Berberine alleviates radiation-induced intestinal injury by inhibiting cellular senescence

OBJECTIVES: The aim was to study the inhibitory effect of berberine (BBR) on intestinal senescence induced by radiation and explore its mechanism. METHODS: Male C57BL/6J mice and SD rats were randomly divided into three groups: Control, irradiation (IR), and IR + BBR. Except for the normal control group, which received sham irradiation, the other two groups were subjected to abdominal X-ray irradiation (12 Gy for mice and 15 Gy for rats). Mesenteric blood flow was detected using laser speckle blood flow contrast imaging. Senescence markers were evaluated using RT-qPCR, Western blot analysis, and SA-β-Gal staining. 16S rRNA sequencing technology was used to study the changes in the intestinal microbiota. MRI was used to evaluate the efficacy of BBR on intestinal injury. RESULTS: Our results showed that BBR can alleviate radiation-induced DNA damage and senescence in mouse intestines, mitigate both acute and chronic radiation-induced intestinal damage, and is accompanied by an improvement in intestinal flora imbalance. In addition, BBR enhances the survival and proliferative capacity of irradiated intestinal epithelial cells, inhibits radiation-induced cellular senescence and SASP in vitro, and prevents cells from entering senescence. The underlying mechanism may involve the activation of the Nrf2-related pathway. CONCLUSION: Our findings suggest that BBR can effectively alleviate the intestinal cellular senescence caused by radiation, concomitant with the remodeling of gut microbiota, which provides potential implications for using BBR as a drug against radiation-induced intestinal injury.