广东药科大学学报2023，Vol.39Issue(6)：15-23,9.DOI:10.16809/j.cnki.2096-3653.2023070602
基于网络药理学和动物实验探究穿心莲内酯对5-Fu所致大鼠化疗性肠黏膜炎的预防作用
Mechanism of improvement effect of andrographolide on 5-Fu-induced chemotherapeutic intestinal mucositis in rats based on network pharmacology and animal experiment
摘要
Abstract
Objective To evaluate the prevention and treatment efficacy of andrographolide in 5-Fu induced chemotherapeutic intestinal mucositis(CIM)in rats based on network pharmacology and animal experiment,so that provide reference for its clinical application.Methods The Swiss Target Prediction,SuperPred,Genecards and OMIM databases were searched to obtain the action targets and corresponding disease targets of andrographolide,and the intersection of action targets and obtained disease targets was taken as the potential targets.The String platform was used to construct a protein-protein interaction network(PPI)for potential targets.The R language software package was used to analyze the function of Gene Ontology(GO)and the enrichment of Kyoto Encyclopedia of Genes and Genomes(KEGG).Cytoscape software was used to analyze its network topology,which was applied to screen the core targets.The key core targets and andrographolide were verified by molecular docking.Thirty-five SD rats were randomly divided into five groups:blank group,model group,positive drug group(bifidobacterium aureus,700 mg/kg),low dose group of andrographolide(30 mg/kg)and high dose group of andrographolide(100 mg/kg).Each group was given intragastric administration of corresponding drugs for 10 days,while blank and model group were given corresponding volume of normal saline.Starting from day 6,each group except the blank group was injected intraperitoneally with 30 mg/kg 5-fluorouracil for 5 days,and the blank group was injected with corresponding volume of normal saline.Body weight and diarrhea of rats were observed and recorded daily.Liver and spleen were collected after the animals were killed,and organ index was calculated.The pathological changes of intestinal tissue in rats were observed by HE staining.ELISA was used to measure the level of serum inflammatory factors IL-6 and TNF-α.Results There are 190 potential targets for the treatment of CIM with andrographolide.In the PPI network,20 core targets such as STAT3,TNF,and IL6 were screened.GO enrichment analysis yielded 2 315 biological process related entries,184 molecular function related entries,and 101 cell component related entries,mainly involving oxidative stress response,positive regulation of MAPK cascade,and cell response to chemical stress.KEGG pathway enrichment analysis revealed 177 related signaling pathways,mainly involving HIF-1,TNF,Toll like receptors,and T cell receptor signaling pathways.The molecular docking results indicated that andrographolide has good binding activity with key core targets STAT3,TNF,and IL-6.The animal experiment results showed that compared with the blank group,the model group rats had a decrease in body mass,severe diarrhea,decreased organ index,severe intestinal tissue damage,and significantly increased serum TNF-α and IL-6 levels.Compared with the model group,the high-dose group of andrographolide reduced the rate of body mass decline,decreased diarrhea score,increased organ index,and reduced damage to the distal ileum tissue.The serum TNF-α and IL-6 content was significantly reduced(P<0.05).Conclusion Andrographolide exerts its effect on the treatment of CIM through multi-target and multi-pathway,and its mechanism may be related to the inhibition of TNF-α and IL-6 proinflammatory cytokines.关键词
穿心莲内酯/化疗所致肠黏膜炎/药效/网络药理学Key words
andrographolide/chemotherapeutic-intestinal-mucositis/pharmacodynamics/network pharmacology分类
医药卫生引用本文复制引用
邱雨馨,邝杰辉,朱俊锦,林曼静,邵艳华..基于网络药理学和动物实验探究穿心莲内酯对5-Fu所致大鼠化疗性肠黏膜炎的预防作用[J].广东药科大学学报,2023,39(6):15-23,9.基金项目
广东省医学科研基金资助项目(A2021181) （A2021181）
广东省中医药局科研项目(20212124) （20212124）
