Baicalein, a component of banxia xiexin decoction, alleviates CPT-11-induced gastrointestinal dysfunction by inhibiting ALOX15-mediated ferroptosis.

Abstract

Baicalein, one of the active ingredients of banxia xiexin decoction, has good therapeutic efficacy in treating diarrhea and improving gastrointestinal dysfunction. The role and mechanism of Baicalein on irinotecan (CPT-11)-induced gastrointestinal dysfunction are the focus of this study. Concretely, CPT-11 induced delayed diarrhea rat model and intestinal epithelial cell (IEC)-6 cell injury model with Baicalein treatment as needed. Colonic pathological changes were analyzed by hematoxylin-eosin staining, and inflammatory factor expressions in serum were determined by enzyme-linked immunosorbent assay. Immunohistochemistry and western blot were performed to quantify ferroptosis-related protein expressions. Thiobarbituric acid reactive substances (TBARS) kits and colorimetric assay kit were applied to detect lipid peroxidation levels and Fe²⁺ content, respectively. In vitro experiments also included quantitative real-time polymerase chain reaction, cell counting kit-8, and C11 BODIPY staining. CPT-11 induced aggravation of intestinal tissue damage, inflammatory factor release, Fe²⁺ accumulation, upregulation of lipid peroxidation and 15-Lipoxygenase (ALOX15) expression, and downregulation of glutathione peroxidase 4 (Gpx4) and SLC7A11 in vivo in rats; however, Baicalein dose-dependently reversed the effects of CPT-11. Baicalein elevated cell viability, reduced lipid peroxidation and Fe²⁺ accumulation, and elevated Gpx4 and SLC7A11 levels, whereas ALOX15 overexpression reversed the effects of Baicalein on a CPT-11-induced IEC-6 cell injury model. In conclusion, Baicalein plays a mitigating role in CPT-11-induced delayed diarrhea via ALOX15-mediated ferroptosis.