Immunomodulatory Mechanisms of Radix Hedysari in Colorectal Cancer via Multi-Omics Analysis 9070

Abstract Description Radix Hedysari (RH, or Hong-Qi) has long been valued for its anti-inflammatory and anti-tumor properties, yet the immunoregulatory mechanisms of its non-polysaccharide compounds in colorectal cancer (CRC) remain understudied. This study employed a multi-omics approach, integrating metabolomics, network pharmacology, proteomics, phosphoproteomics, and molecular docking, to investigate the bioactive components of RH and their impact on CRC. Advanced mass spectrometry identified 1,292 secondary metabolites in RH, including formononetin, medicarpin, naringenin, and quercetin. Network pharmacology and proteomics analyses in colon cancer cells revealed that formononetin regulates 194 targets, notably immune-related proteins carbonic anhydrase IX (CA9) and membrane metalloendopeptidase (MME). Molecular docking confirmed strong binding affinities for these targets. Pathway enrichment analyses showed significant involvement in PI3K-Akt, Hippo, HIF-1, and cholesterol metabolism signaling pathways critical to cancer immunity and immune cell activity, including tumor-associated macrophages, T regulatory cells, and cytotoxic T lymphocytes. These findings indicate that RH and formononetin modulate tumor growth and the tumor-immune microenvironment by targeting key immune signaling pathways, offering insights into RH’s mechanisms and its potential as a foundation for CRC immunotherapy. Funding Sources “Five-Level Progressive” Talent Cultivation Project of Jiangxi Cancer Hospital & Institute (No. WCDJ2024JQ02) Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)