Multi-Targeted Anti-Cancer Mechanisms of Li-Ginseng Powder in Colitis-Associated Colorectal Cancer: Integrating Inflammation, Apoptosis and Immunity

The incidence of colitis-associated colorectal cancer (CAC) is increasing, while conventional single-target therapies often demonstrate limited efficacy and long-term adverse effects. As a result, multi-target natural compounds have emerged as promising alternatives. This study investigates the anti-CAC potential of Li-Ginseng Powder (LGP), a specially processed functional food derived from Panax ginseng and enriched with rare ginsenosides (Rk1, Rk3, Rh4, Rg3, and Rg5), demonstrates strong preventive potential and characterized by minimal toxicity. Multi-omics analyses revealed that CAC model mice exhibited key tumor-promoting features, including heightened inflammation, impaired apoptosis, and immune suppression. Notably, LGP displayed significant anti-CAC activity and reversed 98.14% of dysregulated protein expression (fold-change > 1.5, p  < 0.05). It effectively mitigated inflammation by inhibiting STAT3/NF-κB signaling and modulating inflammatory gene expression. LGP induced apoptosis by downregulating anti-apoptotic proteins (Bcl-2, Bcl-XL, and x-IAP), upregulating pro-apoptotic Bax and Granzyme B, and promoting PARP and Caspase-9 cleavage to facilitate the elimination of damaged cells. Moreover, it enhanced immune responses by increasing NK cell and CD3 + T cell infiltration while activating CD4 + and CD8 + T cells. Additionally, LGP modulated serum metabolites and gut microbiota composition, fostering a favorable disease trajectory. These findings elucidate LGP’s comprehensive anti-CAC mechanism, integrating inflammation suppression, apoptosis induction, immune modulation, and microbiota regulation. This study addresses a critical gap in ginseng-derived CAC therapies, offering a promising multi-targeted and low-risk therapeutic strategy for clinical application.