The Protective Effect Of Rosavin From Rhodiola Rosea.L On Radiation-induced Intestinal Injury

Rhodiola rosea L.（RRL）belongs to Crassulaceae plants and the bioactive constitutes from RRL exhibit multiple pharmacological effects on diverse diseases.However,whether they are suitable for the treatment of radiation-induced intestinal injury（RIII）remains unclear.Objective:This study aims to investigate their roles and mechanism in the RIII rat model.Methods:Radioprotection of the 4 bioactive constituents of RRL（salidroside,herbacetin,rosavin and arbutin）was investigated.IEC-6 cells were irradiated by 10 Gy and then treated by the 4 bioactive constituents at different concentrations（6.25μM,12.50μM,25.00μM,50.00μM,100.00μM）for 72h.Cell viability was evaluated by CCk-8 assay and the optimal constituent was used for subsequently experiments.Rats were divided into three groups:nornal group,radiation group and rosavin group.After 14 Gy abdominal radiation,rats were immediately gavaged with PBS or rosavin once.After that,rats were continuously gavaged with PBS or rosavin for 6 days.Survival curves were conducted throughout the14-day experiment.Plasma was collected from 5 rats in each group at day 1,3,5,7 after radiation.The level of D-lactate and D-xylose were measured to evaluate intestinal permeability and absorption function.Sequential segments of proximal jejunum from the ligament of Treitz were collected for histological analysis,including villi length,crypts number,local inflammation and oxidative stress.Results:Our work showed that salidroside,rosavin and arbutin improved the cell viability of the irradiated IEC-6 cells at low concentrations,with the highest improvement in12.50μM rosavin group（cell viability:85.56±4.93%）.Compared with the irradiated rats gavaged with PBS for 7days,the treatment with rosavin significantly improved the survival rate（80.0±0.10%VS 33.3±0.12%,P<0.01）.Compared with radiation group,rosavin treatment showed considerable structure improvement as evidenced by decreased inflammatory cell infiltration,increased crypt number,higher villi.Intestinal epithelium thickness in rosavin group gradually recovered and increased to near normal level on 7^thday.The serum D-lactate concentration was significantly lower than that of the radiation group（P<0.05）and gradually decreased（from 3.18±0.10 ug/ml to 1.51±0.19 ug/ml）.The level of serum D-xylose was significantly higher compared with the radiation group（P<0.05）and gradually increased（from 53.47±3.65 ug/ml to 88.74±6.62 ug/ml）.In addition,rosavin treatment significantly decreased pro-inflammatory factors（P<0.05）and significantly increased antioxidant enzymes（P<0.05）.Results:Our work indicated that rosavin may be the optimal constituent of RRL in RIII by reducing pro-inflammatory factors and enhancing the antioxidant defense system,providing an attractive candidate for radioprotection.