Sinomenine ameliorates the airway remodelling, apoptosis of airway epithelial cells, and Th2 immune response in a murine model of chronic asthma

Allergol Immunopathol (Madr). 2018 Jan-Feb;46(1):67-75. doi: 10.1016/j.aller.2017.05.004. Epub 2017 Aug 1.

Abstract

Background: Sinomenine (SIN), an alkaloid isolated from the root of Sinomenium acutum which has a variety of pharmacological effects, including anti-inflammation, immunosuppression and anti-angiogenesis. The present study aimed to evaluate the effects of SIN on airway remodelling, epithelial apoptosis, and T Helper (Th)-2 derived cytokine levels in a murine model of chronic asthma.

Methods: Twenty-two BALB/c mice were divided into four groups; I (control), II (placebo), III, IV. Mice in groups III and IV received the SIN (100mg/kg), and dexamethasone (1mg/kg) respectively. Epithelium thickness, sub-epithelial smooth muscle thickness, number of mast and goblet cells of samples isolated from the lung were measured. Immunohistochemical scorings of the lung tissue for matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEG-F), transforming growth factor-beta (TGF-β), terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling (TUNEL) and cysteine-dependent aspartate-specific proteases (caspase)-3 were determined. IL-4, IL-5, IL-13, Nitric oxide in bronchoalveolar lavage fluid (BALF) and ovalbumin-specific immunoglobulin (Ig) E in serum were quantified by standard ELISA protocols.

Results: The dose of 100mg/kg SIN treatment provided beneficial effects on all of the histopathological findings of airway remodelling compared to placebo (p<0.05). All cytokine levels in BALF and serum and immunohistochemical scores were significantly lower in 100mg/kg SIN treated group compared to the placebo (p<0.05).

Conclusions: These findings suggested that the dose of 100mg/kg SIN improved all histopathological changes of airway remodelling and its beneficial effects might be related to modulating Th-2 derived cytokines and the inhibition of apoptosis of airway epithelial cells.

Keywords: Airway remodelling; Angiogenesis; Apoptosis; Asthma; Murine model; Sinomenine; Th2.

MeSH terms

  • Airway Remodeling / drug effects
  • Animals
  • Apoptosis
  • Asthma / drug therapy*
  • Cells, Cultured
  • Chronic Disease
  • Cytokines / metabolism
  • Disease Models, Animal
  • Humans
  • Immunity
  • Immunologic Factors / therapeutic use*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Morphinans / therapeutic use*
  • Respiratory Mucosa / drug effects*
  • Respiratory Mucosa / pathology
  • Sinomenium / immunology
  • Th2 Cells / drug effects*
  • Th2 Cells / immunology

Substances

  • Cytokines
  • Immunologic Factors
  • Morphinans
  • sinomenine