Baicalein ameliorates ionizing radiation-induced injuries by rebalancing gut microbiota and inhibiting apoptosis.

Abstract Aims Ionizing radiation (IR) induces injuries to the hematopoietic and intestinal systems, which are the leading cause of death. Baicalein, a plant-derived flavonoid, shows anti-oxidative stress, anti-apoptosis, anti-inflammation effects in many diseases. In this study, we evaluated the effects and mechanism of baicalein on IR induced intestinal and hematopoietic injuries. Main methods Mice were divided into three groups: Control, IR and IR + Baicalein. All of mice were intraperitoneally administered with 100 mg/kg baicalein or normal saline for 1 h before IR, and then a day post-IR. The changes in intestinal structure, function and molecular expression were observed by pathological experiments and western blot. 16S rRNA gene sequencing was performed to analyze gut microbiota and further predicted metabolic pathways through Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Hematopoietic function was evaluated by peripheral blood cells count and by flow cytometry analysis of hematopoietic cells composition. Key findings Baicalein improved intestinal structure and the ability of proliferation and regeneration after mice exposed to IR, in which the rebalance of gut microbial composition played an important role. KEGG results showed that p53-related apoptotic pathways played important roles in the composition changes of gut microbiota. Then we observed that baicalein inhibited the activation of p53 and p53 mediated mitochondrial apoptosis and death receptor apoptosis in the intestine. In addition, IR induced injuries to hematopoietic system also could be ameliorated by baicalein. Significance These results provide new insights into the mechanism of baicalein and support the potential of baicalein as a radioprotective medicine.