Shen-Ling-Bai-Zhu-San Mitigates Ulcerative Colitis by Enhancing Intestinal Barrier Integrity via the AhR-CYP1A1-NF-κB Signal Pathway

Introduction: Ulcerative Colitis (UC) represents a persistent inflammatory disorder of the colon, typically characterized by abdominal discomfort, diarrhea, and blood stools. Shen- Ling-Bai-Zhu-San (SLBZS), a traditional Chinese herbal formula, has shown clinical efficacy in alleviating symptoms such as abdominal bloating, frequent loose stools, and diarrhea. Nonetheless, the precise molecular mechanisms underlying its therapeutic effects remain largely unclear. Methods: UPLC-QE-MS combined with network pharmacology was employed to identify bioactive compounds and potential targets of SLBZS. A Dextran Sulfate Sodium (DSS)-induced colitis mouse model was used to evaluate its effects by monitoring changes in body weight, colon length, Disease Activity Index (DAI), inflammatory cytokines, oxidative stress markers, tight junction proteins, immunofluorescence, and histopathology. Molecular docking was used to predict the interaction of active compounds with UC-related targets, and Western blot analysis was performed to validate signaling pathways. Results: SLBZS markedly improved DSS-induced colitis by restoring body weight, colon length, DAI, and histology. It suppressed pro-inflammatory cytokines and oxidative markers while enhancing antioxidant defenses. Expression of Occludin and Claudin-1 was recovered. UPLCMS/ MS identified 458 constituents, and network pharmacology revealed 98 potential targets enriched in NF-κB, TNF, and HIF-1 pathways. Validation experiments demonstrated the upregulation of AhR and CYP1A1 with concomitant downregulation of NLRP3 and IL-6. Molecular docking confirmed high-affinity interactions between key compounds and UC-related targets. Discussion: These results indicate that SLBZS exerts its effects through anti-inflammatory and antioxidant mechanisms while strengthening the intestinal barrier, reflecting its multi-target therapeutic potential. Conclusions: SLBZS alleviates UC by regulating the AhR-CYP1A1-NF-κB axis, suppressing inflammation, and maintaining mucosal barrier function.