Ginsenoside Rb1 mitigates radiation-induced intestinal injury through Treg expansion and IL-10-mediated epithelial regeneration.

BACKGROUND: Radiation-induced enteropathy represents a key limitation to recovery after accidental radiation exposure or radiotherapy, with few effective pharmacological treatments. We investigated the therapeutic potential of ginsenoside Rb1, a major saponin from Panax ginseng, in attenuating the radiation-induced intestinal injury. METHODS: C57BL/6 mice were exposed to abdominal irradiation at a dose of 13.5 Gy and treated with Rb1. The epithelial integrity, bacterial translocation, and immune modulation were assessed. In vitro, rat intestinal epithelial cell line, IEC-6 were examined for proliferation and Wnt/β-catenin activation in response to Rb1 and IL-10. The role of IL-10 was validated using neutralization experiments. RESULTS: Rb1 significantly alleviated radiation-induced crypt damage, villus shortening, bacterial translocation, and inflammation. It enhanced regulatory T (Treg) cell population and IL-10 secretion, which in turn activated Wnt/β-catenin signaling and promoted epithelial regeneration. In vitro, IL-10, but not Rb1 directly, promoted the proliferation of irradiated IEC-6 cells, whereas IL-10 neutralization abolished the mitigative effect of Rb1 in vivo. CONCLUSION: Rb1 mitigated radiation-induced enteropathy by upregulating Treg abundance and IL-10 signaling, which in turn activated epithelial regeneration with Wnt/β-catenin pathway activation, supporting its potential as a therapeutic agent for radiation-induced intestinal injury.