Integrating UPLC-MS/MS Bioinformatics and In Vivo Experiments Validation to Elucidate the Mechanism of Wenzi Jiedu Decoction in Suppressing Colorectal Cancer.

Objectives: We used ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), bioinformatics, and in vivo experiments to study the anti-colorectal cancer (CRC) effects of Wenzi Jiedu Decoction (WJD).

Methods: Detected the main components of WJD by UPLC-MS/MS. Obtained WJD targets and CRC targets through the open source database. Analyzed the WJD-CRC targets from a macro perspective by PPI, GO, and KEGG analyses. Validated bioinformatics findings by molecular docking and animal experiments.

Results: This study obtained 91 active compounds and 240 targets of WJD. Intersection with CRC genes (GSE32323 388 DEGs, GSE 215510 1253 DEGs), 36 WJD-CRC common targets were obtained. PPI and enrichment analyses indicated WJD exerted anti-CRC effects mainly through the chemokine signaling pathway and apoptosis. Quercetin, Luteolin, Kaempferol, Formononetin, Stigmasterol, and Hederagenin were the main compounds of WJD. CXCL8, BCL-2, BAX, BCL2L1, CASP3, AKT1, and TP53 were the core targets of WJD-CRC. Bulk molecular docking showed that core WJD compounds had good docking activity with WJD-CRC targets. Animal experiments had shown the tumor inhibition rate of the WJD group was 36.53%. WJD could regulate the ratio of CD4+, CD8+, and CD4+/CD8+, reduce the expression of CXCL8, and BCL-2, and increase the expression of BAX.

Conclusions: This study indicated that the potential mechanism of WJD in the prevention and treatment of CRC had the characteristics of the multi-target, multi-path, and multi-system mechanisms, which were mainly related to the regulation of chemokines and the promotion of apoptosis.