Ethanol Extract of Anacyclus pyrethrum Root Ameliorates Cough-Variant Asthma Through the TLR4/NF-B Pathway and Wnt/-Catenin Pathway

Cough-variant asthma (CVA) has been recognized as the initial stage or pre-asthmatic state of classic asthma, which characterized by cough as the primary clinical presentation. Inhaled glucocorticoids, oral leukotriene receptor antagonists and antihistamines are the clinical treatments, but their efficacy is not satisfactory. Some traditional Chinese medicine (TCM) has been reported to have certain advantages in the treatment of CVA, but the underlying molecular mechanisms are still unclear. Recent research has indicated that Anacyclus pyerhrurm (L) DC. is commonly used in the treatment of human diseases. The aim of our study was to evaluate the anti-inflammatory and anti-oxidative mechanism of the ethanol extract of Anacyclus pyrethrum (L) DC. root (EEAP) in a model of CVA. In our study, we indicated that EEAP ameliorated CVA by reducing cough frequency and inflammatory effect and oxidative stress in an in vivo rat model of CVA. In addition, EEAP ameliorated LPS-induced cell apoptosis and regulated inflammatory effect and oxidative stress in vitro. Mechanistically, EEAP exerted anti-inflammatory effects through regulating the TLR4/NF-kappa B pathway and Wnt/beta-catenin pathway, and overexpressing TLR4 or activating the Wnt/beta-catenin pathway by SKL2001 reversed EEAP-exerted effects in LPS-exposed BEAS-2B and 16-HBE cells. In conclusion, EEAP attenuated cell apoptosis, inflammation and oxidative stress through restraining the TLR4/NF-kappa B pathway and Wnt/beta-catenin pathway in CVA, which shown that EEAP might be a promising therapeutic agent for CVA and may provide a theoretical basis for clinical treatment with CVA patients.