Compound Kushen Injection improves radiation enteritis via cannabinoid receptor 1 in rats

Abstract

Background: Clinical studies have shown that Compound Kushen Injection (CKI) can alleviate the inflammatory symptoms of radiation enteritis. However, the mechanism of action remains unclear. The aim of this study was to explore the possible targets and mechanisms of CKI in the treatment of radiation enteritis. Methods: Network pharmacology was used to predict the potential targets of CKI for the treatment of radiation enteritis, and GO and KEGG enrichment analyses were subsequently performed. The therapeutic effects and signalling pathways were then verified in rats. The expression of inflammatory factors in ileal tissue was measured by qRT-PCR. The activities of SOD and GSH-Px in ileal tissue were measured by ELISA. The levels of MDA, ROS and NO were determined using biochemical kits. The expression of signalling pathway-related proteins was detected by Western blotting and immunofluorescence. Results: According to network pharmacology, CB1 might be a target of CKI. GO and KEGG enrichment analyses revealed that CKI was significantly enriched in analgesic, endocannabinoid and inflammatory pathways. In the rat model, Compared with that in the radiotherapy group,the extent of ileal injury was significantly improved in the CKI group compared to the control group. In addition, the infiltration of CD68 and CD16b was significantly reduced, and the expression of MCP1, TNF-α, IL-1β and IL-10 was significantly decreased. In addition, the activities of SOD and GSH-Px were increased, and the activities of MDA, ROS and NO were decreased. The CKI group also showed inhibition of NF-κB signalling and a significant decrease in the expression of NOX4, CB1 and p-p38 MAPK/p38 MAPK. The use of a CB1 agonist could also alleviate radiation enteritis, whereas the addition of a CB1 antagonist could interfere with the ameliorative effect of CKI on radiation enteritis. Conclusions: CKI might exert an anti-radiation enteritis effect by targeting the cannabinoid receptor 1.