The volatile oil of Hyssopus cuspidatus Boriss. (HVO) ameliorates OVA-induced allergic asthma via inhibiting PI3K/Akt/JNK/P38 signaling pathway and maintaining airway barrier integrity

J Ethnopharmacol. 2024 Nov 15:334:118568. doi: 10.1016/j.jep.2024.118568. Epub 2024 Jul 11.

Abstract

Ethnopharmacological relevance: Hyssopus cuspidatus Boriss., a classic Uyghur medicine, is used to treat inflammatory lung diseases such as asthma. But the therapeutic effect and mechanism of the volatile oil of Hyssopus cuspidatus Boriss.(HVO) in asthma therapy remain unclear.

Aim of the study: We aim to characterize the constituents of HVO, investigate the therapeutic effect in OVA-induced allergic asthmatic mice and further explore the molecular mechanism.

Materials and methods: In this study, we applied two-dimensional gas chromatography quadrupole time-of-flight mass spectrometry (GC × GC-QTOF MS) to identify the ingredients of HVO. We established OVA-induced asthmatic model to investigate the therapeutic effect of HVO. To further explore the potential molecular pathways, we used network pharmacology approach to perform GO and KEGG pathways enrichment, and then built an ingredient-target-pathway network to identify key molecular pathways. Finally, LPS-induced RAW 264.7 macrophages and OVA-induced asthmatic model were used to validate the potential signaling pathways.

Results: GC × GC-QTOF MS analysis revealed the presence of 123 compounds of HVO. The sesquiterpenes and monoterpenes are the main constituents. The in vivo study indicated that HVO suppressed OVA-induced eosinophilic infiltration in lung tissues, inhibited the elevation of IgE, IL-4, IL-5, and IL-13 levels, downregulated the expressions of phosphorylated PI3K, Akt, JNK and P38, and maintained epithelial barrier integrity via reducing the degradation of occludin, Zo-1, Zo-2, and E-cadherin. The in vitro study also revealed an inhibition of NO release and downregulation of phosphorylated PI3K, Akt, JNK and P38 levels.

Conclusion: HVO alleviates airway inflammation in OVA-induced asthmatic mice by inhibiting PI3K/Akt/JNK/P38 signaling pathway and maintaining airway barrier integrity via reducing the degradation of occludin, Zo-1, Zo-2, and E-cadherin.

Keywords: Airway barrier integrity; Allergic asthma; Hyssopus cuspidatus Boriss.; PI3K/Akt/JNK/P38 signaling pathway; Volatile oil.

MeSH terms

  • Animals
  • Anti-Asthmatic Agents / pharmacology
  • Asthma* / chemically induced
  • Asthma* / drug therapy
  • Disease Models, Animal
  • Female
  • MAP Kinase Signaling System / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Oils, Volatile* / chemistry
  • Oils, Volatile* / pharmacology
  • Ovalbumin*
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Pyroglyphidae / immunology
  • RAW 264.7 Cells
  • Signal Transduction / drug effects
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Anti-Asthmatic Agents
  • Oils, Volatile
  • Ovalbumin
  • p38 Mitogen-Activated Protein Kinases
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt