Osthole inhibits ovalbumin (OVA) induced asthma through regulating TLR9/JNK pathway

Abstract

Osthole is an active coumarin extracted from Cnidiummonnieri(L.) Cusson, a traditional Chinese herb which possesses multiple pharmacological activities. Asthma is a long term disease characterized by chronic airway inflammation and hyper-responsiveness. Worldwide, around 339 million people are reported to be suffering from asthma. Coumarinosthole has been known to exhibitanti-inflammatory and antiallergic activities. Here, we investigated mechanisms underlying the protective effects of osthole in ovalbumin (OVA)induced asthmatic mice. A total 40 C57BL/6 male mice were used as experimental model animals. The results showed that osthole treatment significantly reduces OVA-induced elevated levels of serum IgE and inflammatory cytokines (IL-4, IL-5, IL-6, IL-13) except IL-10 in bronchoalveolar lavage fluid (BALF), and decreased the recruitment of inflammatory cells in BALF. The CCK-8 assay was performed to examine the viability of cells. The enzymelinked immunosorbent assay (ELISA) was used to determine the expression of inflammatory factors. Western blot analysis was conducted to examine TLR9 and JNK protein expression. Results showed that osthole significantly inhibits the recruitment of inflammatory cells and Th1/Th2 cytokines expression in BALF and airway hyper-responsiveness. Furthermore, osthole attenuated upregulation of systemic immunoglobulin production derived from OVA sensitization. Results also suggest that osthole can reverse the imbalance of Thlfrh2 in asthma, thus alleviating the symptoms of asthma to a certain extent. In conclusion, the study demonstrated that osthole, activecoumarin extract ofCnidiummonnieri, attenuated the allergic airway inflammationvia inhibition of TLR9/JNK pathway in mice model indicating that it could be a potential therapeutic target for asthma.