整合转录组学及网络药理学研究仙连解毒方干预结直肠"炎-癌转化"的机制OA

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 valida‑tion 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 sig‑nificantly downregulated the expression of multiple inflammatory cytokines while upregulating tight junction-related genes in the co‑lon.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 upregu‑lated 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.