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

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 (100 mg/kg), and dexamethasone (1 mg/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 100 mg/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 100 mg/kg SIN treated group compared to the placebo (p < 0.05). Conclusions: These findings suggested that the dose of 100 mg/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 (AU)

RESUMEN

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