海南医科大学学报2025,Vol.31Issue(24):1889-1899,11.DOI:10.13210/j.cnki.jhmu.20250218.002
基于网络药理学和动物实验探讨扶阳方治疗缺血性脑中风的作用机制
Mechanism of Fuyang Formula treating ischemic stroke based on network pharmacology and animal experiments
摘要
Abstract
Objective:To explore the core targets and signaling pathways of Fuyang Formula in treating ischemic stroke(IS)based on network pharmacology and molecular docking(MD),and to verify the mechanism of action of Fuyang Formula on IS through middle cerebral artery occlusion(MCAO)rat model.Methods:By using network pharmacology methods to predict the composition of drugs and the core targets of diseases,GO functional enrichment and KEGG signaling pathways were analyzed,and MD was completed using the AutoDock Vina1.1.2 software.By establishing the MCAO rat model,the control group,the model group,the sham surgery group,and the low-dose and high-dose Fuyang Formula groups were treated by gavage.Western blot was used to detect the protein expressions of IL-6,TNF-α,IL-1β,and P-STAT3/STAT3 in each group of rats to verify the effect of Fuyang Formula on IS.Results:There were 143 active ingredients in the traditional Chinese medicine composition of Fuyang Formula,with 172 core targets for treating IS.The main active substances involved included quercetin,kaempferol,luteo-lin,mangiferin,and 7-methoxy-2-methylisoflavone.The core targets included TNF,IL-6,AKT1,IL-1β,TP53,STAT3,EG-FR,JUN,CASP3,and MMP9.The MD results also showed that the screened drugs were effective and could bind well to the core target protein.The biological processes enriched in GO mainly included:positive regulation of gene expression,apoptosis ac-tivity,positive regulation of apoptosis activity,signal transduction,inflammatory activity,and negative regulation of apoptosis ac-tivity,etc.The enrichment of KEGG pathway was related to the IL-17 signaling pathway,lipid and atherosclerosis,TNF signal-ing pathway,fluid shear stress and atherosclerosis,MAPK signaling pathway,and PI3K-Akt signaling pathway,etc.Animal ex-periments showed that the Fuyang Formula traditional Chinese medicine groups could significantly downregulate the protein ex-pression levels of STAT3,IL-6,P-STAT3,IL-1β,and TNF-α in MCAO rat models,and downregulate the P-STAT3/STAT3 values,which are positively correlated with drug solubility.Conclusion:The Fuyang Formula traditional Chinese medi-cine can treat IS through multiple pathways,components,and targets.Experimental verification results show that Fuyang Formu-la can release its therapeutic efficacy for IS by regulating targets related to the TNF signaling pathway.关键词
网络药理学/分子对接/扶阳方/缺血性脑中风/作用机制Key words
Network pharmacology/Molecular docking/Fuyang Formula/Ischemic stroke/Mechanism of action分类
医药卫生引用本文复制引用
ZHAI Yang,MEI Xiaoping,ZOU Min,PANG Xingwang,WANG Han,SHU Jianlong,PANG Yan,WU Haibiao,WEI Yulu,MO Zhizhen,LI Fang..基于网络药理学和动物实验探讨扶阳方治疗缺血性脑中风的作用机制[J].海南医科大学学报,2025,31(24):1889-1899,11.基金项目
This study was supported by the Natural Science Foundation Project of Guangxi Province(2024GXNSFAA010252) (2024GXNSFAA010252)
Guangxi Youth Qihuang Scholar Training Program(GXQH202419) 广西自然科学基金(2024GXNSFAA010252) (GXQH202419)
广西青年岐黄学者培养项目(GXQH202419) (GXQH202419)