Santonin attenuates Ovalbumin-induced airway inflammation by inhibiting IL-4/IL-13 signaling

Airway inflammation is a hallmark of asthma and is characterised by swelling of the lung airways and excessive mucus production. Enhanced oxidative stress, immune cell activation, increased specific IgE antibodies and Th2-mediated inflammation are the underlying causes of asthma. Santonin (SANT), a sesquiterpene lactone, exhibits therapeutic potential for the treatment of inflammatory diseases. It is a compound of interest due to its potential therapeutic benefits against allergic airway inflammation, a condition for which traditional therapies have limited efficacy and serious side effects. The study aimed to assess the impact of Santonin on ovalbumin (OVA)-induced allergic airway inflammation in a mouse model, focusing on allergy symptoms, immune response, oxidative stress, and underlying molecular pathways. Male mice were sensitised with OVA and alum, and then nebulisation was used to induce airway inflammation. The mice were administered SANT at doses of 10, 20, and 40 mg/kg to assess its therapeutic effect on airway inflammation. Allergic symptoms like rhinorrhoea and serum IgE levels of inflammatory cells in blood and BLAF are measured. Furthermore, oxidative stress and gene expression were targeted using RT-qPCR. Histopathological changes and DNA damage were performed using a comet assay. SANT alleviated allergic symptoms such as rhinorrhoea. It enhanced the levels of antioxidant enzymes (GST, GSH, CAT) and decreased oxidative stress markers (MDA and NO), improved disease-induced DNA damage, and decreased IgE levels in BALF. Lung histopathology showed reduced collagen deposition and improved inflammatory scores. The qRT-PCR results demonstrated that Santonin inhibits the IL-4/IL-13 pathway in OVA-induced airway inflammation. The findings suggest that by lowering IgE levels, reducing oxidative stress, and altering immunological pathways, specifically the IL-4/IL-13 pathway-Santonin can be used as a therapeutic drug to treat allergic airway inflammation.