The Radioprotective Effects of (−)-Epigallocatechin-3-gallate (EGCG): Restoring the Gut Microbiota-Immune Axis to Ameliorate Radiation-Induced Intestinal Injury

Objectives: To investigate the protective effect and mechanism of (-)-epigallocatechin-3-gallate (EGCG) against radiation-induced intestinal injury (RIII). Methods: C57BL/6J mice were pretreated with 10 mg/kg EGCG for 10 weeks or 3 days before 10 Gy total body irradiation (TBI) or whole abdominal irradiation (WAI), focusing on survival, body weight, intestinal structure, inflammation, and gut microbiota. For mechanism exploration, peritoneal and RAW264.7 macrophages were pretreated with 0-50 μM EGCG before irradiation, followed by assessments of cell viability, inflammatory proteins, and related signaling. Results: EGCG protects mice from TBI-induced toxicity and weight loss, and alleviates WAI-induced intestinal injury, characterized by preserved villus architecture and reduced crypt cell apoptosis. Mechanistically, EGCG inhibits RIII by suppressing pro-inflammatory cytokine production (TNF-α, IL-6) and maintains the composition of gut microbiota disrupted by irradiation. In vitro studies confirm EGCG directly regulates the release of radiation-induced inflammatory factors in macrophages via inhibiting toll-like receptor (TLR) signaling, independent of microbial effects. The radioprotective effect of EGCG is attributed to its dual actions: preserving macrophage function to dampen inflammatory responses and maintaining gut microbiota homeostasis. Conclusion: These findings highlight EGCG as a potential therapeutic agent for RIII, offering a novel strategy to improve outcomes in irradiated patients.