Abstract
OBJECTIVE: Irinotecan-associated diarrhea (IAD) is a severe adverse effect that limits its clinical utility in cancer therapy. Shenling Baizhu Powder (SLBZP), a traditional Chinese herbal formula, has shown potential in alleviating chemotherapy-induced gastrointestinal toxicity, but its mechanism against IAD remains unclear. This study integrated network pharmacology and experimental validation to systematically explore the therapeutic mechanisms of SLBZP in IAD. METHODS: Network pharmacology approaches were employed to identify bioactive components of SLBZP and their targets using the TCMSP database, while IAD-related targets were retrieved from Genecards. Protein-protein interaction (PPI) analysis and KEGG pathway enrichment were performed to pinpoint core targets and signaling pathways. For in vivo validation, an IAD rat model was established via tail vein injection of irinotecan (150 mg/kg), with SLBZP intervention and Gegen Qinlian Decoction (GGQLD) as a positive control. In vitro, LPS-stimulated NCM460 cells were treated with SLBZP water extract. Mechanistic evaluations were performed using molecular biology techniques, including ELISA, qPCR, and Western blotting, to validate the underlying mechanisms. RESULTS: Network pharmacology analysis revealed that SLBZP exerted therapeutic effects against IAD by closely interacting with multiple inflammatory-related targets and pathways. In vivo studies demonstrated that SLBZP significantly ameliorated diarrhea severity, improved histopathological manifestations in intestinal tissues, and suppressed the expression of key inflammatory cytokines (TNF-α, IL-6, and IL-1β). Mechanistically, SLBZP inhibited the aberrant activation of inflammatory signaling pathways, including PI3K/AKT, MAPK, and NF-κB. Consistent findings were observed in vitro, where SLBZP water extract attenuated inflammatory responses in LPS-stimulated NCM460 cells. CONCLUSION: Integrated network pharmacology analysis and experimental validation demonstrate that SLBZP alleviates IAD primarily by suppressing intestinal inflammatory responses, providing mechanistic evidence to support its clinical application in managing chemotherapy-induced intestinal toxicity.