Anemoside B4 alleviates colitis-associated colon cancer progression via Wnt/β-catenin signaling pathway

Colitis-associated cancer (CAC) is a subtype of colorectal cancer (CRC). The persistent inflammatory stimulation caused by ulcerative colitis (UC) can worsen intestinal damage and promote the development of cancer. Anemoside B4 (B4), an active component of Pulsatilla chinensis, has previously been shown to have beneficial effects against UC, which sets the stage for investigating its potential in preventing and treating CAC. Therefore, we explored the mechanism of B4 in the treatment of CAC based on RNA sequencing (RNA-seq). The results demonstrated that B4 treatment significantly improved weight loss, inhibited colon shortening, reduced both the number and size of tumors, alleviated colon tissue damage, and lowered mRNA levels of IL-1β, IL-6, and TNF-α in CAC mice. RNA-seq revealed that B4 can regulate the expression of key genes in the Wnt/β-catenin signaling pathway, thereby interfering with the development and progression of CAC. Molecular docking predicted that B4 binds to key targets with a high affinity, specifically Wnt6, Ctnnb1, and Ccnd1. And these findings were verified by RT-qPCR and Western blot analysis. Overall, B4 can alleviate the occurrence and development of colitis associated cancer via inhibiting the activity of the Wnt/β-catenin signaling pathway.