Integrative network pharmacology and multi-omics to investigate the potential mechanisms involved in Wumei Wan treatment of colorectal adenomas

Background Wumei Wan (WMW), a classical Traditional Chinese Medicine (TCM) formulation, has been employed for treating colorectal adenoma (CRA), yet its pharmacological mechanisms remain to be elucidated. This study investigated the protective effects of WMW on CRA through the regulation of the arachidonic acid (AA) metabolism pathway. Methods Blood components of WMW were analyzed, and network pharmacology was used to predict potential targets. The APC^min/+ mouse model was utilized to assess the effects of WMW on intestinal tumor number and size, with histopathology evaluated by H&E staining. Immunohistochemistry was employed to analyze Ki67 and p53 expression. Multi-omics approaches, including fecal metagenomics, UHPLC-Q-TOF MS, transcriptomics, and 4D-label-free proteomics, were used to study fecal microbiota, serum metabolites, colon mRNA, and protein expression. Real-time quantitative PCR (RT-qPCR) was used to verify the multi-omics findings. Results UHPLC-MS identified 809 blood components in WMW. WMW significantly reduced tumor number and size in CRA mice. Multi-omics analysis revealed WMW’s regulation of the AA metabolism pathway, identifying key metabolites (8(S)-HETE, PGF2α, and 12-HETE), genes (Cyp2e1, Pla2g2a, Pla2g4c, Alox5, Alox15, and Ptgds), and proteins (Alox15 and Pla2g4c). RT-qPCR confirmed consistent mRNA expression of Mmp9, Il-1a, Esr1, Il-13, Cyp2e1, Alox5, Alox15, Pla2g2a, Pla2g4c, and Ptgds. Conclusion WMW inhibits the development of colorectal adenoma by modulating the AA metabolism pathway, involving changes in intestinal microbiota, serum metabolites, and mRNA/protein expression in the colon.