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

ABSTRACT 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.