the five selected pathways were mainly correlated to the PI3K-Akt signaling pathway. The key targets were AKT1, VEGFA, EGFR, SRC, and MTOR. Molecular docking combined with the RNA sequencing analysis on CRC patients validated the high potential binding ability of candidate compounds to differentially expressed targets in the PI3K-Akt signaling pathway. Collectively, this study revealed that the flavonoid aglycones in SB may be the key ingredients contributing to its CRC treatment function and they exerted the CRC treatment effect by synergistic effect of multiple targets mainly belonging to the PI3K-Akt signaling pathway.