RESUMO
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-κB pathway and Wnt/ß-catenin pathway, and overexpressing TLR4 or activating the Wnt/ß-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-κB pathway and Wnt/ß-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.
RESUMO
OBJECTIVE： To observe the improvement effects of ethanol extract of the root of Anacyclus pyrethrum （EEAP） on cough variant asthma （CVA） model rats. METHODS： Male SD rats were randomly divided into control group， model group， prednisone acetate group （positive control， 250 mg/kg）， EEAP low-dose， medium-dose and high-dose groups （160， 320， 640 mg/kg， by the weight of EEAP）， with 10 rats in each group. Except for control group， other group was given 1 mg/mL ovalbumin （OVA）-Freunds adjuvant complete solution subcutaneously， and aerosol inhalation of 1％ OVA-normal saline （once a day， 20 min each time， 15 d） to induce CVA. After last inhalation， control group and model group were given constant volume of water intragastrically； administration groups were given relevant medicine intragastrically， once a day， for consecutive 30 d. General symptoms of rats were observed in each group during experiment. The airway sensitivity of rats in each group was investigated by capsaicin cough provocation test， and the cough times were recorded. The contents of SOD and TNF-α in serum were determined by ELISA. The morphological characteristics of lung tissue were observed by HE staining. The number of eosinophils and leucocytes in alveolar lavage fluid was recorded by Rayleigh staining. RESULTS： Rats in the control group breathed smoothly， responded quickly and had glossy coat. The rest of the groups showed restlessness， cough， shortness of breath and other symptoms after antigen stimulation. Compared with control group， the congestion and edema of bronchial wall and infiltration of inflammatory cells in the lung tissue were observed in model group； the cough times increased significantly； serum content of TNF-α， eosinophil and leukocyte counts in alveolar lavage fluid increased significantly， and serum content of SOD decreased significantly （P＜0.05）. After treatment， above symptoms of rats were alleviated to varying degrees in administration groups， and the cough times were significantly reduced； the serum contents of TNF-α as well as eosinophil and leukocyte counts in alveolar lavage fluid were significantly reduced； the serum contents of SOD was increased significantly， but the cough times of EEAP groups were significantly higher than that of prednisone acetate group （P＜0.05）. CONCLUSIONS： EEAP may show the anti-inflammatory and antiasthmatic effects by inhibiting the secretion of TNF-α， increasing the content of SOD and inhibiting inflammatory cell infiltration.
