Oxysophocarpine inhibits airway inflammation and mucus hypersecretion through JNK/AP-1 pathway in vivo and in vitro

Fitoterapia. 2022 Oct:162:105278. doi: 10.1016/j.fitote.2022.105278. Epub 2022 Aug 12.

Abstract

Asthma is a high-incidence disease in the world. Oxysophocarpine (OSC), a quinolizidine alkaloid displays various pharmacological functions including anti-inflammation, neuroprotective, anti-virus and antioxidant. Here, we established mice and cell asthmatic model to explore the effects of OSC for asthma treatment. Mice were sensitized and challenged with ovalbumin (OVA) and treated with OSC before challenge. Enzyme-linked immuno sorbent assay (ELISA), hematoxylin and eosin (H&E), periodic acid-schiff (PAS), tolonium chloride staining and immunohistochemical assay were performed. OSC treatment inhibited inflammatory cell infiltration and mucus secretion in the airway, reduced IgE level in mouse serum and decreased IL-4, IL-5 production in bronchoalveolar lavage fluid (BALF). OSC also reduced the spleen index to regulate immune function. Meanwhile, NCI-H292 cells were induced by lipopolysaccharide (LPS) to simulate airway epithelial injury. OSC pretreatment decreased the IL-6 and IL-8 cytokine levels, mucin 5 AC expression, and mucin 5 AC mRNA level in the cell model. Further, OSC suppressed the phosphorylation of c-Jun N-terminal kinase (JNK), and activator protein 1 (AP-1, Fos and Jun). These findings revealed that OSC alleviated bronchial asthma associated with JNK/AP-1 signaling pathway.

Keywords: Airway inflammation; Asthma; JNK/AP-1 signaling pathway; Mucin; Oxysophocarpine.

MeSH terms

  • Alkaloids* / metabolism
  • Alkaloids* / pharmacology
  • Animals
  • Antioxidants / pharmacology
  • Asthma* / drug therapy
  • Cytokines / metabolism
  • Disease Models, Animal
  • Eosine Yellowish-(YS) / metabolism
  • Eosine Yellowish-(YS) / pharmacology
  • Eosine Yellowish-(YS) / therapeutic use
  • Hematoxylin / metabolism
  • Hematoxylin / pharmacology
  • Hematoxylin / therapeutic use
  • Immunoglobulin E
  • Interleukin-4 / metabolism
  • Interleukin-4 / pharmacology
  • Interleukin-4 / therapeutic use
  • Interleukin-5 / metabolism
  • Interleukin-5 / pharmacology
  • Interleukin-5 / therapeutic use
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Lipopolysaccharides / pharmacology
  • Lung
  • Mice
  • Mice, Inbred BALB C
  • Molecular Structure
  • Mucins / metabolism
  • Mucins / pharmacology
  • Mucins / therapeutic use
  • Mucus / metabolism
  • Ovalbumin / metabolism
  • Periodic Acid / metabolism
  • Periodic Acid / pharmacology
  • Periodic Acid / therapeutic use
  • Quinolizidines* / pharmacology
  • RNA, Messenger / metabolism
  • Tolonium Chloride / metabolism
  • Tolonium Chloride / pharmacology
  • Tolonium Chloride / therapeutic use
  • Transcription Factor AP-1 / metabolism
  • Transcription Factor AP-1 / pharmacology
  • Transcription Factor AP-1 / therapeutic use

Substances

  • Alkaloids
  • Antioxidants
  • Cytokines
  • Interleukin-5
  • Interleukin-6
  • Interleukin-8
  • Lipopolysaccharides
  • Mucins
  • Quinolizidines
  • RNA, Messenger
  • Transcription Factor AP-1
  • Periodic Acid
  • Tolonium Chloride
  • Interleukin-4
  • Immunoglobulin E
  • oxysophocarpine
  • Ovalbumin
  • JNK Mitogen-Activated Protein Kinases
  • Eosine Yellowish-(YS)
  • Hematoxylin