Anti-inflammatory effects of reticuline on the JAK2/STAT3/SOCS3 and p38 MAPK/NF-κB signaling pathway in a mouse model of obesity-associated asthma

Clin Respir J. 2024 Jan;18(1):e13729. doi: 10.1111/crj.13729.

Abstract

Background: Asthma associated with obesity is a chronic disease characterized by earlier airway remodeling, severe wheezing, and increased insensitivity to hormone therapy. Reticuline, a bioactive compound of Magnoliae Flos, exerts anti-inflammatory activity and can inhibit neutrophil recruitment. Thus, this study investigated the role of reticuline in obesity-related asthma.

Methods: The BALB/c mice fed a low-fat diet (LFD) and high-fat diet (HFD) were intranasally challenged with house dust mites (HDMs) or ovalbumin (OVA). Reticuline (0.25 mg/kg) was administrated into mice by intragastrical gavage. Airway hyper-responsiveness was examined after the final challenge. Body weight was measured, and bronchoalveolar lavage fluid (BALF) and lung tissues were collected. The number of inflammatory cells in BALF was estimated. Histological changes were assessed by performing hematoxylin-eosin staining, and production of proinflammatory cytokines and IgE was examined by ELISA kits. Related pathways were studied with western blotting.

Results: Reticuline suppressed airway resistance and inflammatory infiltration in lung tissue and reduced inflammatory cell recruitment in BALF in obesity mice with asthma. Additionally, the levels of IL-17A, IL-1β, IL-5, macrophage inflammatory protein 2, and regulated on activation, normal T cell expressed and secreted in the lung were reduced by reticuline. Mechanistically, reticuline inactivated the JAK2/STAT3/SOCS3 and p38 MAPK/NF-κB signaling pathways in obesity-related asthma.

Conclusion: Reticuline alleviates airway inflammation in obesity-related asthma by inactivating the JAK2/STAT3/SOCS3 and p38 MAPK/NF-κB signaling pathways.

Keywords: JAK/STAT; SOCS3; asthma; inflammation; neutrophil; obesity.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Asthma* / drug therapy
  • Asthma* / metabolism
  • Benzylisoquinolines* / pharmacology
  • Benzylisoquinolines* / therapeutic use
  • Bronchoalveolar Lavage Fluid
  • Cytokines / metabolism
  • Disease Models, Animal
  • Inflammation / metabolism
  • Janus Kinase 2* / drug effects
  • Janus Kinase 2* / metabolism
  • Lung / pathology
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B* / drug effects
  • NF-kappa B* / metabolism
  • Obesity / complications
  • Obesity / drug therapy
  • STAT3 Transcription Factor* / drug effects
  • STAT3 Transcription Factor* / metabolism
  • Signal Transduction
  • Suppressor of Cytokine Signaling 3 Protein / drug effects
  • Suppressor of Cytokine Signaling 3 Protein / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism
  • p38 Mitogen-Activated Protein Kinases / pharmacology
  • p38 Mitogen-Activated Protein Kinases / therapeutic use

Substances

  • Anti-Inflammatory Agents
  • Benzylisoquinolines
  • Cytokines
  • JAK2 protein, human
  • Janus Kinase 2
  • NF-kappa B
  • p38 Mitogen-Activated Protein Kinases
  • reticuline
  • SOCS3 protein, human
  • STAT3 protein, human
  • STAT3 Transcription Factor
  • Suppressor of Cytokine Signaling 3 Protein