BACKGROUND: Radiation-induced Intestinal Injury (RIII) affects quality of life in radiotherapy patients
Liangxue Guyuan Yishen Decoction (LGYD) offers protection but requires further study on its mechanism. PURPOSE: The aim of this study was to investigate the heterogeneity of cellular responses in the intestine at a single-cell level following radiation and LGYD treatment. STUDY DESIGN: This study's design includes in vivo and in vitro assessments to evaluate LGYD's effects on intestinal cells post-radiation, targeting survival, recovery, and molecular pathways. METHODS: Mice were categorized into four groups: LGYD group, NC group, IR group, and Am group. Each group received daily drug administrations. All groups, except for the NC group, were subjected to a single whole-body irradiation at a dose rate of 70 R/min with a source-to-skin distance of 250 cm. Subsequent experiments were conducted following the irradiation, which led to severe survival impairments in the mice. RESULTS: Our findings demonstrate that LGYD intervention substantially improves survival rates following lethal doses (8.5 Gy, 70R/min) of whole-body irradiation. Moreover, LGYD expedites the recovery period for intestinal injury on the fifth day after radiation by promoting repair mechanisms within intestinal tissue, with particular focus on mitigating intestinal stem cells (ISCs) damage and immune disorders. Through both in vivo and in vitro experiments, we have discovered that LGYD effectively treats RIII by activating Hes1 transcription factor activity through its key active ingredients in drug-containing serum. This activation further upregulates the downstream Stat3 and Akt gene, thereby facilitating repair processes within intestinal stem cells. CONCLUSION: In this study, we discovered that LGYD can enhance the downstream expression and phosphorylation pathways of Stat3 and Akt by upregulating the expression of Hes1 gene following high-dose radiation exposure.