Exploring mechanisms of britannin against colorectal cancer based on experimentally validated network pharmacology.

Abstract

Britannin is an active compound derived from Inula japonica Thunb. that possess a wide range of pharmacological activities. However, the mechanism underlying its influence on colorectal cancer (CRC) is not clear. This study aimed to explore the mechanism of britannin in treating colorectal cancer. We employed network pharmacology and single-cell RNA sequencing to assess the potential mechanism of britannin in CRC therapy. In vivo and in vitro experiments were conducted to confirm the effect of britannin on CRC cells and tumor environment. Network pharmacology analysis identified 36 britannin-related genes associated with CRC. Key signaling pathways, including the PI3K-Akt pathway, PD-L1 expression, and HIF-1 signaling, were implicated in britannin's anti-CRC effects. CIBERSORT and scRNA-seq analyses revealed that britannin affects tumor cells, macrophages, and endothelial cells, with a particular impact on macrophage polarization. In vitro assays confirmed that britannin suppressed CRC cell proliferation, promoted apoptosis, and inhibited AKT phosphorylation. In vivo, britannin significantly suppressed tumor growth and modulated the tumor microenvironment by inhibiting M1 macrophage polarization. Britannin may inhibit colorectal by directly inhibiting colon cancer cells and modulating macrophage polarization.