Abstract

Ethnopharmacological relevance Colorectal cancer(CRC) is one of the most common malignant tumors of the digestive system, and Traditional Chinese Medicine has shown good efficacy in its treatment and prognosis. Wumei Wan(WMW) is widely used in the treatment of digestive system and tumor diseases, with effects such as anti-diarrheal, anti-dysentery, and pain relief. Modern pharmacological studies suggest that its active ingredients have anti-inflammatory, antioxidant, and anti-tumor properties. However, there is still a lack of systematic research on the role of WMW in the prevention and treatment of CRC and its molecular mechanisms. Aim of this study The aim of this study is to clarify the key active components and primary mechanisms by which WMW inhibits the initiation and progression of CRC, utilizing a multi-faceted approach including chemical composition analysis, network pharmacology, multi-omics studies, molecular biology validation, and molecular simulations. Methods UHPLC-HRMS/MS was used to identify the chemical components in WMW decoction and post-administration serum, and network pharmacology analysis was combined to predict potential targets and signaling pathways. Key differential pathways were selected through combined transcriptomics and proteomics analysis, and the expression patterns of the FAK/Src/YAP axis in CRC were verified using the GEO database. An azoxymethane/dextran sulfate sodium (AOM/DSS)-induced CRC mouse model was constructed to assess the effects of WMW on survival rate, tumor burden, histological changes in the colon, and the expression of related proteins. The expression of downstream genes CTGF and Axin2 was detected via qRT-PCR, and the regulatory effects of WMW-containing serum on FAK/Src/YAP signaling were examined in the HCT116 cells model. Finally, molecular docking and molecular dynamics simulations were performed. Results UHPLC-HRMS/MS analysis identified 15 circulating components of WMW following administration. Network pha