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 r...

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Main Authors: Wenjing Xu, Liping Gao, Wenjuan Zou, Xiaohui Tang, Weiqi Nian, Weiqin Zheng, Rongzhong Huang, Pei Wang
Format: Article
Language:English
Published: BMC 2025-02-01
Series:BMC Complementary Medicine and Therapies
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Online Access:https://doi.org/10.1186/s12906-025-04820-2
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author Wenjing Xu
Liping Gao
Wenjuan Zou
Xiaohui Tang
Weiqi Nian
Weiqin Zheng
Rongzhong Huang
Pei Wang
author_facet Wenjing Xu
Liping Gao
Wenjuan Zou
Xiaohui Tang
Weiqi Nian
Weiqin Zheng
Rongzhong Huang
Pei Wang
author_sort Wenjing Xu
collection DOAJ
description 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. SD rats were randomly divided into one of the following groups: control, model, CB1 agonist, CKI and CKI + CB1 antagonist. Except for the control group, the remaining groups were irradiated the abdomen with 6 MV medical high-energy x-ray linear accelerator to establish the model of radiation enteritis. After one week of treatment, the expression of inflammatory factors, SOD and GSH-Px activities, MDA, ROS and NO contents; NF-κB signaling activation and the expression of NOX4, CB1, p38 MAPK, p-p38 MAPK in the ileal tissues of rats were examined to assess the therapeutic effect and possible mechanism of CKI on radiation enteritis, respectively. 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 signaling 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.
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spelling doaj-art-81dbee4be1a04ce593d1abec20d2d89e2025-08-20T03:13:11ZengBMCBMC Complementary Medicine and Therapies2662-76712025-02-0125111310.1186/s12906-025-04820-2Compound kushen injection improves radiation enteritis via cannabinoid receptor 1 in ratsWenjing Xu0Liping Gao1Wenjuan Zou2Xiaohui Tang3Weiqi Nian4Weiqin Zheng5Rongzhong Huang6Pei Wang7Precision Medicine Center, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Oncology, Chongqing Traditional Chinese Medicine HospitalDepartment of Oncology, Chongqing Traditional Chinese Medicine HospitalDepartment of Oncology, Chongqing Traditional Chinese Medicine HospitalDepartment of Oncology, Chongqing Traditional Chinese Medicine HospitalDepartment of Oncology, Chongqing Traditional Chinese Medicine HospitalPrecision Medicine Center, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Oncology, Chongqing Traditional Chinese Medicine HospitalAbstract 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. SD rats were randomly divided into one of the following groups: control, model, CB1 agonist, CKI and CKI + CB1 antagonist. Except for the control group, the remaining groups were irradiated the abdomen with 6 MV medical high-energy x-ray linear accelerator to establish the model of radiation enteritis. After one week of treatment, the expression of inflammatory factors, SOD and GSH-Px activities, MDA, ROS and NO contents; NF-κB signaling activation and the expression of NOX4, CB1, p38 MAPK, p-p38 MAPK in the ileal tissues of rats were examined to assess the therapeutic effect and possible mechanism of CKI on radiation enteritis, respectively. 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 signaling 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.https://doi.org/10.1186/s12906-025-04820-2Network pharmacologyCompound Kushen InjectionRadiation enteritisCannabinoid receptor 1Inflammatory pathwaysOxidative stress
spellingShingle Wenjing Xu
Liping Gao
Wenjuan Zou
Xiaohui Tang
Weiqi Nian
Weiqin Zheng
Rongzhong Huang
Pei Wang
Compound kushen injection improves radiation enteritis via cannabinoid receptor 1 in rats
BMC Complementary Medicine and Therapies
Network pharmacology
Compound Kushen Injection
Radiation enteritis
Cannabinoid receptor 1
Inflammatory pathways
Oxidative stress
title Compound kushen injection improves radiation enteritis via cannabinoid receptor 1 in rats
title_full Compound kushen injection improves radiation enteritis via cannabinoid receptor 1 in rats
title_fullStr Compound kushen injection improves radiation enteritis via cannabinoid receptor 1 in rats
title_full_unstemmed Compound kushen injection improves radiation enteritis via cannabinoid receptor 1 in rats
title_short Compound kushen injection improves radiation enteritis via cannabinoid receptor 1 in rats
title_sort compound kushen injection improves radiation enteritis via cannabinoid receptor 1 in rats
topic Network pharmacology
Compound Kushen Injection
Radiation enteritis
Cannabinoid receptor 1
Inflammatory pathways
Oxidative stress
url https://doi.org/10.1186/s12906-025-04820-2
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