An anti‐asthmatic activity of natural Toll‐like receptor‐4 antagonist in OVA OVA ‐ LPS LPS ‐induced asthmatic rats

摘要

Summary Toll‐like receptor‐4 ( TLR 4) is a key component of the innate immune system and activation of TLR 4 signaling has a significant role in the pathogenesis of asthma. Therefore, our objective was to identify the natural TLR 4 antagonist and evaluate its activity in experimentally induced asthma. Soya lecithin origin phosphatidylcholine (soya PC ) was identified as a natural TLR 4 antagonist by computational study. Based on the computational study, TLR 4 antagonist activity of soya PC was confirmed in in vitro lipopolysaccharide ( LPS )‐induced neutrophil adhesion assay. In the in vivo study, rats were sensitized with ovalbumin ( OVA ) (100?μg/kg, i.p.) on the 7th, 14th and 21st days and challenged intranasally with OVA (100?μg/100?μL) and LPS (10?ng/100?μL), 4?days/wk for 3?weeks. At the end of the experiment, we performed lung function parameters (respiratory rate, tidal volume, airflow rate), inflammatory cytokines (interleukin [ IL ]‐4, IL ‐5, IL ‐13), total and differential leukocytes in blood as well as bronchoalveolar lavage fluid ( BAL f) and histological examinations. The computational study indicated that TLR 4 antagonist activity of soya PC is due to linoleic acid (18:2) fatty acid chain. Soya PC significantly suppressed the LPS ‐induced neutrophil adhesion in a concentration‐dependent manner to 1?μg/ mL . The treatment of soya PC (5 and 10?mg/kg, 18?days, i.p.) significantly improved the lung function parameters, total and differential leukocyte counts in blood and BAL f in asthmatic rats. This efficacy of soya PC was in extent similar to dexamethasone (2.5?mg/kg, 18?days, i.p.). However, soya PC was superior to dexamethasone in terms of benefits. The protective action of soya PC may be due to TLR 4 antagonist activity and linoleic acid composition.