Evaluation of Safety of Compound Kushen Injection and Efficacy in Treatment of Inflammatory Bowel Disease Based on Zebrafish Model
10.13422/j.cnki.syfjx.20241314
- VernacularTitle:基于斑马鱼模型的复方苦参注射液安全性及治疗炎症性肠病的有效性评价
- Author:
Xiaolu CHEN
1
;
Jiaqi LI
1
;
Linzhen CHEN
1
;
Qi CHEN
1
;
Zhiqiang MA
1
;
Chongjun ZHAO
1
Author Information
1. Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medical/Traditional Chinese Medicine（TCM） Processing Technology Inheritance Base of National Administration of TCM， School of Chinese Materia Medica， Beijing University of Chinese Medicine， Beijing 102488， China
- Publication Type:Journal Article
- Keywords:
zebrafish;
compound Kushen injection;
inflammatory bowel disease;
safety;
efficacy;
mechanism
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(4):71-78
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo evaluate the safety/efficacy of compound Kushen injection （CKI） by zebrafish model and explore the possible mechanism. MethodsZebrafish were exposed to different concentrations of CKI solution， and the mortality rate after 24 h was calculated. After exposure to sublethal concentration （10） and safe dose concentration （0） for 24 h， the safety of CKI was evaluated based on acridine orange staining for the liver， liver area changes， and liver histological sections. The inflammatory bowel disease （IBD） model of zebrafish was established with 2，4，6-trinitrobenzenesulfonic acid sol （TNBS）. The efficacy of CKI in the treatment of IBD was evaluated by the changes in the area of neutral red staining， the number of neutrophils， the area of alcian blue staining， and the contents of tight junction protein （Occludin）， zonula occludens-1 （ZO-1）， tumor necrosis factor（TNF）-α， and prostaglandin E2（PGE2） in the intestine of zebrafish. The mechanism of CKI in the treatment of IBD was predicted by network pharmacology and verified by real-time polymerase chain reaction（Real-time PCR）. ResultsIn the safety evaluation， compared with the blank group， the sublethal concentration of CKI could cause liver cell apoptosis， liver area reduction， loose and disordered arrangement of liver cell structure， obvious vacuolation， and other pathological characteristics of zebrafish， while these indicators showed no significant changes under safe dose conditions. In the effectiveness evaluation， compared with the model group， the safe dose of CKI could increase the neutral red staining area of the intestine in a dose-dependent manner and improve the intestinal phagocytosis function. It could reduce the accumulation of intestinal neutrophils， increase the alcian blue staining area， enhance intestinal goblet cell secretion， improve the contents of Occludin and ZO-1， and decrease the contents of TNF-α and PGE2. Network pharmacology analysis identified 288 potential targets for CKI treatment of IBD. The top five targets obtained by protein-protein interaction （PPI） network analysis were epidermal growth factor receptor A（EGFRA）， protein kinase B1（Akt1）， heat shock protein 90（HSP90AA1）， homologous oncogene of avian sarcoma virus（SRC）， and protooncogene （JUN）. Kyoto encyclopedia of genes and genomes（KEGG） results showed that CKI may be related to the Wnt signaling pathway and cholinergic synaptic pathway in the treatment of IBD， and Real-time PCR results verified the above pathways. ConclusionExcessive use of CKI can induce obvious liver injury in zebrafish， while the rational use of CKI does not cause obvious toxic reactions and can achieve a therapeutic effect on IBD by regulating the Wnt pathway.
