| Summary: | 博士 === 國立陽明大學 === 傳統醫藥研究所 === 100 === Asthma is a chronic inflammatory disease with the characteristics of airway inflammation, airway hyperresponsiveness, and airway mucus production. Activation of NF-B is highly associated with the pathogenesis of asthma, and previous studies reveal that NF-κB is a promising molecular target in the treatment of asthma. Natural products present in food or Chinese medicinal herbs may have potential on inhibition of NF-κB activity and attenuation of allergic asthma. In this study, I first screened for compounds isolated from food and traditional Chinese medicinal herbs on the suppressive effects of NF-κB activity. Fisetin, a flavonoid compound commonly present in fruits and vegetables, can exert anti-inflammatory activities via inhibition of NF-κB-signaling pathway. I further evaluated the anti-asthma activity of fisetin and its possible molecular mechanisms. Fisetin attenuated lung inflammation, goblet cell hyperplasia and airway hyperresponsiveness in ovalbumin-induced asthma, and decreased eosinophils and lymphocytes in bronchoalveolar lavage fluid. Fisetin treatment reduced expressions of the key initiators of allergic airway inflammation (eotaxin-1 and thymic stromal lymphopoietin), Th2-associated cytokines (IL-4, IL-5, and IL-13) in lungs, and Th2-predominant transcription factor gata-3 and cytokines in thoracic lymph node cells and splenocytes. Notably, fisetin treatment impaired NF-κB activation in ovalbumin-stimulated lung tissues and TNF-α-stimulated bronchial epithelial cells. Collectively, the data demonstrate the beneficial effects of fisetin in the amelioration of asthmatic phenotypes. The anti-asthma activity of fisetin is associated with reduction of Th2 responses as well as suppression of NF-κB activity and its downstream cytokines and chemokines. I also demonstrated in this study that puerarin suppressed PHA-stimulated IL-2 expression and inhibited the ERK1/2-c-Fos signaling pathway induced by PHA-stimulation in Jurkat cells. Puerarin may have potential in immunosuppression and in asthma treatment.
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