Cornuside ameliorates airway inflammation via toll-like receptor 4 and Notch1 in asthmatic mice induced by lipopolysaccharide and ovalbumin

To determine the potential role of cornuside in the regulation of allergic airway inflammation in lipopolysaccharide (LPS) and ovalbumin (OVA)-induced asthma. BALB/c mouse model of LPS and OVA-induced asthma was used to evaluate the effect of cornuside on Toll-like receptor 4 (TLR4) and Nocth1 signaling pathway. Hematoxylin and eosin staining was performed for histological studies of murine lung tissues. Enzyme-linked immunosorbent assay was employed to measure protein levels in serum, while Western blotting was carried out for the determination of protein expression in tissues. Airway hyperresponsiveness was measured 2 days after the last OVA challenge. After induction by LPS and OVA, the mice had increased numbers of inflammatory cells, increased levels of IL-4, IL-5 and IL-13 in bronchoalveolar lavage fluids (BAL) and lung tissues, increased total and OVA-specific IgE levels in serum and increased expression of TLR4 and Nocth1 and phosphorylation of STAT3 in lung tissues. Administration of cornuside markedly reduced airway inflammatory cell recruitment and peribronchiolar inflammation, decreased the production of various cytokines in BAL fluids and lung tissues, and lowered the levels of total and OVA-specific IgE in serum. In addition, the increased expression of TLR4 and Nocth1 and phosphorylation of STAT3 after LPS and OVA inhalation was inhibited by the administration of cornuside. The present study demonstrates that the signaling pathway between TLR4 and Notch1 may be able to coordinate with STAT3 and cornuside regulates TLR4 and Nocth1 signaling pathway to attenuate allergic airway inflammation in LPS and OVA-induced asthma. These findings provide a crucial molecular mechanism for the potential use of cornuside to prevent and/or treat asthma and other airway inflammatory disorders.