Qingre Huayu Jianpi prescription alleviates the inflammatory transformation of colitis-associated colorectal cancer by inhibiting the IL-17RA/ACT1/NF-κB axis.

Ethnopharmacological Relevance: Inflammation-to-cancer transformation is critical for the progression of ulcerative colitis to colitis-associated colorectal cancer (CAC).

Aim Of The Study: To explore the role and potential mechanisms of Qingre Huayu Jianpi prescription (QHJ) treatment in the development of CAC.

Materials And Methods: Combined network pharmacology and transcriptome analyses were used to investigate QHJ-associated targets and pathways in the context of CAC. Using clinical data and a murine CAC model, we examined QHJ effects on pathological morphology, inflammatory factors, and key target pathways.

Results: Network pharmacology analysis identified the interleukin 17 receptor A (IL-17RA)/ACT1/nuclear factor kappa B (NF-κB) axis as critical in the inflammation-to-CAC transformation and for QHJ effects in CAC. Western blot and multiplex immunofluorescence analyses revealed significant upregulation of the IL-17RA/ACT1/NF-κB axis along with matrix metalloproteinase (MMP)7, MMP9, and chemokine ligand 2 (CCL2) in human tumor tissues. QHJ significantly ameliorated CAC-related symptoms in mice in vivo by downregulating the IL-17RA/ACT1/NF-κB axis. This reduced the number of colorectal adenomas, increased colorectal length, and improved the structure of colonic mucosal glands. Additionally, QHJ inhibited the expression of pro-inflammatory factors and decreased the levels of MMP7, MMP9, and CCL2, ultimately suppressing the inflammation-to-cancer transformation.

Conclusion: QHJ exhibited significant therapeutic effects on CAC in mice, likely due to its inhibitory action on the IL-17RA/ACT1/NF-κB axis. This study lays the foundation for research into the pathogenesis of CAC and the clinical application of QHJ.