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.