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| PI3K/AKT signaling pathway is involved in the molecular mechanism of Changpu Shenmai Decoction in improving neurological deficits after acute cerebral infarction |
| Hits 60 Download times 30 Received:April 20, 2024 |
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| DOI
10.11656/j.issn.1673-9043.2024.09.06 |
| Key Words
acute cerebral infarction;Changpu Shenmai Decoction;Buqi Fuzheng therapy;PI3K/AKT signaling pathway;network pharmacology;MCAO model |
| Author Name | Affiliation | E-mail | | LIU Jinghe | Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China | | | ZHENG Yilan | Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China | | | YANG Qinru | Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China | | | LIU Xian | Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China | | | CAO Kegang | Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
Institute of Traditional Chinese medicine Encephalopathy, Beijing University of Chinese Medicine, Beijing 100027, China | | | XU Yingzhi | Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
Institute of Traditional Chinese medicine Encephalopathy, Beijing University of Chinese Medicine, Beijing 100027, China | | | TANG Lu | Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China | tanglu0310@126.com |
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| Abstract
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| [Objective] To explore the potential molecular mechanism of Changpu Shenmai Decoction in the treatment of acute cerebral infarction(ACI) based on network pharmacology and molecular docking technology,and to conduct a preliminary study through animal experiments. [Methods] The active ingredients and component targets of Acorus calorus ginseng wheat recipe were retrieved from Traditional Chinese Medicine Systems Pharmacology Database(TCMSP) and Batmanic-TCM databases,and the potential targets of acute cerebral infarction were obtained from GeneCards,Online Mendelian Inheritance in Man Database(OMIM),PharmGkb and DrugBank databases. Cytoscape 3.9.1 software was used to construct the network diagram of "active ingredients-potential targets" in the treatment of ACI. The STRING database was used to construct the PPI network and screen the core target genes. R language software was used to perform Gene Ontology(GO) gene function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. Finally,Autodock software was used for molecular docking,and Pymol software was used for mapping to observe the hydrogen bond formation between the core target and the core active component. The middle cerebral artery occlusion(MCAO) model was constructed,and the drug efficacy,pharmacology and molecular docking results were preliminarily verified by neurological function score,grip strength test,rotarod test,triphenyltetrazolium chloride(TTC) staining and Western blot. [Results] A total of 270 potential targets for the treatment of acute cerebral infarction,corresponding to 55 active components,were obtained by mapping the targets of active components of Acorus calarinosus and ACI. Five core targets including estrogen receptor 1(ESR1),mitogen-activated protein kinase 14(MAPK14),v-akt murine thymoma viral oncogene homolog 1(AKT1),Caspase-3 and Caspase-9 were screened after Protein-Protein Interaction Network Analysis(PPI) network analysis and calculation. GO functional enrichment analysis obtained 3129 items. After enrichment,it was found that they were mainly involved in biological processes such as the reaction to oxygen and the reaction to foreign bodies. A total of 188 signaling pathways were screened by Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis,suggesting that the mechanism may be related to Advanced glycosylation end product-specific receptor(AGE-RAGE),phosphatidylinositide 3-kinases-protein kinase B(PI3K-AKT) and other signaling pathways. Molecular docking results showed that the core components docked well with the core targets. Animal experiments showed that Changpu Shenmai Decoction could improve the neurological function(P<0.005),grip strength(P<0.001) and movement time on the rod(P<0.001),reduce the area of cerebral infarction(P<0.001),up-regulate the ratio of p-AKT/AKT(P<0.001) and down-regulate the expression of Caspase-9(P<0.001) in rats,and its brain protective effect was significantly weakened by the use of PI3K inhibitor LY294002. [Conclusion] The pharmacological effect of Changpu Shenmai Decoction on acute cerebral infarction is achieved through the regulation of multi-components,multi-targets and multi-pathways,and its mechanism may be related to the activation of PI3K/AKT signaling pathway. |
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