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An anti‐asthmatic activity of natural Toll‐like receptor‐4 antagonist in OVA ‐ LPS ‐induced asthmatic rats
Author(s) -
Thakur Vandana R.,
Beladiya Jayesh V.,
Chaudagar Kiranj K.,
Mehta Anita A.
Publication year - 2018
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.13002
Subject(s) - ovalbumin , bronchoalveolar lavage , antagonist , lipopolysaccharide , immunology , pharmacology , receptor antagonist , tlr4 , chemistry , receptor , medicine , immune system , lung , biochemistry
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.