Centella Asiatica Ameliorates Radiation-induced Epithelial Barrier Dysfunction by Secreting Epidermal Growth Factor in Endothelial Cells.

Abstract

BackgroundRadiation-induced intestinal damage is frequently observed following radiotherapy for abdominal and pelvic cancer or occurs due to radiation exposure in a nuclear accident. In an effort to overcome radiation-induced normal tissue damage, a variety of radio-mitigator candidates have been investigated. The loss of the epithelium and its barrier function leads to ‘leaky gut’, so recovery of damaged epithelium is an important strategy in therapeutic trials. Centella asiatica (CA), a traditional herbal medicine in Chinese culture, is widely used for wound healing by protecting against endothelial damage. In this study, we investigated the radio-mitigating effect of CA, focusing on crosstalk between endothelial and epithelial cells.ResultsCA treatment attenuated radiation-induced endothelial dysfunction in human umbilical vein endothelial cells and mitigated radiation-induced enteropathy in a mouse model. In particular, treatment of the conditioned media from CA-treated irradiated endothelial cells recovered loss of epithelial integrity by regulating zonula occludens 1 and desmoglein 2 in radiation exposure. We also determined that epidermal growth factor (EGF) is a critical factor secreted by CA-treated irradiated endothelial cells. Treatment with EGF, which can mimic the effect of CA-induced secretion in irradiated endothelial cells, effectively improved the radiation-induced epithelial barrier dysfunction. In addition, blockade of EGF in CA-induced endothelial secretome impeded epithelial barrier recovery. Finally, we identified the therapeutic effects of CA-induced endothelial secretome in a radiation-induced enteropathy mouse model with epithelial barrier restoration.ConclusionsWe have shown therapeutic effects of CA on radiation-induced enteropathy, with the recovery of endothelial and epithelial dysfunction, focusing on the crosstalk between endothelial cells and epithelial cells. Thus, our finding suggest that CA is an effective radio-mitigator against radiation-induced enteropathy.