Affiliation:
1. School of Pharmacy Anhui University of Traditional Chinese Medicine Hefei China
2. School of Pharmacy Naval Medical University Shanghai China
3. School of Pharmacy Shandong University of Traditional Chinese Medicine Jinan China
4. School of Pharmacy Guangdong Pharmaceutical University Guangzhou China
5. Faculty of Naval Medicine Naval Medicine University Shanghai China
Abstract
AbstractIonizing radiation (IR)‐induced intestinal injury is usually accompanied by high lethality. Intestinal stem cells (ISCs) are critical and responsible for the regeneration of the damaged intestine. Astragalus polysaccharide (APS), one of the main active ingredients of Astragalus membranaceus (AM), has a variety of biological functions. This study was aimed to investigate the potential effects of APS on IR‐induced intestine injury via promoting the regeneration of ISCs. We have established models of IR‐induced intestinal injury and our results showed that APS played great radioprotective effects on the intestine. APS improved the survival rate of irradiated mice, reversed the radiation damage of intestinal tissue, increased the survival rate of intestinal crypts, the number of ISCs and the expression of intestinal tight junction‐related proteins after IR. Moreover, APS promoted the cell viability while inhibited the apoptosis of MODE‐K. Through organoid experiments, we found that APS promoted the regeneration of ISCs. Remarkably, the results of network pharmacology, RNA sequencing and RT‐PCR assays showed that APS significantly upregulated the HIF‐1 signalling pathway, and HIF‐1 inhibitor destroyed the radioprotection of APS. Our findings suggested that APS promotes the regeneration of ISCs through HIF‐1 signalling pathway, and it may be an effective radioprotective agent for IR‐induced intestinal injury.
Funder
National Natural Science Foundation of China
Science and Technology Commission of Shanghai Municipality
Subject
Cell Biology,Molecular Medicine