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

Abstract

Toll-like receptor-4 (TLR4) is a key component of the innate immune system and activation of TLR4 signaling has a significant role in the pathogenesis of asthma. Therefore, our objective was to identify the natural TLR4 antagonist and evaluate its activity in experimentally induced asthma. Soya lecithin origin phosphatidylcholine (soya PC) was identified as a natural TLR4 antagonist by computational study. Based on the computational study, TLR4 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 (BALf) and histological examinations. The computational study indicated that TLR4 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 BALf 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 TLR4 antagonist activity and linoleic acid composition.

Bacterially Delivered miRNA-Mediated Toll-like Receptor 8 Gene Silencing for Combined Therapy in a Murine Model of Atopic Dermatitis: Therapeutic Effect of miRTLR8 in AD

“…In order to clinically manipulate TLR, it should be altered through receptor antagonists, receptor agonists or single transduction inhibitors [ 17 ]. Currently, a TLR4 antagonist initially developed for sepsis therapy is being clinically tested for the treatment of allergic diseases [ 18 , 19 ].…”

Using high-throughput metabolomics to discover perturbed metabolic pathways and biomarkers of allergic rhinitis as potential targets to reveal the effects and mechanism of geniposide

“…18,19 Currently, the two most common allergens used are OVA and TDI. 20 TDI has a strong non-specic stimulatory effect and, as a toxic low-molecular chemical agent, poses certain hazards to personnel while being handled, while OVA does not display these drawbacks and has been successfully used in many studies. 21 Because intraperitoneal and subcutaneous injections of allergens are not consistent with the natural law of morbidity, the method of sensitization should be limited to local administration.…”

Acute and 28-days subacute toxicity studies of Gαq-RGS2 signaling inhibitor

“…All the specimens were sent for section and staining with hematoxylin and eosin dye. Images of selected sections were captured at original (100x) magnifications using a zoom digital camera (MLX, Magnus, China) [ 19 , 21 ].…”