Airway relaxation mechanisms and structural basis of osthole for improving lung function in asthma

signaling in airway smooth muscle cells that eventually triggered cAMP/PKA-dependent relaxation of airways. The crystal structure of the PDE4D complexed with osthole revealed that osthole bound to the catalytic site to prevent cAMP binding and hydrolysis. Together, our studies elucidate a specific molecular target and mechanism by which osthole induces airway relaxation. Identification of osthole binding sites on PDE4D will guide further development of bronchodilators that are not subject to tachyphylaxis and would thus avoid β2-adrenoceptor agonist resistance.