OBJECTIVE To investigate the therapeutic effects of Xianlian Jiedu Decoction (XLJDD) on colitis-associated colorectal cancer (CAC) and to explore its potential underlying mechanisms.
METHODS An azoxymethane/dextran sulfate sodium (AOM/DSS)-induced CAC mouse model was established. UPLC-Q-TOF/MS was employed to identify prototype compounds present in colonic tissue after XLJDD administration. Network pharmacology analysis, molecular docking, transcriptomic sequencing, and validation of key pathway-related genes were further conducted to systematically elucidate the intervention effects and potential mechanisms of XLJDD against CAC.
RESULTS In the AOM/DSS-induced CAC mouse model, XLJDD treatment markedly improved tumor-associated pathological features, as evidenced by reduced tumor burden, restored colon length, and alleviated disease activity index (DAI). UPLC-Q-TOF/MS analysis identified 22 exogenous compounds derived from XLJDD in colonic tissue. In addition, XLJDD significantly downregulated the expression of multiple inflammatory cytokines while upregulating tight junction-related genes in the colon. Transcriptomic analysis revealed that XLJDD treatment enhanced overall PPAR signaling pathway activity while suppressing the Wnt signaling pathway. Consistently, the expression levels of PPAR pathway-related genes Pparα, Cpt1a, and Ehhadh were upregulated following XLJDD intervention （P<0.05， P<0.01）, whereas the Wnt pathway-related genes Axin2 and Lef1 were significantly downregulated （P<0.05， P<0.01）.
CONCLUSION XLJDD may intervene in inflammation-associated colorectal carcinogenesis by activating the PPAR signaling pathway and suppressing the Wnt signaling pathway.
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