Molecular mechanism of Taohong Siwu decoction against ischemic stroke based on network pharmacology and animal experiment
Objective To determine the mechanism of Taohong Siwu decoction(THSWD)in ischemic stroke by network pharmacology,molecular docking and in vivo experiment.Methods The common targets of THSWD and disease were analyzed via database collection.Network topology analysis and protein interaction analysis were used to obtain the key components and key targets.The common targets were analyzed by GO and KEGG enrichment.The binding energy of related pathway proteins and key components was obtained by molecular docking.The mouse focal ischemia-reperfusion injury model was established by ligation of middle cerebral artery occlusion reperfusion(MCAO/R).The effect of THSWD on stroke was determined by neurobehavioral tests and TTC staining.Western blot was used to verify the effect of THSWD on the expression of IL-1β,IL-18,PI3K,and AKT in the middle MCAO/R mouse brain.Results The key components of THSWD on ischemic stroke might include quercetin,luteolin,β-sitosterol,kaempferol,stigmasterol,baicalin,myricetin,β-carotene and ivioside.THSWD and the key potential targets of disease included MAPK14,RELA,TNF,TR53,MAPK1,MYC,FOS,HSP9AA1,ESR1,AKT1,HF1A and CTNNB1.The common targets were mainly concentrated in the lipid and atherosclerosis signaling pathways,and PI3K/AKT signaling pathways,which involved in such biological processes as oxidative stress and response to lipopolysaccharide.The molecular docking showed that key components had strong binding affinity to pathway protein.The in vivo experiment assays showed that THSWD decreased the neural function score,reduced the cerebral infarction area,decreased the expression levels of IL-1β and IL-18,and increased the expression levels of PI3K and AKT in the MCAO/R mouse brain.Conclusion THSWT may prevent stroke via the activation of PI3K/AKT signaling pathway to regulate neuritis.
万方数据
维普
