Mechanisms of Lysionotus pauciflorus Maxim.for the treatment of chronic bronchitis based on bioinformatics
Objective To explore the molecular mechanisms of Lysionotus pauciflorus Maxim.in treating chronic bronchitis(CB)in rats based on bioinformatics.Methods Active components of Lysionotus pauciflorus Maxim.were screened using the Lipinski rule.Potential targets were predicted with UniProt,intersected with disease targets from Gene Cards,and a protein interaction network was created with string to establish a"Component-Target-Pathway"network.Intersection targets were enriched and analyzed using the Gene Ontology Database and the Kyoto Encyclopedia of Genes and Genomes(GO-KEGG),and the docking mode of active components with core targets was simulated with AutoDock.Thirty rats were randomly divided into five groups:control(0.9％NaCl),model(0.9％NaCl),positive drug(1g/kg Guilong cough and asthma relief),low-dose(2 g/kg),and high-dose(8 g/kg)Lysionotus pauciflorus Maxim.groups.After CB modeling,lung tissues were collected for HE staining to judge the success of the modeling;gastric administration was then performed once a day for 28 days.Western blot and RT-PCR were used to detect the expression of proteins and mRNAs such as protein kinase B(AKT1),peroxisome proliferator-activated receptor γ(PPARγ),and nuclear factor-κB(NF-κB p65)in lung tissues;ELISA was used to detect serum levels of tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β),and interferon γ(INF-γ).Results Lysionotus pauciflorus Maxim.had 18 active components with 92 intersecting targets,including core targets like AKT1 and PPARγ.GO-KEGG enrichment mainly involved immune and inflammation-related phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt),mitogen-activated protein kinase(MAPK)signaling pathways.Compared with blank group,PPARγ protein and mRNA expression in lung tissue of model group decreased,while NF-κB p65 and AKT1 protein and mRNA expression increased(P＜0.05).Compared with model group,PPARγ protein and mRNA expression in lung tissue of rats in positive drug group,low-Lysionotus pauciflorus group and high-Lysionotus pauciflorus group were increased to some extent,while NF-κB p65 and AKT1 protein and mRNA expression were decreased to some extent.The difference of lung tissue expression was most significant in high-Lysionotus pauciflorus group(P＜0.05).The active components of Lysionotus pauciflorus Maxim.stably bind to AKT1 and PPARγ.Animal experiments showed that the levels of TNF-α,IL-1 β,and INF-γ in the serum of rats in the model group and low-dose Lysionotus pauciflorus Maxim.group were higher than those in the control group(P＜0.05),and those in the positive drug group and high-dose Lysionotus pauciflorus Maxim.group were lower than those in the model group(P＜0.05).Conclusion Lysionotus pauciflorus Maxim.exerts therapeutic effects on CB by acting on AKT1,PPARγ,and NF-κB p65.
Lysionotus pauciflorus Maxim.chronic bronchitisbioinformatics analysisin vivo experimentslung tissuePI3K-AKT signaling pathway
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