摘要
Objective:To investigate the effect and mechanism of Hyssopus cuspidatus Boriss.extract(HCE)in ovalbumin(OVA)-induced allergic asthma.Methods:Components identification of HCE was conducted using ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry.Mice were sensitized with OVA to establish asthmatic model,and dexamethasone was used as positive control.Respiratory reactivity,white cells counting in bronchoalveolar lavage fluid and peripheral blood,cytokine level measurement in serum and lung tissue,and histologic examination were performed to evaluate the therapeutic effect of HCE on asthma.Network pharmacology approach was used for mechanism prediction.Western blotting and untargeted lipidomics method were applied for mechanism validation.Results:Fifty-two compounds were identified in HCE,predominantly terpenoids and flavonoids.HCE markedly reduced airway resistance,the eosinophil infiltration in lung tissues,and the levels of immunoglobulin E,interleukin-4,interleukin-5,and interleukin-13.Network pharmacology analysis suggested phosphatidylinositol 3-kinases(PI3K),c-Jun N-terminal kinase(JNK),and p38 Mitogen-activated protein kinase(p38 MAPK)may be key proteins of HCE in the treatment of allergic asthma.Western blot results indicated that the levels of phosphorylated PI3K,JNK,and P38 were downregulated in HCE-treated group.Moreover,HCE significantly upregulated the levels of ceramide and sphingomyelin and downregulated the level of phosphatidylcholine.Conclusion:HCE inhibited allergic asthma via PI3K/JNK/P38 signaling pathway and lipid homeostasis regulation.
基金
financially supported by National Natural Science Foundation of China(No.82474186,31000150)
the Fundamental Research Funds for the Central Universities,HUST(No.2016YXMS145)。
