Decoding the healing secrets of Gegenqinlian decoction: A promising approach to radiation-induced intestinal injury

ETHNOPHARMACOLOGICAL RELEVANCE: Gegenqinlian Decoction (GQD), a Traditional Chinese Medicine formula comprising Pueraria lobata(Willd.)Ohwi, Scutellaria baicalensis Georgi, Coptis teeta Wall. and Glycyrrhiza uralensis Fisch., is utilized for damp-heat diarrhea; yet its efficacy and mechanisms in radiation-induced intestinal injury (RII) remain unclear. AIM OF THE STUDY: This study focused on investigating the therapeutic effects of GQD against RII and exploring the mechanisms of its core active components. MATERIALS AND METHODS: The mice or cells were subjected to X-ray irradiation for model establishment. The intestinal injury was assessed by H&E staining, biochemical indicators detection and TUNEL staining assay. The core active components were screened by integration of UPLC-Q-TOF-MS and network pharmacology analysis. Potential biological process, cellular component, molecular function, and pathway were predicted through Metascape. The protein expression of key pathways (NF-κB, Caspase-9/-3, Wnt/β-catenin) were evaluated by western blotting. RESULTS: GQD exhibited remarkable protective effects against RII both in vivo and in vitro. GQD improved villus length, increased crypt number, reduced inflammation and enhanced the antioxidant capacity of irradiated mice. In vitro experiments showed that GQD protected cells from radiation-induced apoptosis and promoted cell proliferation. Puerarin, baicalein, berberine, and glycyrrhetinic acid were identified as the core active components of GQD against RII. Core active components inhibited the NF-κB pathway to reduce inflammation; modulated the Caspase-9/-3 pathway to abate apoptosis; and activated the Wnt/β-catenin pathway to enhance cell proliferation. CONCLUSIONS: This study provides the first evidence of GQD's efficacy against RII model. The core active components and pathways offer novel insights and potential therapeutic targets for the management of RII.